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Current Chinese Science

Editor-in-Chief

ISSN (Print): 2210-2981
ISSN (Online): 2210-2914

Research Article Section: Pharmacology

Exploring the Molecular Mechanisms of Acorus tatarinowii and Ginseng in the Treatment of Autism Spectrum Disorder Based on Network Pharmacology and Molecular Docking

Author(s): Weijun Chen, Yan Wu, Yuan Hu, Liuyan Zhu, Lingling Wu, Guannan Bai* and Chaochun Zou*

Volume 4, Issue 2, 2024

Published on: 05 January, 2024

Page: [145 - 157] Pages: 13

DOI: 10.2174/0122102981280184231214092958

Price: $65

Abstract

Background: Acorus tatarinowii and Ginseng (AT-G) are traditional Chinese herbal medicines extensively utilized in neurological disorders treatment. However, due to the complex components of AT-G and the pathological mechanism of ASD, the mechanisms involved in the treatment of ASD with AT-G remain elusive.

Objectives: We explored AT-G potential mechanisms in ASD treatment.

Methods: We used the network pharmacology approach to evaluate the beneficial effects of AT-G for ASD, including obtaining the active components of AT-G by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform, detecting the potential targets genes associated with ASD of Genecards and DisGenet databases, network analysis, and virtual docking.

Results: A total of 26 AT-G components, 130 AT-G targets, and 806 ASD-related genes were identified using the bioinformatics analysis tool, including TCMSP, Genecards, and DisGenet. In the intersection of potential pharmacodynamic targets of AT-G and genes associated with ASD, we identified 41 potential common targets. Then, GO enrichment analysis revealed that the common targets were mainly associated with biological processes (i.e., positive regulation of nitric oxide biosynthetic process, response to xenobiotic stimulus), cellular components (i.e., the presynaptic membrane and postsynaptic membrane), and molecular functions (i.e., RNA polymerase II transcription factor activity, identical protein binding). KEGG pathway analysis found that the common targets were enriched in chemical carcinogenesis - receptor activation, fluid shear stress and atherosclerosis, lipid and atherosclerosis, and IL-17 signaling pathways. In addition, 10 core targets were screened from the PPI network (e.g., TNF, AKT1, PTGS2, IL1B, MMP9, PPARG, IFNG, NOS2, TGFB1, and CASP1). Molecular docking revealed that the common component kaempferol has a high affinity for the four primary disease targets.

Conclusion: Our results facilitated the in-depth development of AT-G and their individual components and provided a reference for clinical practice.

