Review Article

影响内生植物代谢产物的因素:产生代谢产物的生物技术方法

卷 27, 期 11, 2020

页: [1855 - 1873] 页: 19

弟呕挨: 10.2174/0929867326666190626154421

价格: $65

摘要

自1980年以来,人们对磷菌,镰刀菌,粉虱和曲霉的内生属的许多物种和不同菌株进行了研究,因为它们具有产生宿主植物中发现的药用化合物的能力。 经过优化后,这些药物中的一些例如紫杉醇,布雷菲德菌素A,喜树碱和鬼臼毒素正在大量生产。 然而,真菌内生菌产生宿主样药物的潜力仍未得到充分探索。

关键词: 内生菌,次生代谢产物,抗癌药,药物,生物技术,药用化合物。

« Previous
[1]
Strohl, W.R. The role of natural products in a modern drug discovery program. Drug Discov. Today, 2000, 5(2), 39-41.
[http://dx.doi.org/10.1016/S1359-6446(99)01443-9] [PMID: 10652450]
[2]
Taylor, L. Plant based drugs and medicines., http://www.rain-tree.com2017.
[3]
Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J. Nat. Prod., 2012, 75(3), 311-335.
[http://dx.doi.org/10.1021/np200906s] [PMID: 22316239]
[4]
Patridge, E.; Gareiss, P.; Kinch, M.S.; Hoyer, D. An analysis of FDA-approved drugs: natural products and their derivatives. Drug Discov. Today, 2016, 21(2), 204-207.
[http://dx.doi.org/10.1016/j.drudis.2015.01.009] [PMID: 25617672]
[5]
Schiff, P.L. Opium and its alkaloids. Am. J. Pharm. Educ., 2002, 66(2), 188-196.
[6]
Wang, J.; Li, J.L.; Li, J.; Li, J.X.; Liu, S.J.; Huang, L.Q.; Gao, W.Y. Production of active compounds in medicinal plants: from plant tissue culture to biosynthesis. Chin. Herb. Med., 2017, 9(2), 115-125.
[http://dx.doi.org/10.1016/S1674-6384(17)60085-6]
[7]
Wilson, D. Endophyte: the evolution of a term, and clarification of its use and definition. Oikos, 1995, 73(2), 274-276.
[http://dx.doi.org/10.2307/3545919]
[8]
Bacon, C.W.; White, J.F. Microbial Endophytes, 2000.
[9]
Schulz, B.; Boyle, C. What are Endophytes?Microbial Root Endophytes; Soil Biology, 2006.
[10]
Dutta, D.; Puzari, K.C.; Gogoi, R.; Dutta, P. Endophytes: Exploitation as a tool in plant protection. Braz. Arch. Biol. Technol., 2014, 57(5), 621-629.
[http://dx.doi.org/10.1590/S1516-8913201402043]
[11]
Strobel, G.; Daisy, B. Bioprospecting for microbial endophytes and their natural products. Microbiol. Mol. Biol. Rev., 2003, 67(4), 491-502.
[http://dx.doi.org/10.1128/MMBR.67.4.491-502.2003] [PMID: 14665674]
[12]
Nalini, M.S.; Prakash, H.S. Diversity and bioprospecting of actinomycete endophytes from the medicinal plants. Lett. Appl. Microbiol., 2017, 64(4), 261-270.
[http://dx.doi.org/10.1111/lam.12718] [PMID: 28107573]
[13]
Zhang, H.W.; Song, Y.C.; Tan, R.X. Biology and chemistry of endophytes. Nat. Prod. Rep., 2006, 23(5), 753-771.
[http://dx.doi.org/10.1039/b609472b] [PMID: 17003908]
[14]
Clay, K.; Schardl, C. Evolutionary origins and ecological consequences of endophyte symbiosis with grasses. Am. Nat., 2002, 160(S4)(Suppl. 4), S99-S127.
[http://dx.doi.org/10.1086/342161] [PMID: 18707456]
[15]
Wang, Y.; Dai, C. Endophytes: A potential resource for biosynthesis, biotransformation, and biodegradation. Ann. Microbiol., 2011, 61(2), 207-215.
[http://dx.doi.org/10.1007/s13213-010-0120-6]
[16]
Schulz, B.; Boyle, C.; Draeger, S.; Römmert, A.; Krohn, K. Endophytic fungi: a source of novel biologically active secondary metabolites. Mycol. Res., 2002, 106(9), 996-1004.
[http://dx.doi.org/10.1017/S0953756202006342]
[17]
Hansson, D. 2013.
[18]
Firáková, S.; Šturdíková, M.; Múčková, M. Bioactive secondary metabolites produced by microorganisms associated with plants. Biologia, 2007, 62(3), 251-257.
[http://dx.doi.org/10.2478/s11756-007-0044-1]
[19]
Kharwar, R.N.; Mishra, A.; Gond, S.K.; Stierle, A.; Stierle, D. Anticancer compounds derived from fungal endophytes: their importance and future challenges. Nat. Prod. Rep., 2011, 28(7), 1208-1228.
[http://dx.doi.org/10.1039/c1np00008j] [PMID: 21455524]
[20]
Chen, L.; Zhang, Q.Y.; Jia, M.; Ming, Q.L.; Yue, W.; Rahman, K.; Qin, L.P.; Han, T. Endophytic fungi with antitumor activities: Their occurrence and anticancer compounds. Crit. Rev. Microbiol., 2016, 42(3), 454-473.
[http://dx.doi.org/10.3109/1040841X.2014.959892] [PMID: 25343583]
[21]
Andrés, M.F.; Diaz, C.E.; Giménez, C.; Cabrera, R.; González-Coloma, A. Endophytic fungi as novel sources of biopesticides: the Macaronesian Laurel forest, a case study. Phytochem. Rev., 2017, 16(5), 1009-1022.
[http://dx.doi.org/10.1007/s11101-017-9514-4]
[22]
González-Coloma, A.; Cosoveanu, A.; Cabrera, R.; Giménez, C.; Kaushik, N. Endophytic Fungi and Their Bioprospection; Fungi. Applications and Management Strategies, 2016.
