Generic placeholder image

Current Analytical Chemistry

Editor-in-Chief

ISSN (Print): 1573-4110
ISSN (Online): 1875-6727

Review Article

Ultrasmall Nanoclusters: Synthesis and Applications as an Emerging Platform for Imaging and Therapy

Author(s): Xiaohui Zhang, Deborah Sultan, Gyu Seong Heo, Hannah Luehmann, Lisa Detering and Yongjian Liu*

Volume 17, Issue 3, 2021

Published on: 30 December, 2019

Page: [287 - 301] Pages: 15

DOI: 10.2174/1573411016666191230151648

Price: $65

Abstract

Background: Ultrasmall nanoclusters (USNCs) have attracted tremendous attention owing to their unique properties that make them desirable for the development of personalized medicine, such as tunable emission, straightforward modification, and renal clearance. Hence, USNCs have emerged as potential materials for nanotheranostics.

Objective: For decades, great efforts have been devoted to the bio-applications of USNCs, promising platforms to satisfy the increasing demand for precise diagnostic and targeted therapeutics. Herein, we summarize the most recent advances of USNCs in biomedical applications and provide our perspective on the future development of USNCs.

Results: This review briefly summarized the synthetic methods of metallic USNCs and discussed their recent applications for cancer imaging and therapy.

Conclusion: USNCs have shown their potential for accurate diagnosis and specific delivery of therapeutics in preclinical research.

Keywords: Cancer, imaging, therapy, ultrasmall nanocluster, medicine, nanotheranostics.