Graphical Abstract

[1]
Lord, C.; Elsabbagh, M.; Baird, G.; Veenstra-Vanderweele, J. Autism spectrum disorder. Lancet, 2018, 392(10146), 508-520.
[http://dx.doi.org/10.1016/S0140-6736(18)31129-2] [PMID: 30078460]
[2]
Zhou, H.; Xu, X.; Yan, W.; Zou, X.; Wu, L.; Luo, X.; Li, T.; Huang, Y.; Guan, H.; Chen, X.; Mao, M.; Xia, K.; Zhang, L.; Li, E.; Ge, X.; Zhang, L.; Li, C.; Zhang, X.; Zhou, Y.; Ding, D.; Shih, A.; Fombonne, E.; Zheng, Y.; Han, J.; Sun, Z.; Jiang, Y.; Wang, Y. Prevalence of Autism Spectrum Disorder in China: A nationwide multi-center population-based study among children aged 6 to 12 years. Neurosci. Bull., 2020, 36(9), 961-971.
[http://dx.doi.org/10.1007/s12264-020-00530-6] [PMID: 32607739]
[3]
Lavelle, T.A.; Weinstein, M.C.; Newhouse, J.P.; Munir, K.; Kuhlthau, K.A.; Prosser, L.A. Economic burden of childhood autism spectrum disorders. Pediatrics, 2014, 133(3), e520-e529.
[http://dx.doi.org/10.1542/peds.2013-0763] [PMID: 24515505]
[4]
Dong, Y.; Zhao, K.; Qin, X.; Du, G.; Gao, L. The mechanisms of perineuronal net abnormalities in contributing aging and neurological diseases. Ageing Res. Rev., 2023, 92, 102092.
[http://dx.doi.org/10.1016/j.arr.2023.102092] [PMID: 37839757]
[5]
Gong, L.; Yin, J.; Zhang, Y.; Huang, R.; Lou, Y.; Jiang, H.; Sun, L.; Jia, J.; Zeng, X. Neuroprotective Mechanisms of ginsenoside Rb1 in central nervous system diseases. Front. Pharmacol., 2022, 13, 914352.
[http://dx.doi.org/10.3389/fphar.2022.914352] [PMID: 35721176]
[6]
Zhang, Y.; Long, Y.; Yu, S.; Li, D.; Yang, M.; Guan, Y.; Zhang, D.; Wan, J.; Liu, S.; Shi, A.; Li, N.; Peng, W. Natural volatile oils derived from herbal medicines: A promising therapy way for treating depressive disorder. Pharmacol. Res., 2021, 164, 105376.
[http://dx.doi.org/10.1016/j.phrs.2020.105376] [PMID: 33316383]
[7]
Zhang, F.H.; Wang, Z.M.; Liu, Y.T.; Huang, J.S.; Liang, S.; Wu, H.H.; Xu, Y.T. Bioactivities of serotonin transporter mediate antidepressant effects of Acorus tatarinowii Schott. J. Ethnopharmacol., 2019, 241, 111967.
[http://dx.doi.org/10.1016/j.jep.2019.111967] [PMID: 31128148]
[8]
Zhong, J.; Qiu, X.; Yu, Q.; Chen, H.; Yan, C. A novel polysaccharide from Acorus tatarinowii protects against LPS-induced neuroinflammation and neurotoxicity by inhibiting TLR4-mediated MyD88/NF-κB and PI3K/Akt signaling pathways. Int. J. Biol. Macromol., 2020, 163, 464-475.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.06.266] [PMID: 32621930]
[9]
Hou, W.; Wang, Y.; Zheng, P.; Cui, R. Effects of Ginseng on neurological disorders. Front. Cell. Neurosci., 2020, 14, 55.
[http://dx.doi.org/10.3389/fncel.2020.00055] [PMID: 32265659]
[10]
Wang, N.; Wang, X.; He, M.; Zheng, W.; Qi, D.; Zhang, Y.; Han, C. Ginseng polysaccharides: A potential neuroprotective agent. J. Ginseng Res., 2021, 45(2), 211-217.
[http://dx.doi.org/10.1016/j.jgr.2020.09.002] [PMID: 33841001]
[11]
Zhu, Y.; Wang, Z.; Yu, S.; Zhao, C.; Xu, B.; Liu, R.; Xu, L.; Guo, Y. Neuroprotective Effect of Ginseng fibrous root enzymatic hydrolysate against oxidative stress. Molecules, 2022, 27(22), 7824.
[http://dx.doi.org/10.3390/molecules27227824] [PMID: 36431931]
[12]
Zarneshan, S.N.; Fakhri, S.; Khan, H. Targeting Akt/CREB/BDNF signaling pathway by ginsenosides in neurodegenerative diseases: A mechanistic approach. Pharmacol. Res., 2022, 177, 106099.
[http://dx.doi.org/10.1016/j.phrs.2022.106099] [PMID: 35092819]
[13]
Ji, Y.J.; Kim, H.D.; Lee, E.S.; Jang, G.Y.; Seong, H.A. Heat treatment enhances the neuroprotective effects of crude ginseng saponin by increasing minor ginsenosides. Int. J. Mol. Sci., 2023, 24(8), 7223.