[23]
Germaine, K.; Keogh, E.; Garcia-Cabellos, G.; Borremans, B.; Lelie, D.; Barac, T.; Oeyen, L.; Vangronsveld, J.; Moore, F.P.; Moore, E.R.; Campbell, C.D.; Ryan, D.; Dowling, D.N. Colonisation of poplar trees by gfp expressing bacterial endophytes. FEMS Microbiol. Ecol., 2004, 48(1), 109-118.
[http://dx.doi.org/10.1016/j.femsec.2003.12.009] [PMID: 19712436]
[24]
Guo, B.; Wang, Y.; Sun, X.; Tang, K. Bioactive natural products from endophytes: a review. Prikl. Biokhim. Mikrobiol., 2008, 44(2), 153-158.
[PMID: 18669256]
[25]
Jennewein, S.; Rithner, C.D.; Williams, R.M.; Croteau, R.B. Taxol biosynthesis: taxane 13 alpha-hydroxylase is a cytochrome P450-dependent monooxygenase. Proc. Natl. Acad. Sci. USA, 2001, 98(24), 13595-13600.
[http://dx.doi.org/10.1073/pnas.251539398] [PMID: 11707604]
[26]
Chandra, S. Endophytic fungi: novel sources of anticancer lead molecules. Appl. Microbiol. Biotechnol., 2012, 95(1), 47-59.
[http://dx.doi.org/10.1007/s00253-012-4128-7] [PMID: 22622838]
[27]
Bömke, C.; Tudzynski, B. Diversity, regulation, and evolution of the gibberellin biosynthetic pathway in fungi compared to plants and bacteria. Phytochemistry, 2009, 70(15-16), 1876-1893.
[http://dx.doi.org/10.1016/j.phytochem.2009.05.020] [PMID: 19560174]
[28]
Heinig, U.; Scholz, S.; Jennewein, S. Getting to the bottom of Taxol biosynthesis by fungi. Fungal Divers., 2013, 60(1), 161-170.
[http://dx.doi.org/10.1007/s13225-013-0228-7]
[29]
Alvin, A.; Miller, K.I.; Neilan, B.A. Exploring the potential of endophytes from medicinal plants as sources of antimycobacterial compounds. Microbiol. Res., 2014, 169(7-8), 483-495.
[http://dx.doi.org/10.1016/j.micres.2013.12.009] [PMID: 24582778]
[31]
Martinez-Klimova, E.; Rodríguez-Peña, K.; Sánchez, S. Endophytes as sources of antibiotics. Biochem. Pharmacol., 2017, 134, 1-17.
[http://dx.doi.org/10.1016/j.bcp.2016.10.010] [PMID: 27984002]
[32]
Weber, R.W.; Stenger, E.; Meffert, A.; Hahn, M. Brefeldin A production by Phoma medicaginis in dead pre-colonized plant tissue: a strategy for habitat conquest? Mycol. Res., 2004, 108(Pt 6), 662-671.
[http://dx.doi.org/10.1017/S0953756204000243] [PMID: 15323249]
[33]
Hussain, H.; Kock, I.; Al-Harrasi, A.; Al-Rawahi, A.; Abbas, G.; Green, I.R.; Shah, A.; Badshah, A.; Saleem, M.; Draeger, S.; Schulz, B.; Krohn, K. Antimicrobial chemical constituents from endophytic fungus Phoma sp. Asian Pac. J. Trop. Dis., 2014, 7(9), 699-702.
[http://dx.doi.org/10.1016/S1995-7645(14)60119-X]
[34]
Weber, D.; Sterner, O.; Anke, T.; Gorzalczancy, S.; Martino, V.; Acevedo, C. Phomol, a new antiinflammatory metabolite from an endophyte of the medicinal plant Erythrina crista-galli. J. Antibiot. (Tokyo), 2004, 57(9), 559-563.
[http://dx.doi.org/10.7164/antibiotics.57.559] [PMID: 15580955]
[35]
Horn, W.S.; Simmonds, M.S.J.; Schwartz, R.E.; Blaney, W.M. Phomopsichalasin, a novel antimicrobial agent from an endophytic Phomopsis sp. Tetrahedron, 1995, 51(14), 3969-3978.
[http://dx.doi.org/10.1016/0040-4020(95)00139-Y]
[36]
Jouda, J.B.; Tamokou, J.D.; Mbazoa, C.D.; Douala-Meli, C.; Sarkar, P.; Bag, P.K.; Wandji, J. Antibacterial and cytotoxic cytochalasins from the endophytic fungus Phomopsis sp. harbored in Garcinia kola (Heckel) nut. BMC Complement. Altern. Med., 2016, 16(1), 462.
[http://dx.doi.org/10.1186/s12906-016-1454-9] [PMID: 27842536]
[37]
Castillo, U.; Harper, J.K.; Strobel, G.A.; Sears, J.; Alesi, K.; Ford, E.; Lin, J.; Hunter, M.; Maranta, M.; Ge, H.; Yaver, D.; Jensen, J.B.; Porter, H.; Robison, R.; Millar, D.; Hess, W.M.; Condron, M.; Teplow, D. Kakadumycins, novel antibiotics from Streptomyces sp NRRL 30566, an endophyte of Grevillea pteridifolia. FEMS Microbiol. Lett., 2003, 224(2), 183-190.
[http://dx.doi.org/10.1016/S0378-1097(03)00426-9] [PMID: 12892881]
[38]
Ezra, D.; Castillo, U.F.; Strobel, G.A.; Hess, W.M.; Porter, H.; Jensen, J.B.; Condron, M.A.M.; Teplow, D.B.; Sears, J.; Maranta, M.; Hunter, M.; Weber, B.; Yaver, D. Coronamycins, peptide antibiotics produced by a verticillate Streptomyces sp. (MSU-2110) endophytic on Monstera sp. Microbiology, 2004, 150(Pt 4), 785-793.
[http://dx.doi.org/10.1099/mic.0.26645-0] [PMID: 15073289]
[39]
Castillo, U.F.; Strobel, G.A.; Ford, E.J.; Hess, W.M.; Porter, H.; Jensen, J.B.; Albert, H.; Robison, R.; Condron, M.A.M.; Teplow, D.B.; Stevens, D.; Yaver, D. Munumbicins, wide-spectrum antibiotics produced by Streptomyces NRRL 30562, endophytic on Kennedia nigriscans. Microbiology, 2002, 148(Pt 9), 2675-2685.