Graphical Abstract

[1]
Nutzenadel, C.; Zuttell, A.; Chartouni, D.; Schmid, G.; Schlapbach, L. Critical size and surface effect of the hydrogen interaction of palladium clusters. Eur. Phys. J. D, 2000, 8(2), 245-250.
[http://dx.doi.org/10.1007/s100530050033]
[2]
Link, S.; El-Sayed, M.A. Optical properties and ultrafast dynamics of metallic nanocrystals. Annu. Rev. Phys. Chem., 2003, 54, 331-366.
[http://dx.doi.org/10.1146/annurev.physchem.54.011002.103759] [PMID: 12626731]
[3]
Zheng, J.; Nicovich, P.R.; Dickson, R.M. Highly fluorescent noble-metal quantum dots. Annu. Rev. Phys. Chem., 2007, 58, 409-431.
[http://dx.doi.org/10.1146/annurev.physchem.58.032806.104546] [PMID: 17105412]
[4]
Liu, Y.; Welch, M.J. Nanoparticles labeled with positron emitting nuclides: Advantages, methods, and applications. Bioconjug. Chem., 2012, 23(4), 671-682.
[http://dx.doi.org/10.1021/bc200264c] [PMID: 22242601]
[5]
Sun, X.; Cai, W.; Chen, X. Positron emission tomography imaging using radiolabeled inorganic nanomaterials. Acc. Chem. Res., 2015, 48(2), 286-294.
[http://dx.doi.org/10.1021/ar500362y] [PMID: 25635467]
[6]
Sztandera, K.; Gorzkiewicz, M.; Klajnert-Maculewicz, B. Gold nanoparticles in cancer treatment. Mol. Pharm., 2019, 16(1), 1-23.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00810] [PMID: 30452861]
[7]
Zhao, Y.; Sultan, D.; Detering, L.; Luehmann, H.; Liu, Y. Facile synthesis, pharmacokinetic and systemic clearance evaluation, and positron emission tomography cancer imaging of 64Cu-Au alloy nanoclusters. Nanoscale, 2014, 6(22), 13501-13509.
[http://dx.doi.org/10.1039/C4NR04569F] [PMID: 25266128]
[8]
Zhao, Y.; Detering, L.; Sultan, D.; Cooper, M.L.; You, M.; Cho, S.; Meier, S.L.; Luehmann, H.; Sun, G.; Rettig, M.; Dehdashti, F.; Wooley, K.L.; DiPersio, J.F.; Liu, Y. Gold nanoclusters doped with 64Cu for CXCR4 positron emission tomography imaging of breast cancer and metastasis. ACS Nano, 2016, 10(6), 5959-5970.
[http://dx.doi.org/10.1021/acsnano.6b01326] [PMID: 27159079]
[9]
Zhang, X.D.; Luo, Z.; Chen, J.; Song, S.; Yuan, X.; Shen, X.; Wang, H.; Sun, Y.; Gao, K.; Zhang, L.; Fan, S.; Leong, D.T.; Guo, M.; Xie, J. Ultrasmall glutathione-protected gold nanoclusters as next generation radiotherapy sensitizers with high tumor uptake and high renal clearance. Sci. Rep., 2015, 5, 8669.
[http://dx.doi.org/10.1038/srep08669] [PMID: 25727895]
[10]
Jiang, X.; Du, B.; Huang, Y.; Zheng, J. Ultrasmall noble metal nanoparticles: Breakthroughs and biomedical implications. Nano Today, 2018, 21, 106-125.
[http://dx.doi.org/10.1016/j.nantod.2018.06.006] [PMID: 31327979]
[11]
Tan, X.; Jin, R. Ultrasmall metal nanoclusters for bio-related applications. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 2013, 5(6), 569-581.
[http://dx.doi.org/10.1002/wnan.1237] [PMID: 23939885]
[12]
Wang, Q.; Wang, S.; Hu, X.; Li, F.; Ling, D. Controlled synthesis and assembly of ultra-small nanoclusters for biomedical applications. Biomater. Sci., 2019, 7(2), 480-489.
[http://dx.doi.org/10.1039/C8BM01200H] [PMID: 30488906]
[13]
Zarschler, K.; Rocks, L.; Licciardello, N.; Boselli, L.; Polo, E.; Garcia, K.P.; De Cola, L.; Stephan, H.; Dawson, K.A. Ultrasmall inorganic nanoparticles: State-of-the-art and perspectives for biomedical applications. Nanomedicine (Lond.), 2016, 12(6), 1663-1701.
[http://dx.doi.org/10.1016/j.nano.2016.02.019] [PMID: 27013135]
[14]
Chen, F.; Ma, K.; Benezra, M.; Zhang, L.; Cheal, S.M.; Phillips, E.; Yoo, B.; Pauliah, M.; Overholtzer, M.; Zanzonico, P.; Sequeira, S.; Gonen, M.; Quinn, T.; Wiesner, U.; Bradbury, M.S. Cancer-targeting ultrasmall silica nanoparticles for clinical translation: Physicochemical structure and biological property correlations. Chem. Mater., 2017, 29(20), 8766-8779.
[http://dx.doi.org/10.1021/acs.chemmater.7b03033] [PMID: 29129959]
[15]
Mao, F.; Wen, L.; Sun, C.; Zhang, S.; Wang, G.; Zeng, J.; Wang, Y.; Ma, J.; Gao, M.; Li, Z. Ultrasmall biocompatible Bi2Se3 nanodots for multimodal imaging-guided synergistic radiophotothermal therapy against cancer. ACS Nano, 2016, 10(12), 11145-11155.
[http://dx.doi.org/10.1021/acsnano.6b06067] [PMID: 28024338]
[16]
Wen, L.; Chen, L.; Zheng, S.; Zeng, J.; Duan, G.; Wang, Y.; Wang, G.; Chai, Z.; Li, Z.; Gao, M. Ultrasmall biocompatible Wo3-x nanodots for multi-modality imaging and combined therapy of cancers. Adv. Mater., 2016, 28(25), 5072-5079.
[http://dx.doi.org/10.1002/adma.201506428] [PMID: 27136070]
[17]