[http://dx.doi.org/10.3390/ijms24087223] [PMID: 37108384]
[14]
Yang, Z.; Zhang, Q.; Yu, L.; Zhu, J.; Cao, Y.; Gao, X. The signaling pathways and targets of traditional Chinese medicine and natural medicine in triple-negative breast cancer. J. Ethnopharmacol., 2021, 264, 113249.
[http://dx.doi.org/10.1016/j.jep.2020.113249] [PMID: 32810619]
[15]
Ding, M.R.; Qu, Y.J.; Hu, B.; An, H.M. Signal pathways in the treatment of Alzheimer’s disease with traditional Chinese medicine. Biomed. Pharmacother., 2022, 152, 113208.
[16]
Zhang, R.; Zhu, X.; Bai, H.; Ning, K. Network pharmacology databases for traditional chinese medicine: Review and Assessment. Front. Pharmacol., 2019, 10, 123.
[http://dx.doi.org/10.3389/fphar.2019.00123] [PMID: 30846939]
[17]
Hopkins, A.L. Network pharmacology: The next paradigm in drug discovery. Nat. Chem. Biol., 2008, 4(11), 682-690.
[http://dx.doi.org/10.1038/nchembio.118] [PMID: 18936753]
[18]
Ru, J.; Li, P.; Wang, J.; Zhou, W.; Li, B.; Huang, C.; Li, P.; Guo, Z.; Tao, W.; Yang, Y.; Xu, X.; Li, Y.; Wang, Y.; Yang, L. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform., 2014, 6(1), 13.
[http://dx.doi.org/10.1186/1758-2946-6-13] [PMID: 24735618]
[19]
Stelzer, G; Rosen, N; Plaschkes, I; Zimmerman, S; Twik, M; Fishilevich, S The GeneCards suite: From gene data mining to disease genome sequence analyses. Curr Protoc Bioinformatics, 2016, 54, 1 30 31-31 30 33.
[20]
Piñero, J.; Saüch, J.; Sanz, F.; Furlong, L.I. The DisGeNET cytoscape app: Exploring and visualizing disease genomics data. Comput. Struct. Biotechnol. J., 2021, 19, 2960-2967.
[http://dx.doi.org/10.1016/j.csbj.2021.05.015] [PMID: 34136095]
[21]
Sherman, B.T.; Hao, M.; Qiu, J.; Jiao, X.; Baseler, M.W.; Lane, H.C.; Imamichi, T.; Chang, W. DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res., 2022, 50(W1), W216-W221.
[http://dx.doi.org/10.1093/nar/gkac194] [PMID: 35325185]
[22]
Szklarczyk, D.; Gable, A.L.; Nastou, K.C.; Lyon, D.; Kirsch, R.; Pyysalo, S.; Doncheva, N.T.; Legeay, M.; Fang, T.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2021: Customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res., 2021, 49(D1), D605-D612.
[http://dx.doi.org/10.1093/nar/gkaa1074] [PMID: 33237311]
[23]
Eberhardt, J.; Santos-Martins, D.; Tillack, A.F.; Forli, S. AutoDock vina 1.2.0: New docking methods, expanded force field, and python bindings. J. Chem. Inf. Model., 2021, 61(8), 3891-3898.
[http://dx.doi.org/10.1021/acs.jcim.1c00203] [PMID: 34278794]
[24]
Hodges, H.; Fealko, C.; Soares, N. Autism spectrum disorder: Definition, epidemiology, causes, and clinical evaluation. Transl. Pediatr., 2020, 9(S1)(Suppl. 1), S55-S65.
[http://dx.doi.org/10.21037/tp.2019.09.09] [PMID: 32206584]
[25]
Kodak, T.; Bergmann, S. Autism spectrum disorder. Pediatr. Clin. North Am., 2020, 67(3), 525-535.
[http://dx.doi.org/10.1016/j.pcl.2020.02.007] [PMID: 32443991]
[26]
Sharma, S.R.; Gonda, X.; Tarazi, F.I. Autism spectrum disorder: Classification, diagnosis and therapy. Pharmacol. Ther., 2018, 190, 91-104.
[http://dx.doi.org/10.1016/j.pharmthera.2018.05.007] [PMID: 29763648]
[27]
Lam, K.Y.C.; Chen, J.; Lam, C.T.W.; Wu, Q.; Yao, P.; Dong, T.T.X.; Lin, H.; Tsim, K.W.K. Asarone from acori tatarinowii rhizoma potentiates the nerve growth factor-induced neuronal differentiation in cultured PC12 cells: A signaling mediated by protein kinase A. PLoS One, 2016, 11(9), e0163337.
[http://dx.doi.org/10.1371/journal.pone.0163337] [PMID: 27685847]
[28]