[http://dx.doi.org/10.1099/00221287-148-9-2675] [PMID: 12213914]
[40]
Liu, J.Y.; Song, Y.C.; Zhang, Z.; Wang, L.; Guo, Z.J.; Zou, W.X.; Tan, R.X. Aspergillus fumigatus CY018, an endophytic fungus in Cynodon dactylon as a versatile producer of new and bioactive metabolites. J. Biotechnol., 2004, 114(3), 279-287.
[http://dx.doi.org/10.1016/j.jbiotec.2004.07.008] [PMID: 15522437]
[41]
Geris dos Santos, R.M.; Rodrigues-Fo, E. Meroterpenes from Penicillium sp found in association with Melia azedarach. Phytochemistry, 2002, 61(8), 907-912.
[http://dx.doi.org/10.1016/S0031-9422(02)00379-5] [PMID: 12453515]
[42]
Singh, B.; Zink, D.; Guan, Z.; Collado, J.; Pelaez, F.; Felock, P.; Hazuda, D. Isolation, structure, and HIV‐1 integrase inhibitory activity of Xanthoviridicatin E and F, two novel fungal metabolites produced by Penicillium chrysogenum. Helv. Chim. Acta, 2003, 86(10), 3380-3385.
[http://dx.doi.org/10.1002/hlca.200390281]
[43]
Lu, H.; Zou, W.X.; Meng, J.C.; Hu, J.; Tan, R.X. New bioactive metabolites produced by Colletotrichum sp., an endophytic fungus in Artemisia annua. Plant Sci., 2000, 151(1), 67-73.
[http://dx.doi.org/10.1016/S0168-9452(99)00199-5]
[44]
Park, J.H.; Choi, G.J.; Lee, H.B.; Kim, K.M.; Jung, H.S.; Lee, S.W.; Kim, J.C. Griseofulvin from Xylaria sp. Strain F0010, an endophytic fungus of Abies holophylla and its antifungal activity against plant pathogenic fungi. J. Microbiol. Biotechnol., 2005, 15(1), 112-117.
[45]
Ma, Y.M.; Li, Y.; Liu, J.Y.; Song, Y.C.; Tan, R.X. Anti-Helicobacter pylori metabolites from Rhizoctonia sp. Cy064, an endophytic fungus in Cynodon dactylon. Fitoterapia, 2004, 75(5), 451-456.
[http://dx.doi.org/10.1016/j.fitote.2004.03.007] [PMID: 15261382]
[47]
Wagenaar, M.M.; Clardy, J. Dicerandrols, new antibiotic and cytotoxic dimers produced by the fungus Phomopsis longicolla isolated from an endangered mint. J. Nat. Prod., 2001, 64(8), 1006-1009.
[http://dx.doi.org/10.1021/np010020u] [PMID: 11520215]
[48]
Bunyapaiboonsri, T.; Yoiprommarat, S.; Srikitikulchai, P.; Srichomthong, K.; Lumyong, S. Oblongolides from the endophytic fungus Phomopsis sp. BCC 9789. J. Nat. Prod., 2010, 73(1), 55-59.
[http://dx.doi.org/10.1021/np900650c] [PMID: 20038128]
[49]
Isaka, M.; Jaturapat, A.; Rukseree, K.; Danwisetkanjana, K.; Tanticharoen, M.; Thebtaranonth, Y. Phomoxanthones A and B, novel xanthone dimers from the endophytic fungus Phomopsis species. J. Nat. Prod., 2001, 64(8), 1015-1018.
[http://dx.doi.org/10.1021/np010006h] [PMID: 11520217]
[50]
Strobel, G.; Yang, X.; Sears, J.; Kramer, R.; Sidhu, R.S.; Hess, W.M.; Young, B. Taxol from Pestalotiopsis microspora, an endophytic fungus of Taxus wallachiana. Microbiology, 1996, 142(Pt 2), 435-440.
[http://dx.doi.org/10.1099/13500872-142-2-435] [PMID: 8932715]
[51]
Li, J.Y.; Harper, J.K.; Grant, D.M.; Tombe, B.O.; Bashyal, B.; Hess, W.M.; Strobel, G.A. Ambuic acid, a highly functionalized cyclohexenone with antifungal activity from Pestalotiopsis spp. and Monochaetia sp. Phytochemistry, 2001, 56(5), 463-468.
[http://dx.doi.org/10.1016/S0031-9422(00)00408-8] [PMID: 11261579]
[52]
Zhan, J.; Burns, A.M.; Liu, M.X.; Faeth, S.H.; Gunatilaka, A.A.L. Search for cell motility and angiogenesis inhibitors with potential anticancer activity: beauvericin and other constituents of two endophytic strains of Fusarium oxysporum. J. Nat. Prod., 2007, 70(2), 227-232.
[http://dx.doi.org/10.1021/np060394t] [PMID: 17286429]
[53]
Nadeem, M. Fusarium solani, P1, a new endophytic podophyllotoxin-producing fungus from roots of Podophyllum hexandrum. Afr. J. Microbiol. Res., 2012, 6(10), 2493-2499.
[54]
Lin, Z.; Zhu, T.; Fang, Y.; Gu, Q.; Zhu, W. Polyketides from Penicillium sp. JP-1, an endophytic fungus associated with the mangrove plant Aegiceras corniculatum. Phytochemistry, 2008, 69(5), 1273-1278.
[http://dx.doi.org/10.1016/j.phytochem.2007.10.030] [PMID: 18067932]
[55]
Aly, A.H.; Edrada-Ebel, R.; Indriani, I.D.; Wray, V.; Müller, W.E.G.; Totzke, F.; Zirrgiebel, U.; Schächtele, C.; Kubbutat, M.H.; Lin, W.H.; Proksch, P.; Ebel, R. Cytotoxic metabolites from the fungal endophyte Alternaria sp. and their subsequent detection in its host plant Polygonum senegalense. J. Nat. Prod., 2008, 71(6), 972-980.
[http://dx.doi.org/10.1021/np070447m] [PMID: 18494522]
[56]
Huang, C.H.; Pan, J.H.; Chen, B.; Yu, M.; Huang, H.B.; Zhu, X.; Lu, Y.J.; She, Z.G.; Lin, Y.C. Three bianthraquinone derivatives from the mangrove endophytic fungus Alternaria sp. ZJ9-6B from the South China Sea. Mar. Drugs, 2011, 9(5), 832-843.
[http://dx.doi.org/10.3390/md9050832] [PMID: 21673892]
[57]
Song, Y.C.; Li, H.; Ye, Y.H.; Shan, C.Y.; Yang, Y.M.; Tan, R.X. Endophytic naphthopyrone metabolites are co-inhibitors of xanthine oxidase, SW1116 cell and some microbial growths. FEMS Microbiol. Lett., 2004, 241(1), 67-72.
[http://dx.doi.org/10.1016/j.femsle.2004.10.005] [PMID: 15556711]
[58]
Ge, H.M.; Yu, Z.G.; Zhang, J.; Wu, J.H.; Tan, R.X. Bioactive alkaloids from endophytic Aspergillus fumigatus. J. Nat. Prod., 2009, 72(4), 753-755.
[http://dx.doi.org/10.1021/np800700e] [PMID: 19256529]
[59]
Stierle, A.A.; Stierle, D.B.; Bugni, T. Sequoiatones A and B: novel antitumor metabolites isolated from a redwood endophyte. J. Org. Chem., 1999, 64(15), 5479-5484.
[http://dx.doi.org/10.1021/jo990277l] [PMID: 11674610]
[60]
Cragg, G.M.; Newman, D.J. Plants as a source of anti-cancer agents. J. Ethnopharmacol., 2005, 100(1-2), 72-79.
[http://dx.doi.org/10.1016/j.jep.2005.05.011] [PMID: 16009521]
[61]
Cragg, G.M.; Newman, D.J.; Snader, K.M. Natural products in drug discovery and development. J. Nat. Prod., 1997, 60(1), 52-60.
[http://dx.doi.org/10.1021/np9604893] [PMID: 9014353]
[62]
Kumar, A.; Ahmad, A. Biotransformation of vinblastine to vincristine by the endophytic fungus Fusarium oxysporum isolated from Catharanthus roseus. Biocatal. Biotransform., 2013, 31(2), 89-93.
[http://dx.doi.org/10.3109/10242422.2013.776544]
[63]
Malik, S.; Cusidó, R.M.; Mirjalili, M.H.; Moyano, E.; Palazón, J.; Bonfill, M. Production of the anticancer drug taxol in Taxus baccata suspension cultures: a review. Process Biochem., 2011, 46(1), 23-34.
[http://dx.doi.org/10.1016/j.procbio.2010.09.004]
[64]
Cragg, G.M. Paclitaxel (Taxol): a success story with valuable lessons for natural product drug discovery and development. Med. Res. Rev., 1998, 18(5), 315-331.
[http://dx.doi.org/10.1002/(SICI)1098-1128(199809)18:5<315:AID-MED3>3.0.CO;2-W] [PMID: 9735872]
[65]
Schiff, P.B.; Horwitz, S.B. Taxol stabilizes microtubules in mouse fibroblast cells. Proc. Natl. Acad. Sci. USA, 1980, 77(3), 1561-1565.
[http://dx.doi.org/10.1073/pnas.77.3.1561] [PMID: 6103535]
[66]
Howat, S.; Park, B.; Oh, I.S.; Jin, Y.W.; Lee, E.K.; Loake, G.J. Paclitaxel: biosynthesis, production and future prospects. N. Biotechnol., 2014, 31(3), 242-245.
[http://dx.doi.org/10.1016/j.nbt.2014.02.010] [PMID: 24614567]
[67]
Holton, R.A.; Somoza, C.; Kim, B.H.; Liang, F.; Biediger, J.R.; Boatman, D.P.; Shindo, M.; Smith, C.C.; Kim, S.; Nadizadeh, H.; Suziki, Y.; Tao, C.; Vu, P.; Tang, S.; Zhang, P.; Murthi, K.; Gentile, L.; Liu, J. First total synthesis of taxol. 1. Functionalization of the B ring. J. Am. Chem. Soc., 1994, 116(4), 1597-1598.
[http://dx.doi.org/10.1021/ja00083a066]
[68]
Nicolaou, K.C.; Yang, Z.; Liu, J.J.; Ueno, H.; Nantermet, P.G.; Guy, R.K.; Claiborne, C.F.; Renaud, J.; Couladouros, E.A.; Paulvannan, K. Total synthesis of taxol. Nature, 1994, 367(6464), 630-634.
[http://dx.doi.org/10.1038/367630a0] [PMID: 7906395]
[69]
Collin, H.A. Secondary product formation in plant tissue cultures. J. Plant Growth Regul., 2001, 34(1), 119-134.
[http://dx.doi.org/10.1023/A:1013374417961]
[70]
Hezari, M.; Ketchum, R.E.B.; Gibson, D.M.; Croteau, R. Taxol production and taxadiene synthase activity in Taxus canadensis cell suspension cultures. Arch. Biochem. Biophys., 1997, 337(2), 185-190.
[http://dx.doi.org/10.1006/abbi.1996.9772] [PMID: 9016812]
[71]
Roberts, S.C. Production and engineering of terpenoids in plant cell culture. Nat. Chem. Biol., 2007, 3(7), 387-395.
[http://dx.doi.org/10.1038/nchembio.2007.8] [PMID: 17576426]
[72]
Stierle, A.; Strobel, G.; Stierle, D. Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science, 1993, 260(5105), 214-216.
[http://dx.doi.org/10.1126/science.8097061] [PMID: 8097061]
[73]
Zaiyou, J.; Li, M.; Xiqiao, H. An endophytic fungus efficiently producing paclitaxel isolated from Taxus wallichiana var. mairei. Medicine (Baltimore), 2017, 96(27)e7406
[http://dx.doi.org/10.1097/MD.0000000000007406] [PMID: 28682896]
[74]
Flores-Bustamante, Z.R.; Rivera-Orduña, F.N.; Martínez-Cárdenas, A.; Flores-Cotera, L.B. Microbial paclitaxel: advances and perspectives. J. Antibiot. (Tokyo), 2010, 63(8), 460-467.
[http://dx.doi.org/10.1038/ja.2010.83] [PMID: 20628412]
[75]
Shankar, N.A. Developments in taxol production through endophytic fungal biotechnology: a review. Orient. Pharm. Exp. Med., 2019, 19, 1-13.