Mao, J.; Huang, S.; Liu, S.; Feng, X.L.; Yu, M.; Liu, J.; Sun, Y.E.; Chen, G.; Yu, Y.; Zhao, J.; Pei, G. A herbal medicine for Alzheimer’s disease and its active constituents promote neural progenitor proliferation. Aging Cell, 2015, 14(5), 784-796.
[http://dx.doi.org/10.1111/acel.12356] [PMID: 26010330]
[29]
Kim, K.W.; Lee, Y.S.; Choi, B.R.; Yoon, D.; Lee, D.Y. Anti-neuroinflammatory effect of the ethanolic extract of black ginseng through TLR4-MyD88-regulated inhibition of NF-κB and MAPK signaling pathways in LPS-induced BV2 microglial cells. Int. J. Mol. Sci., 2023, 24(20), 15320.
[http://dx.doi.org/10.3390/ijms242015320] [PMID: 37894998]
[30]
Lee, M.J.; Choi, J.H.; Kwon, T.W.; Jo, H.S.; Ha, Y.; Nah, S.Y.; Cho, I.H. Korean Red Ginseng extract ameliorates demyelination by inhibiting infiltration and activation of immune cells in cuprizone-administrated mice. J. Ginseng Res., 2023, 47(5), 672-680.
[http://dx.doi.org/10.1016/j.jgr.2023.05.001] [PMID: 37720568]
[31]
Xu, Z.; Zhou, X.; Hong, X.; Wang, S.; Wei, J.; Huang, J.; Ji, L.; Yang, Y.; Efferth, T.; Hong, C.; Li, C. Essential oil of Acorus tatarinowii Schott inhibits neuroinflammation by suppressing NLRP3 inflammasome activation in 3×Tg-AD transgenic mice. Phytomedicine, 2023, 112, 154695.
[http://dx.doi.org/10.1016/j.phymed.2023.154695] [PMID: 36774844]
[32]
Gao, X.; Li, R.; Luo, L.; Liao, C.; Yang, H.; Mao, S. Alpha-asarone ameliorates neurological dysfunction of subarachnoid hemorrhagic rats in both acute and recovery phases via regulating the CaMKII-dependent pathways. Transl. Stroke Res., 2023, 1-19.
[http://dx.doi.org/10.1007/s12975-023-01139-3] [PMID: 36781743]
[33]
Wang, N.; Wang, H.; Pan, Q.; Kang, J.; Liang, Z.; Zhang, R. The combination of β-asarone and icariin inhibits amyloid-β and reverses cognitive deficits by promoting mitophagy in models of alzheimer’s disease. Oxid. Med. Cell. Longev., 2021, 2021, 1-20.
[http://dx.doi.org/10.1155/2021/7158444] [PMID: 34887998]
[34]
Zhao, X.; Liang, L.; Xu, R.; Cheng, P.; Jia, P.; Bai, Y.; Zhang, Y.; Zhao, X.; Zheng, X.; Xiao, C. Revealing the antiepileptic effect of α-asaronol on pentylenetetrazole-induced seizure rats using NMR-based metabolomics. ACS Omega, 2022, 7(7), 6322-6334.
[http://dx.doi.org/10.1021/acsomega.1c06922] [PMID: 35224394]
[35]
Huang, X.; Li, N.; Pu, Y.; Zhang, T.; Wang, B. Neuroprotective effects of ginseng phytochemicals: Recent perspectives. Molecules, 2019, 24(16), 2939.
[http://dx.doi.org/10.3390/molecules24162939] [PMID: 31416121]
[36]
Wang, W.; Wang, L.; Wang, L.; Li, Y.; Lan, T.; Wang, C.; Chen, X.; Chen, S.; Yu, S. Ginsenoside-Rg1 synergized with voluntary running exercise protects against glial activation and dysregulation of neuronal plasticity in depression. Food Funct., 2023, 14(15), 7222-7239.
[http://dx.doi.org/10.1039/D3FO00496A] [PMID: 37464840]
[37]
Tan, X.; Gu, J.; Zhao, B.; Wang, S.; Yuan, J.; Wang, C.; Chen, J.; Liu, J.; Feng, L.; Jia, X. Ginseng improves cognitive deficit via the RAGE/NF-κB pathway in advanced glycation end product-induced rats. J. Ginseng Res., 2015, 39(2), 116-124.
[http://dx.doi.org/10.1016/j.jgr.2014.09.002] [PMID: 26045684]
[38]
Li, H.; Kang, T.; Qi, B.; Kong, L.; Jiao, Y.; Cao, Y.; Zhang, J.; Yang, J. Neuroprotective effects of ginseng protein on PI3K/Akt signaling pathway in the hippocampus of D -galactose/AlCl3 inducing rats model of Alzheimer’s disease. J. Ethnopharmacol., 2016, 179, 162-169.
[http://dx.doi.org/10.1016/j.jep.2015.12.020] [PMID: 26721223]
[39]