[http://dx.doi.org/10.1007/s13596-018-0352-8]
[76]
Wink, M.; Alfermann, A.; Franke, R.; Wetterauer, B.; Distl, M.; Windhövel, J.; Krohn, O.; Fuss, E.; Garden, H.; Mohagheghzadeh, A.; Wildi, E.; Ripplinger, P. Sustainable bioproduction of phytochemicals by plant in vitro cultures: anticancer agents. Plant Genet. Resour., 2005, 3(2), 90-100.
[http://dx.doi.org/10.1079/PGR200575]
[77]
Expósito, O.; Bonfill, M.; Moyano, E.; Onrubia, M.; Mirjalili, M.H.; Cusidó, R.M.; Palazón, J. Biotechnological production of taxol and related taxoids: current state and prospects. Anticancer. Agents Med. Chem., 2009, 9(1), 109-121.
[http://dx.doi.org/10.2174/187152009787047761] [PMID: 19149486]
[78]
Ji, Y.; Bi, J.N.; Yan, B.; Zhu, X.D. [Taxol-producing fungi: a new approach to industrial production of taxol]. Sheng Wu Gong Cheng Xue Bao, 2006, 22(1), 1-6.
[http://dx.doi.org/10.1016/S1872-2075(06)60001-0] [PMID: 16572833]
[80]
Loike, J.D.; Horwitz, S.B. Effects of podophyllotoxin and VP-16-213 on microtubule assembly in vitro and nucleoside transport in HeLa cells. Biochemistry, 1976, 15(25), 5435-5443.
[http://dx.doi.org/10.1021/bi00670a003] [PMID: 999818]
[81]
Horwitz, S.B.; Loike, J.D. A comparison of the mechanisms of action of VP-16-213 and podophyllotoxin. Lloydia, 1977, 40(1), 82-89.
[PMID: 875640]
[82]
Minocha, A.; Long, B.H. Inhibition of the DNA catenation activity of type II topoisomerase by VP16-213 and VM26. Biochem. Biophys. Res. Commun., 1984, 122(1), 165-170.
[http://dx.doi.org/10.1016/0006-291X(84)90454-6] [PMID: 6331440]
[83]
Yousefzadi, M.; Sharifi, M.; Behmanesh, M.; Moyano, E.; Bonfill, M.; Cusido, R.M.; Palazon, J. Podophyllotoxin: current approaches to its biotechnological production and future challenges. Eng. Life Sci., 2010, 10(4), 281-292.
[http://dx.doi.org/10.1002/elsc.201000027]
[84]
Yousefzadi, M.; Sharifi, M.; Behmanesh, M.; Ghasempour, A.; Moyano, E.; Palazon, J. Salicylic acid improves podophyllotoxin production in cell cultures of Linum album by increasing the expression of genes related with its biosynthesis. Biotechnol. Lett., 2010, 32(11), 1739-1743.
[http://dx.doi.org/10.1007/s10529-010-0343-4] [PMID: 20607358]
[85]
Kumar, P.; Pal, T.; Sharma, N.; Kumar, V.; Sood, H.; Chauhan, R.S. Expression analysis of biosynthetic pathway genes vis-à-vis podophyllotoxin content in Podophyllum hexandrum Royle. Protoplasma, 2015, 252(5), 1253-1262.
[http://dx.doi.org/10.1007/s00709-015-0757-x] [PMID: 25586110]
[86]
Lau, W.; Sattely, E.S. Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone. Science, 2015, 349(6253), 1224-1228.
[http://dx.doi.org/10.1126/science.aac7202] [PMID: 26359402]
[87]
Farkya, S.; Bisaria, V.S.; Srivastava, A.K. Biotechnological aspects of the production of the anticancer drug podophyllotoxin. Appl. Microbiol. Biotechnol., 2004, 65(5), 504-519.
[http://dx.doi.org/10.1007/s00253-004-1680-9] [PMID: 15378293]
[88]
Ionkova, I. Anticancer compounds from in vitro cultures of rare medicinal plants. Pharmacol. Rev., 2008, 2, 206-218.
[89]
Tang, Y.J.; Li, Y.; Zhong, J.J. Novel biotransformation process of podophyllotoxin to produce podophyllic acid and picropodophyllotoxin by Pseudomonas aeruginosa CCTCC AB93066. Part I: process development. Bioprocess Biosyst. Eng., 2009, 32(5), 663-671.
[http://dx.doi.org/10.1007/s00449-008-0290-9] [PMID: 19115065]
[91]
Puri, S.C.; Nazir, A.; Chawla, R.; Arora, R.; Riyaz-Ul-Hasan, S.; Amna, T.; Ahmed, B.; Verma, V.; Singh, S.; Sagar, R.; Sharma, A.; Kumar, R.; Sharma, R.K.; Qazi, G.N. The endophytic fungus Trametes hirsuta as a novel alternative source of podophyllotoxin and related aryl tetralin lignans. J. Biotechnol., 2006, 122(4), 494-510.
[http://dx.doi.org/10.1016/j.jbiotec.2005.10.015] [PMID: 16375985]
[92]
Kour, A.; Shawl, A.S.; Rehman, S.; Sultan, P.; Qazi, P.H.; Suden, P.; Khajuria, R.; Verma, V. Isolation and identification of an endophytic strain of Fusarium oxysporum producing podophyllotoxin from Juniperus recurva. World J. Microbiol. Biotechnol., 2008, 24(7), 1115-1121.
[http://dx.doi.org/10.1007/s11274-007-9582-5]
[93]
Hsiang, Y.H.; Hertzberg, R.; Hecht, S.; Liu, L.F. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J. Biol. Chem., 1985, 260(27), 14873-14878.
[PMID: 2997227]
[94]
Wall, M.E.; Wani, M.C.; Cook, C.E.; Palmer, K.H.; McPhail, A.T.; Sim, G.A. Plant antitumor Agents. I. The Isolation and Structure of Camptothecin, a Novel Alkaloidal Leukemia and Tumor Inhibitor from Camptotheca acuminate 1, 2. J. Am. Chem. Soc., 1966, 88(16), 3888-3890.
[http://dx.doi.org/10.1021/ja00968a057]
[95]
Shweta, S.; Zuehlke, S.; Ramesha, B.T.; Priti, V.; Mohana Kumar, P.; Ravikanth, G.; Spiteller, M.; Vasudeva, R.; Uma Shaanker, R. Endophytic fungal strains of Fusarium solani, from Apodytes dimidiata E. Mey. ex Arn (Icacinaceae) produce camptothecin, 10-hydroxycamptothecin and 9-methoxycamptothecin. Phytochemistry, 2010, 71(1), 117-122.
[http://dx.doi.org/10.1016/j.phytochem.2009.09.030] [PMID: 19863979]
[96]
Kusari, S.; Zühlke, S.; Spiteller, M. An endophytic fungus from Camptotheca acuminata that produces camptothecin and analogues. J. Nat. Prod., 2009, 72(1), 2-7.
[http://dx.doi.org/10.1021/np800455b] [PMID: 19119919]
[97]
Rehman, S.; Shawl, A.S.; Verma, V.; Kour, A.; Athar, M.; Andrabi, R.; Sultan, P.; Qazi, G.N. An endophytic Neurospora sp. from Nothapodytes foetida producing camptothecin. Prikl. Biokhim. Mikrobiol., 2008, 44(2), 225-231.
[PMID: 18669267]
[98]
Puri, S.C.; Verma, V.; Amna, T.; Qazi, G.N.; Spiteller, M. An endophytic fungus from Nothapodytes foetida that produces camptothecin. J. Nat. Prod., 2005, 68(12), 1717-1719.
[http://dx.doi.org/10.1021/np0502802] [PMID: 16378360]
[99]
Pu, X.; Qu, X.; Chen, F.; Bao, J.; Zhang, G.; Luo, Y. Camptothecin-producing endophytic fungus Trichoderma atroviride LY357: isolation, identification, and fermentation conditions optimization for camptothecin production. Appl. Microbiol. Biotechnol., 2013, 97(21), 9365-9375.
[http://dx.doi.org/10.1007/s00253-013-5163-8] [PMID: 23949997]
[100]
Greeson, J.M.; Sanford, B.; Monti, D.A. St. John’s wort (Hypericum perforatum): a review of the current pharmacological, toxicological, and clinical literature. Psychopharmacology (Berl.), 2001, 153(4), 402-414.
[http://dx.doi.org/10.1007/s002130000625] [PMID: 11243487]
[101]
Barnes, J.; Anderson, L.A.; Phillipson, J.D. St John’s wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties. J. Pharm. Pharmacol., 2001, 53(5), 583-600.
[http://dx.doi.org/10.1211/0022357011775910] [PMID: 11370698]
[102]
Kusari, S.; Lamshöft, M.; Zühlke, S.; Spiteller, M. An endophytic fungus from Hypericum perforatum that produces hypericin. J. Nat. Prod., 2008, 71(2), 159-162.
[http://dx.doi.org/10.1021/np070669k] [PMID: 18220354]
[103]
Yan, L.; Zhao, H.; Zhao, X.; Xu, X.; Di, Y.; Jiang, C.; Shi, J.; Shao, D.; Huang, Q.; Yang, H.; Jin, M. Production of bioproducts by endophytic fungi: chemical ecology, biotechnological applications, bottlenecks, and solutions. Appl. Microbiol. Biotechnol., 2018, 102(15), 6279-6298.
[http://dx.doi.org/10.1007/s00253-018-9101-7] [PMID: 29808328]
[104]
Ahamed, A.; Ahring, B.K. Production of hydrocarbon compounds by endophytic fungi Gliocladium species grown on cellulose. Bioresour. Technol., 2011, 102(20), 9718-9722.
[http://dx.doi.org/10.1016/j.biortech.2011.07.073] [PMID: 21852119]
[105]
El-Gendy, M.M.A.A.; Al-Zahrani, H.A.A.; El-Bondkly, A.M.A. Genome shuffling of Mangrove endophytic Aspergillus luchuensis MERV10 for improving the cholesterol-lowering agent lovastatin under solid state fermentation. Mycobiology, 2016, 44(3), 171-179.
[http://dx.doi.org/10.5941/MYCO.2016.44.3.171] [PMID: 27790068]
[106]
Venugopalan, A.; Srivastava, S. Endophytes as in vitro production platforms of high value plant secondary metabolites. Biotechnol. Adv., 2015, 33(6 Pt 1), 873-887.
[http://dx.doi.org/10.1016/j.biotechadv.2015.07.004] [PMID: 26225453]
[107]
Zhou, X.; Zhu, H.; Liu, L.; Lin, J.; Tang, K. A review: recent advances and future prospects of taxol-producing endophytic fungi. Appl. Microbiol. Biotechnol., 2010, 86(6), 1707-1717.
[http://dx.doi.org/10.1007/s00253-010-2546-y] [PMID: 20358192]
[108]
Zhou, X.; Wei, Y.M.; Zhu, H.F.; Wang, Z.N.; Lin, J.; Liu, L.; Tang, K.X. Protoplast formation, regeneration and transformation from the taxol-producing fungus Ozonium sp. Afr. J. Biotechnol., 2008, 7, 2017-2024.
[http://dx.doi.org/10.5897/AJB2008.000-5050]
[109]
Zhao, K.; Sun, L.; Wang, X.; Li, X.; Wang, X.; Zhou, D. [Screening of high taxol producing fungi by mutagenesis and construction of subtracted cDNA library by suppression subtracted hybridization for differentially expressed genes]. Wei Sheng Wu Xue Bao, 2011, 51(7), 923-933.
[PMID: 22043793]
[110]
Wang, M.; Zhang, W.; Xu, W.; Shen, Y.; Du, L. Optimization of genome shuffling for high-yield production of the antitumor deacetylmycoepoxydiene in an endophytic fungus of mangrove plants. Appl. Microbiol. Biotechnol., 2016, 100(17), 7491-7498.
[http://dx.doi.org/10.1007/s00253-016-7457-0] [PMID: 27067587]
[111]
Wei, Y. Engineering taxol biosynthetic pathway for improving taxol yield in taxol-producing endophytic fungus EFY-21 (Ozonium sp.). Afr. J. Biotechnol., 2012, 11(37), 9094-9101.