Wu, J.; Yang, Y.; Wan, Y.; Xia, J.; Xu, J.F.; Zhang, L.; Liu, D.; Chen, L.; Tang, F.; Ao, H.; Peng, C. New insights into the role and mechanisms of ginsenoside Rg1 in the management of Alzheimer’s disease. Biomed. Pharmacother., 2022, 152, 113207.
[http://dx.doi.org/10.1016/j.biopha.2022.113207] [PMID: 35667236]
[40]
Oh, J.; Kim, J.S. Compound K derived from ginseng: Neuroprotection and cognitive improvement. Food Funct., 2016, 7(11), 4506-4515.
[http://dx.doi.org/10.1039/C6FO01077F] [PMID: 27801453]
[41]
Gao, X.C.; Zhang, N.X.; Shen, J.M.; Lv, J.W.; Zhang, K.Y.; Sun, Y.; Li, H.; Wang, Y.L.; Cheng, D.D.; Zhao, M.Y.; Zhang, H.; Li, C.N.; Sun, J.M. Screening of the active compounds against neural oxidative damage from ginseng phloem using UPLC-Q-Exactive-MS/MS coupled with the content-effect weighted method. Molecules, 2022, 27(24), 9061.
[http://dx.doi.org/10.3390/molecules27249061] [PMID: 36558193]
[42]
Jakaria, M.; Kim, J.; Karthivashan, G.; Park, S.Y.; Ganesan, P.; Choi, D.K. Emerging signals modulating potential of Ginseng and its active compounds focusing on neurodegenerative diseases. J. Ginseng Res., 2019, 43(2), 163-171.
[http://dx.doi.org/10.1016/j.jgr.2018.01.001] [PMID: 30976157]
[43]
Imran, M.; Salehi, B.; Sharifi-Rad, J.; Aslam Gondal, T.; Saeed, F.; Imran, A.; Shahbaz, M.; Tsouh Fokou, P.V.; Umair Arshad, M.; Khan, H.; Guerreiro, S.G.; Martins, N.; Estevinho, L.M. Kaempferol: A key emphasis to its anticancer potential. Molecules, 2019, 24(12), 2277.
[http://dx.doi.org/10.3390/molecules24122277] [PMID: 31248102]
[44]
Feng, Z.; Wang, C.; Jin, Y.; Meng, Q.; Wu, J.; Sun, H.; Sun, H. Kaempferol-induced GPER upregulation attenuates atherosclerosis via the PI3K/AKT/Nrf2 pathway. Pharm. Biol., 2021, 59(1), 1104-1114.
[http://dx.doi.org/10.1080/13880209.2021.1961823] [PMID: 34403325]
[45]
Dabeek, W.M.; Marra, M.V. Dietary quercetin and kaempferol: Bioavailability and potential cardiovascular-related bioactivity in humans. Nutrients, 2019, 11(10), 2288.
[http://dx.doi.org/10.3390/nu11102288] [PMID: 31557798]
[46]
Chen, Y.; Ma, K.; Si, H.; Duan, Y.; Zhai, H. Network pharmacology integrated molecular docking to reveal the autism and mechanism of baohewan heshiwei wen dan tang. Curr. Pharm. Des., 2022, 28(39), 3231-3241.
[http://dx.doi.org/10.2174/1381612828666220926095922] [PMID: 36165527]
[47]
Chang, S.; Li, X.; Zheng, Y.; Shi, H.; Zhang, D.; Jing, B.; Chen, Z.; Qian, G.; Zhao, G. Kaempferol exerts a neuroprotective effect to reduce neuropathic pain through TLR4/NF‐ĸB signaling pathway. Phytother. Res., 2022, 36(4), 1678-1691.
[http://dx.doi.org/10.1002/ptr.7396] [PMID: 35234314]
[48]
Cheng, K.; Chen, Y.; Yue, C.; Zhang, S.; Pei, Y.P.; Cheng, G.; Liu, D.; Xu, L.; Dong, H.; Zeng, Y. Calsyntenin-1 negatively regulates ICAM5 accumulation in postsynaptic membrane and influences dendritic spine maturation in a mouse model of fragile X syndrome. Front. Neurosci., 2019, 13, 1098.
[http://dx.doi.org/10.3389/fnins.2019.01098] [PMID: 31680833]
[49]
Babatz, T.D.; Kumar, R.A.; Sudi, J.; Dobyns, W.B.; Christian, S.L. Copy number and sequence variants implicate APBA2 as an autism candidate gene. Autism Res., 2009, 2(6), 359-364.
[http://dx.doi.org/10.1002/aur.107] [PMID: 20029827]
[50]
Traglia, M.; Croen, L.A.; Lyall, K.; Windham, G.C.; Kharrazi, M.; DeLorenze, G.N.; Torres, A.R.; Weiss, L.A. Independent maternal and fetal genetic effects on midgestational circulating levels of environmental pollutants. G3, 2017, 7(4), 1287-1299.
[http://dx.doi.org/10.1534/g3.117.039784] [PMID: 28235828]
[51]
Mehta, R.; Kuhad, A.; Bhandari, R. Nitric oxide pathway as a plausible therapeutic target in autism spectrum disorders. Expert Opin. Ther. Targets, 2022, 26(7), 659-679.
[http://dx.doi.org/10.1080/14728222.2022.2100252] [PMID: 35811505]
[52]
Mehta, R.; Bhandari, R.; Kuhad, A. Effects of catechin on a rodent model of autism spectrum disorder: Implications for the role of nitric oxide in neuroinflammatory pathway. Psychopharmacology, 2021, 238(11), 3249-3271.
[http://dx.doi.org/10.1007/s00213-021-05941-5] [PMID: 34448020]
[53]
Santos, J.X.; Rasga, C.; Marques, A.R.; Martiniano, H.; Asif, M.; Vilela, J.; Oliveira, G.; Sousa, L.; Nunes, A.; Vicente, A.M. A role for gene-environment interactions in autism spectrum disorder is supported by variants in genes regulating the effects of exposure to xenobiotics. Front. Neurosci., 2022, 16, 862315.
[http://dx.doi.org/10.3389/fnins.2022.862315] [PMID: 35663546]
[54]
Kong, Y.; Zhou, W.; Sun, Z. Nuclear receptor corepressors in intellectual disability and autism. Mol. Psychiatry, 2020, 25(10), 2220-2236.
[http://dx.doi.org/10.1038/s41380-020-0667-y] [PMID: 32034290]
[55]
Tripathi, M.K.; Kartawy, M.; Ginzburg, S.; Amal, H. Arsenic alters nitric oxide signaling similar to autism spectrum disorder and Alzheimer’s disease-associated mutations. Transl. Psychiatry, 2022, 12(1), 127.
[http://dx.doi.org/10.1038/s41398-022-01890-5] [PMID: 35351881]
[56]
Wang, J.; Fröhlich, H.; Torres, F.B.; Silva, R.L.; Poschet, G.; Agarwal, A.; Rappold, G.A. Mitochondrial dysfunction and oxidative stress contribute to cognitive and motor impairment in FOXP1 syndrome. Proc. Natl. Acad. Sci., 2022, 119(8), e2112852119.
[http://dx.doi.org/10.1073/pnas.2112852119] [PMID: 35165191]
[57]
Singh, K.; Connors, S.L.; Macklin, E.A.; Smith, K.D.; Fahey, J.W.; Talalay, P.; Zimmerman, A.W. Sulforaphane treatment of autism spectrum disorder (ASD). Proc. Natl. Acad. Sci., 2014, 111(43), 15550-15555.
[http://dx.doi.org/10.1073/pnas.1416940111] [PMID: 25313065]
[58]
Thawley, A.J.; Veneziani, L.P.; Rabelo-da-Ponte, F.D.; Riederer, I.; Mendes-da-Cruz, D.A.; Bambini-Junior, V. Aberrant IL-17 levels in rodent models of autism spectrum disorder: A systematic review. Front. Immunol., 2022, 13, 874064.
[http://dx.doi.org/10.3389/fimmu.2022.874064] [PMID: 35757754]
[59]
Nadeem, A.; Ahmad, S.F.; Attia, S.M.; Bakheet, S.A.; Al-Harbi, N.O.; AL-Ayadhi, L.Y. Activation of IL-17 receptor leads to increased oxidative inflammation in peripheral monocytes of autistic children. Brain Behav. Immun., 2018, 67, 335-344.
[http://dx.doi.org/10.1016/j.bbi.2017.09.010] [PMID: 28935156]
[60]
Ahmad, S.F.; Ansari, M.A.; Nadeem, A.; Bakheet, S.A.; Alshammari, M.A.; Attia, S.M. Protection by tyrosine kinase inhibitor, tyrphostin AG126, through the suppression of IL-17A, RORγt, and T-bet signaling, in the BTBR mouse model of autism. Brain Res. Bull., 2018, 142, 328-337.
[http://dx.doi.org/10.1016/j.brainresbull.2018.08.020] [PMID: 30172736]
[61]
Gevezova, M.; Sarafian, V.; Anderson, G.; Maes, M. Inflammation and mitochondrial dysfunction in autism spectrum disorder. CNS Neurol. Disord. Drug Targets, 2020, 19(5), 320-333.
[http://dx.doi.org/10.2174/1871527319666200628015039] [PMID: 32600237]
[62]
Theoharides, T.C.; Tsilioni, I.; Patel, A.B.; Doyle, R. Atopic diseases and inflammation of the brain in the pathogenesis of autism spectrum disorders. Transl. Psychiatry, 2016, 6(6), e844.
[http://dx.doi.org/10.1038/tp.2016.77] [PMID: 27351598]
[63]
Luhach, K.; Kulkarni, G.T.; Singh, V.P.; Sharma, B. Attenuation of neurobehavioural abnormalities by papaverine in prenatal valproic acid rat model of ASD. Eur. J. Pharmacol., 2021, 890, 173663.