[112]
Bian, G.; Yuan, Y.; Tao, H.; Shi, X.; Zhong, X.; Han, Y.; Fu, S.; Fang, C.; Deng, Z.; Liu, T. Production of taxadiene by engineering of mevalonate pathway in Escherichia coli and endophytic fungus Alternaria alternata TPF6. Biotechnol. J., 2017, 12(4)1600697
[http://dx.doi.org/10.1002/biot.201600697] [PMID: 28217906]
[113]
Jahn, L.; Schafhauser, T.; Wibberg, D.; Rückert, C.; Winkler, A.; Kulik, A.; Weber, T.; Flor, L.; van Pée, K.H.; Kalinowski, J.; Ludwig-Müller, J.; Wohlleben, W. Linking secondary metabolites to biosynthesis genes in the fungal endophyte Cyanodermella asteris: The anti-cancer bisanthraquinone skyrin. J. Biotechnol., 2017, 257(257), 233-239.
[http://dx.doi.org/10.1016/j.jbiotec.2017.06.410] [PMID: 28647529]
[114]
El-Moslamy, S.H.; Elkady, M.F.; Rezk, A.H.; Abdel-Fattah, Y.R. Applying Taguchi design and large-scale strategy for mycosynthesis of nano-silver from endophytic Trichoderma harzianum SYA.F4 and its application against phytopathogens. Sci. Rep., 2017, 7, 45297.
[http://dx.doi.org/10.1038/srep45297] [PMID: 28349997]
[115]
Luo, H.; Xu, D.; Xie, R.; Zhang, X.; Wang, J.; Dong, X.; Lai, D.; Zhou, L.; Liu, Y. Research article enhancement of botrallin and TMC-264 production in liquid culture of endophytic fungus Hyalodendriella sp. Ponipodef12 after treatments with metal ions. Electron. J. Biotechnol., 2016, 24, 12-20.
[http://dx.doi.org/10.1016/j.ejbt.2016.09.002]
[116]
Gracida-Rodríguez, J.; Gómez-Valadez, A.; Tovar-Jiménez, X.; Amaro-Reyes, A.; Arana-Cuenca, A.; Zamudio-Pérez, E. Optimization of the biosynthesis of naphthoquinones by endophytic fungi isolated of Ferocactus latispinus. Biologia, 2017, 72(12), 1416-1421.
[http://dx.doi.org/10.1515/biolog-2017-0177]
[117]
Hewage, R.T.; Aree, T.; Mahidol, C.; Ruchirawat, S.; Kittakoop, P. One strain-many compounds (OSMAC) method for production of polyketides, azaphilones, and an isochromanone using the endophytic fungus Dothideomycete sp. Phytochemistry, 2014, 108, 87-94.
[http://dx.doi.org/10.1016/j.phytochem.2014.09.013] [PMID: 25310919]
[118]
Soliman, S.S.M.; Raizada, M.N. Darkness: a crucial factor in fungal taxol production. Front. Microbiol., 2018, 9, 353.
[http://dx.doi.org/10.3389/fmicb.2018.00353] [PMID: 29552002]
[119]
Venugopalan, A.; Srivastava, S. Enhanced camptothecin production by ethanol addition in the suspension culture of the endophyte, Fusarium solani. Bioresour. Technol., 2015, 188(z2), 251-257.
[http://dx.doi.org/10.1016/j.biortech.2014.12.106] [PMID: 25603728]
[120]
Vasanthakumari, M.M.; Jadhav, S.S.; Sachin, N.; Vinod, G.; Shweta, S.; Manjunatha, B.L.; Kumara, P.M.; Ravikanth, G.; Nataraja, K.N.; Uma Shaanker, R. Restoration of camptothecine production in attenuated endophytic fungus on re-inoculation into host plant and treatment with DNA methyltransferase inhibitor. World J. Microbiol. Biotechnol., 2015, 31(10), 1629-1639.
[http://dx.doi.org/10.1007/s11274-015-1916-0] [PMID: 26289161]
[121]
Soliman, S.S.M.; Mosa, K.A.; El-Keblawy, A.A.; Husseiny, M.I. Exogenous and endogenous increase in fungal GGPP increased fungal Taxol production. Appl. Microbiol. Biotechnol., 2017, 101(20), 7523-7533.
[http://dx.doi.org/10.1007/s00253-017-8509-9] [PMID: 28918530]
[122]
Xu, Y.M.; Mafezoli, J.; Oliveira, M.C.; U’Ren, J.M.; Arnold, A.E.; Gunatilaka, A.A. U’Ren, J.M.; Arnold, A.E.; Gunatilaka, A.A. Anteaglonialides A-F and Palmarumycins CE(1)-CE(3) from Anteaglonium sp. FL0768, a fungal endophyte of the spikemoss Selaginella arenicola. J. Nat. Prod., 2015, 78(11), 2738-2747.
[http://dx.doi.org/10.1021/acs.jnatprod.5b00717] [PMID: 26539727]
[123]
Mafezoli, J.; Xu, Y.M.; Hilário, F.; Freidhof, B.; Espinosa-Artiles, P.; Dos Santos, L.C.; de Oliveira, M.C.F.; Gunatilaka, A.A.L. Modulation of polyketide biosynthetic pathway of the endophytic fungus, Anteaglonium sp. FL0768, by copper (II) and anacardic acid. Phytochem. Lett., 2018, 28, 157-163.
[http://dx.doi.org/10.1016/j.phytol.2018.10.011] [PMID: 31354886]
[124]
Sharma, V.; Singamaneni, V.; Sharma, N.; Kumar, A.; Arora, D.; Kushwaha, M.; Bhushan, S.; Jaglan, S.; Gupta, P. Valproic acid induces three novel cytotoxic secondary metabolites in Diaporthe sp., an endophytic fungus from Datura inoxia Mill. Bioorg. Med. Chem. Lett., 2018, 28(12), 2217-2221.
[http://dx.doi.org/10.1016/j.bmcl.2018.04.018] [PMID: 29759727]
[125]
Bertrand, S.; Bohni, N.; Schnee, S.; Schumpp, O.; Gindro, K.; Wolfender, J.L. Metabolite induction via microorganism co-culture: a potential way to enhance chemical diversity for drug discovery. Biotechnol. Adv., 2014, 32(6), 1180-1204.
[http://dx.doi.org/10.1016/j.biotechadv.2014.03.001] [PMID: 24651031]
[126]
Bhalkar, B.N.; Patil, S.M.; Govindwar, S.P. Camptothecine production by mixed fermentation of two endophytic fungi from Nothapodytes nimmoniana. Fungal Biol., 2016, 120(6-7), 873-883.