[http://dx.doi.org/10.1016/j.ejphar.2020.173663] [PMID: 33127361]
[64]
Zhang, J.; Zhang, J.X.; Zhang, Q.L. PI3K/AKT/mTOR-mediated autophagy in the development of autism spectrum disorder. Brain Res. Bull., 2016, 125, 152-158.
[http://dx.doi.org/10.1016/j.brainresbull.2016.06.007] [PMID: 27320472]
[65]
Thomas, S.D.; Jha, N.K.; Ojha, S.; Sadek, B. mTOR signaling disruption and its association with the development of autism spectrum disorder. Molecules, 2023, 28(4), 1889.
[http://dx.doi.org/10.3390/molecules28041889] [PMID: 36838876]
[66]
Xing, X.; Zhang, J.; Wu, K.; Cao, B.; Li, X.; Jiang, F.; Hu, Z.; Xia, K.; Li, J.D. Suppression of Akt-mTOR pathway rescued the social behavior in Cntnap2-deficient mice. Sci. Rep., 2019, 9(1), 3041.
[http://dx.doi.org/10.1038/s41598-019-39434-5] [PMID: 30816216]
[67]
Li, H.; Zhang, Q.; Wan, R.; Zhou, L.; Xu, X.; Xu, C.; Yu, Y.; Xu, Y.; Xiang, Y.; Tang, S. PLPPR4 haploinsufficiency causes neurodevelopmental disorders by disrupting synaptic plasticity via MTOR signalling. J. Cell. Mol. Med., 2023, 27(21), 3286-3295.
[http://dx.doi.org/10.1111/jcmm.17899] [PMID: 37550884]
[68]
El-Ansary, A.; Alhakbany, M.; Aldbass, A.; Qasem, H.; Al-Mazidi, S.; Bhat, R.S.; Al-Ayadhi, L. Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values. Lipids Health Dis., 2021, 20(1), 155.
[http://dx.doi.org/10.1186/s12944-021-01578-7] [PMID: 34742290]
[69]
Abdallah, M.W.; Pearce, B.D.; Larsen, N.; Greaves-Lord, K.; Nørgaard-Pedersen, B.; Hougaard, D.M.; Mortensen, E.L.; Grove, J. Amniotic fluid MMP-9 and neurotrophins in autism spectrum disorders: An exploratory study. Autism Res., 2012, 5(6), 428-433.
[http://dx.doi.org/10.1002/aur.1254] [PMID: 23008271]
[70]
Pirbhoy, P.S.; Rais, M.; Lovelace, J.W.; Woodard, W.; Razak, K.A.; Binder, D.K.; Ethell, I.M. Acute pharmacological inhibition of matrix metalloproteinase‐9 activity during development restores perineuronal net formation and normalizes auditory processing in Fmr1 KO mice. J. Neurochem., 2020, 155(5), 538-558.
[http://dx.doi.org/10.1111/jnc.15037] [PMID: 32374912]
[71]
Abdallah, M.W.; Mortensen, E.L.; Greaves-Lord, K.; Larsen, N.; Bonefeld-Jørgensen, E.C.; Nørgaard-Pedersen, B.; Hougaard, D.M.; Grove, J. Neonatal levels of neurotrophic factors and risk of autism spectrum disorders. Acta Psychiatr. Scand., 2013, 128(1), 61-69.
[http://dx.doi.org/10.1111/acps.12020] [PMID: 23039165]
[72]
Fallah, H.; Sayad, A.; Ranjbaran, F.; Talebian, F.; Ghafouri-Fard, S.; Taheri, M. IFNG/IFNG-AS1 expression level balance: Implications for autism spectrum disorder. Metab. Brain Dis., 2020, 35(2), 327-333.
[http://dx.doi.org/10.1007/s11011-019-00510-4] [PMID: 31728886]
[73]
Nadeem, A.; Ahmad, S.F.; Attia, S.M.; AL-Ayadhi, L.Y.; Bakheet, S.A.; Al-Harbi, N.O. Oxidative and inflammatory mediators are upregulated in neutrophils of autistic children: Role of IL-17A receptor signaling. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2019, 90, 204-211.
[http://dx.doi.org/10.1016/j.pnpbp.2018.12.002] [PMID: 30529000]
[74]
Liu, L.; Fu, Q.; Ding, H.; Jiang, H.; Zhan, Z.; Lai, Y. Combination of machine learning-based bulk and single-cell genomics reveals necroptosis-related molecular subtypes and immunological features in autism spectrum disorder. Front. Immunol., 2023, 14, 1139420.
[http://dx.doi.org/10.3389/fimmu.2023.1139420] [PMID: 37168851]
[75]
Majerczyk, D.; Ayad, E.G.; Brewton, K.L.; Saing, P.; Hart, P.C. Systemic maternal inflammation promotes ASD via IL-6 and IFN-. Biosci. Rep., 2022, 42(11), BSR20220713.
[http://dx.doi.org/10.1042/BSR20220713] [PMID: 36300375]