[http://dx.doi.org/10.1016/j.funbio.2016.04.003] [PMID: 27268247]
[127]
Soliman, S.S.M.; Raizada, M.N. Interactions between co-habitating fungi elicit synthesis of taxol from an endophytic fungus in host Taxus plants. Front. Microbiol., 2013, 4(1), 3.
[http://dx.doi.org/10.3389/fmicb.2013.00003] [PMID: 23346084]

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      • 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=99238
      720μsalphaeurekaselec_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` = 25 limit 1
      840μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 25
      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=25) and sj.journal_id!=25 group by `j`.`nid`) as `aggregate_table`
      1.47msalphaeurekaselec_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=25) and sj.journal_id!=25 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.23msalphaeurekaselec_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=25) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      3.66msalphaeurekaselec_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=25) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      3.16msalphaeurekaselec_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` = '99238'
      420μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 99238
      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` = '99238'
      1.56msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 99238
      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` = '99238' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      930μsalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 99238
      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
      250μsalphaeurekaselec_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
      520μsalphaeurekaselec_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 = 25 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      32.38msalphaeurekaselec_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 = 25 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      42.68msalphaeurekaselec_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 = 25 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      41.5msalphaeurekaselec_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` = 99238 limit 1
      270μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 99238
      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 = 99238 and content_type = 'article' order by status desc limit 1
      530μsalphaeurekaselec_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!=99238 and cd.content_type = 'article' order by rand() limit 20
      54.11msalphaeurekaselec_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` = 173021 limit 1
      250μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 173021
      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
      230μsalphaeurekaselec_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` = 'CMC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      350μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CMC
      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 = '99238' 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) )
      330μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '9808' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      260μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '2698' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      250μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309725698 and j.to_ip >=309725698 )) and ((j.from_date <= 1739847359 and j.to_date >= 1739847359 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2698) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309725698 and j.to_ip >=309725698 )) and ((j.from_date <= 1739847359 and j.to_date >= 1739847359 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2698) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309725698 and j.to_ip >=309725698 )) and ((j.from_date <= 1739847359 and j.to_date >= 1739847359 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2698)
      5.63msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309725698 and j.to_ip >=309725698 )) and ((j.from_date <= 1739847359 and j.to_date >= 1739847359 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9808) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309725698 and j.to_ip >=309725698 )) and ((j.from_date <= 1739847359 and j.to_date >= 1739847359 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9808) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309725698 and j.to_ip >=309725698 )) and ((j.from_date <= 1739847359 and j.to_date >= 1739847359 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9808)
      650μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309725698 and j.to_ip >=309725698 )) and ((j.from_date <= 1739847359 and j.to_date >= 1739847359 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 99238) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309725698 and j.to_ip >=309725698 )) and ((j.from_date <= 1739847359 and j.to_date >= 1739847359 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 99238) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 309725698 and j.to_ip >=309725698 )) and ((j.from_date <= 1739847359 and j.to_date >= 1739847359 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 99238)
      620μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '1855' and is_uploaded = 1 and issue_id = 9808 order by cast(first_page as SIGNED) desc limit 1
      590μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 1855
      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` > '1873' and is_uploaded = 1 and issue_id = 9808 order by cast(first_page as SIGNED) asc limit 1
      450μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 1873
      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` = 'cn'
      190μsalphaeurekaselec_live_10_06_2022ArticleController.php#2486
      Bindings
      • 0: cn
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2486
      • 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` = 2
      230μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 2
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2487
      • 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 `multilanguage_article` where (`language_id` = 2 and `article_id` = 99238)
      5.85msalphaeurekaselec_live_10_06_2022ArticleController.php#2488
      Bindings
      • 0: 2
      • 1: 99238
      Backtrace
      • 15. app/Http/Controllers/ArticleController.php:2488
      • 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
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `keyword` from `multilanguage_keywords` where (`language_id` = 2 and `article_id` = 99238)
      2.73msalphaeurekaselec_live_10_06_2022ArticleController.php#2489
      Bindings
      • 0: 2
      • 1: 99238
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2489
      • 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 CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT_WS(' ',au.last_name, ', ', ifnull(au.initials,''), ' ', au.first_name) as authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs , `au`.*, (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 `multilanguage_authors` as `au` left join `multilanguage_author_affiliation` as `af` on `au`.`id` = `af`.`author_id` where `au`.`article_id` = 99238 group by `au`.`id` order by `au`.`article_id` asc, `au`.`sequence` asc
      3.92msalphaeurekaselec_live_10_06_2022MultiLangAuthor.php#30
      Bindings
      • 0: 99238
      Backtrace
      • 13. app/Models/MultiLangAuthor.php:30
      • 14. app/Http/Controllers/ArticleController.php:2493
      • 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 `multilanguage_journal`.`title` from `multilanguage_journal` where `multilanguage_journal`.`journal_id` = 25 and `language_id` = 2
      340μsalphaeurekaselec_live_10_06_2022ArticleController.php#2495
      Bindings
      • 0: 25
      • 1: 2
      Backtrace
      • 13. app/Http/Controllers/ArticleController.php:2495
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `id` from `multilanguage_article` where `article_id` = 99238 limit 1
      1.83msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 99238
      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` = 25 and `b`.`banner_from_date` <= 1739847359 and `b`.`banner_to_date` >= 1739847359 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: 25
      • 3: 1739847359
      • 4: 1739847359
      • 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` = 25 and `b`.`banner_from_date` <= 1739847359 and `b`.`banner_to_date` >= 1739847359 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.09msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 25
      • 3: 1739847359
      • 4: 1739847359
      • 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='d7b6945f9a2748f74e50be931cc5142e'
      210μsalphaeurekaselec_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\MultiLangArticle
    2MultiLangArticle.php#?
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        o6UriagXQitYUgyDkrbtgoU4M0p2MsdhXO0dPztk
        uc_cart_id
        d7b6945f9a2748f74e50be931cc5142e
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/99238/cn" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/99238/cn
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
        response_headers
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        session_attributes
        0 of 0
        array:5 [ "_token" => "o6UriagXQitYUgyDkrbtgoU4M0p2MsdhXO0dPztk" "uc_cart_id" => "d7b6945f9a2748f74e50be931cc5142e" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/99238/cn" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-18 02:55:59GET/article/99238/cn314413