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Request history8.2.27PHP Version239msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[23:19:55] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
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  • Application (144ms)time
  • 1 x Application (60.26%)
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    1 x Booting (39.74%)
    94.89ms
    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
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    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
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    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
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    App\Http\Controllers
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    app/Http/Controllers/ArticleController.php:1974-2510
    36 statements were executed, 4 of which were duplicates, 32 unique. Show only duplicated72.56ms
    • 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
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      1.15msalphaeurekaselec_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 ('59689235','/article/137033',1,1739834395,1739834395)
      220μsalphaeurekaselec_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 >= 59689235 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59689235) 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 >= 59689235 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59689235) 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 >= 59689235 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59689235) 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 >= 59689235 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59689235) 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 >= 59689235 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59689235) 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 >= 59689235 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59689235) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 59689235 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59689235) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 59689235 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59689235) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 59689235 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59689235) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 59689235 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59689235) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 59689235 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59689235) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 59689235 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59689235) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 59689235 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59689235) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 59689235 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59689235) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 59689235 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59689235) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 59689235 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59689235) limit 1
      19.05msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 59689235
      • 1: 59689235
      • 2: 59689235
      • 3: 59689235
      • 4: 59689235
      • 5: 59689235
      • 6: 59689235
      • 7: 59689235
      • 8: 59689235
      • 9: 59689235
      • 10: 59689235
      • 11: 59689235
      • 12: 59689235
      • 13: 59689235
      • 14: 59689235
      • 15: 59689235
      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=137033
      970μsalphaeurekaselec_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` = 195 limit 1
      440μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 195
      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=195) and sj.journal_id!=195 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=195) and sj.journal_id!=195 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      590μsalphaeurekaselec_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=195) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      2.25msalphaeurekaselec_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=195) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.9msalphaeurekaselec_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` = '137033'
      190μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 137033
      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` = '137033'
      4.07msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 137033
      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` = '137033' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      810μsalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 137033
      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
      220μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      460μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 195 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      18.08msalphaeurekaselec_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 = 195 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      1.79msalphaeurekaselec_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 = 195 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      1.37msalphaeurekaselec_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` = 137033 limit 1
      160μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 137033
      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 = 137033 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` = 225286 limit 1
      170μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 225286
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      200μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CCS' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      270μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CCS
      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 = '137033' 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) )
      380μsalphaeurekaselec_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 = '13293' 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) )
      280μsalphaeurekaselec_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 = '3542' 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) )
      290μsalphaeurekaselec_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 <= 59689235 and j.to_ip >=59689235 )) and ((j.from_date <= 1739834395 and j.to_date >= 1739834395 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3542) 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 <= 59689235 and j.to_ip >=59689235 )) and ((j.from_date <= 1739834395 and j.to_date >= 1739834395 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3542) 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 <= 59689235 and j.to_ip >=59689235 )) and ((j.from_date <= 1739834395 and j.to_date >= 1739834395 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3542)
      9.21msalphaeurekaselec_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 <= 59689235 and j.to_ip >=59689235 )) and ((j.from_date <= 1739834395 and j.to_date >= 1739834395 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 13293) 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 <= 59689235 and j.to_ip >=59689235 )) and ((j.from_date <= 1739834395 and j.to_date >= 1739834395 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 13293) 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 <= 59689235 and j.to_ip >=59689235 )) and ((j.from_date <= 1739834395 and j.to_date >= 1739834395 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 13293)
      560μsalphaeurekaselec_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 <= 59689235 and j.to_ip >=59689235 )) and ((j.from_date <= 1739834395 and j.to_date >= 1739834395 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 137033) 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 <= 59689235 and j.to_ip >=59689235 )) and ((j.from_date <= 1739834395 and j.to_date >= 1739834395 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 137033) 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 <= 59689235 and j.to_ip >=59689235 )) and ((j.from_date <= 1739834395 and j.to_date >= 1739834395 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 137033)
      520μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '145' and is_uploaded = 1 and issue_id = 13293 order by cast(first_page as SIGNED) desc limit 1
      440μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 145
      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` > '157' and is_uploaded = 1 and issue_id = 13293 order by cast(first_page as SIGNED) asc limit 1
      370μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 157
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      160μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      160μsalphaeurekaselec_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` = 137033 limit 1
      2.4msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 137033
      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` = 195 and `b`.`banner_from_date` <= 1739834395 and `b`.`banner_to_date` >= 1739834395 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: 195
      • 3: 1739834395
      • 4: 1739834395
      • 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` = 195 and `b`.`banner_from_date` <= 1739834395 and `b`.`banner_to_date` >= 1739834395 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: 195
      • 3: 1739834395
      • 4: 1739834395
      • 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='7dad1ed5dee440433de808c0f23a4590'
      250μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        sguijhSu7cZHXtDEti7cnGOhK5p1tkJ2dmxKjcj3
        uc_cart_id
        7dad1ed5dee440433de808c0f23a4590
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/article/137033" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/137033
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