Dehaini, D.; Fang, R.H.; Luk, B.T.; Pang, Z.; Hu, C.M.; Kroll, A.V.; Yu, C.L.; Gao, W.; Zhang, L. Ultra-small lipid-polymer hybrid nanoparticles for tumor-penetrating drug delivery. Nanoscale, 2016, 8(30), 14411-14419.
[http://dx.doi.org/10.1039/C6NR04091H] [PMID: 27411852]
[18]
Mendes, M.; Miranda, A.; Cova, T.; Gonçalves, L.; Almeida, A.J.; Sousa, J.J.; do Vale, M.L.C.; Marques, E.F.; Pais, A.; Vitorino, C. Modeling of ultra-small lipid nanoparticle surface charge for targeting glioblastoma. Eur. J. Pharm. Sci., 2018, 117, 255-269.
[http://dx.doi.org/10.1016/j.ejps.2018.02.024] [PMID: 29486328]
[19]
Shen, S.; Jiang, D.; Cheng, L.; Chao, Y.; Nie, K.; Dong, Z.; Kutyreff, C.J.; Engle, J.W.; Huang, P.; Cai, W.; Liu, Z. Renal-clearable ultrasmall coordination polymer nanodots for chelator-free 64Cu-labeling and imaging-guided enhanced radiotherapy of cancer. ACS Nano, 2017, 11(9), 9103-9111.
[http://dx.doi.org/10.1021/acsnano.7b03857] [PMID: 28853861]
[20]
Schmid, G. Metal-clusters and cluster metals. Polyhedron, 1988, 7(22-23), 2321-2329.
[http://dx.doi.org/10.1016/S0277-5387(00)86349-4]
[21]
Weare, W.W.; Reed, S.M.; Warner, M.G.; Hutchison, J.E. Improved synthesis of small (dcore ≈ 1.5 nm) phosphine-stabilized gold nanoparticles. J. Am. Chem. Soc., 2000, 122(51), 12890-12891.
[http://dx.doi.org/10.1021/ja002673n]
[22]
Wegner, K.; Piseri, P.; Tafreshi, H.V.; Milani, P. Cluster beam deposition: A tool for nanoscale science and technology. J. Phys. D Appl. Phys., 2006, 39(22), R439-R459.
[http://dx.doi.org/10.1088/0022-3727/39/22/R02]
[23]
Nikitin, A.A.; Shchetinin, I.V.; Tabachkova, N.Y.; Soldatov, M.A.; Soldatov, A.V.; Sviridenkova, N.V.; Beloglazkina, E.K.; Savchenko, A.G.; Fedorova, N.D.; Abakumov, M.A.; Majouga, A.G. Synthesis of iron oxide nanoclusters by thermal decomposition. Langmuir, 2018, 34(15), 4640-4650.
[http://dx.doi.org/10.1021/acs.langmuir.8b00753] [PMID: 29566327]
[24]
Park, J.; An, K.; Hwang, Y.; Park, J.G.; Noh, H.J.; Kim, J.Y.; Park, J.H.; Hwang, N.M.; Hyeon, T. Ultra-large-scale syntheses of monodisperse nanocrystals. Nat. Mater., 2004, 3(12), 891-895.
[http://dx.doi.org/10.1038/nmat1251] [PMID: 15568032]
[25]
Kim, B.H.; Hackett, M.J.; Park, J.; Hyeon, T. Synthesis, characterization, and application of ultrasmall nanoparticles. Chem. Mater., 2014, 26(1), 59-71.
[http://dx.doi.org/10.1021/cm402225z]
[26]
Shang, L.; Dong, S.J.; Nienhaus, G.U. Ultra-small fluorescent metal nanoclusters: Synthesis and biological applications. Nano Today, 2011, 6(4), 401-418.
[http://dx.doi.org/10.1016/j.nantod.2011.06.004]
[27]
Yao, Q.; Yuan, X.; Fung, V.; Yu, Y.; Leong, D.T.; Jiang, D.E.; Xie, J. Understanding seed-mediated growth of gold nanoclusters at molecular level. Nat. Commun., 2017, 8(1), 927.
[http://dx.doi.org/10.1038/s41467-017-00970-1] [PMID: 29030559]
[28]
Zhou, T.; Zhu, J.; Gong, L.; Nong, L.; Liu, J. Amphiphilic block copolymer-guided in situ fabrication of stable and highly controlled luminescent copper nanoassemblies. J. Am. Chem. Soc., 2019, 141(7), 2852-2856.
[http://dx.doi.org/10.1021/jacs.8b12026] [PMID: 30717593]
[29]
Jin, R.; Zeng, C.; Zhou, M.; Chen, Y. Atomically precise colloidal metal nanoclusters and nanoparticles: Fundamentals and opportunities. Chem. Rev., 2016, 116(18), 10346-10413.
[http://dx.doi.org/10.1021/acs.chemrev.5b00703] [PMID: 27585252]
[30]
Yang, Y.; Ghildiyal, P.; Zachariah, M.R. Thermal shock synthesis of metal nanoclusters within on-the-fly graphene particles. Langmuir, 2019, 35(9), 3413-3420.
[http://dx.doi.org/10.1021/acs.langmuir.8b03532] [PMID: 30698983]
[31]
Brust, M.; Walker, M.; Bethell, D.; Schiffrin, D.J.; Whyman, R. Synthesis of thiol-derivatised gold nanoparticles in a two-phase liquid–liquid system. J. Chem. Soc. Chem. Commun., 1994, (7), 801-802.
[http://dx.doi.org/10.1039/C39940000801]
[32]
Turkevich, J.; Stevenson, P.C.; Hillier, J. A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss. Faraday Soc., 1951, 11(0), 55-75.
[http://dx.doi.org/10.1039/df9511100055]
[33]
Frens, G. Controlled nucleation for the regulation of the particle size in monodisperse gold suspensions. Nat. Phys. Sci (Lond.), 1973, 241, 20.
[http://dx.doi.org/10.1038/physci241020a0]
[34]
Poonthiyil, V.; Golovko, V.B.; Fairbanks, A.J. Control of gold nanostructure morphology by variation of temperature and reagent ratios in the Turkevich reaction. Aust. J. Chem., 2015, 68(6), 858-862.
[http://dx.doi.org/10.1071/CH14446]
[35]
Larm, N.E.; Essner, J.B.; Pokpas, K.; Canon, J.A.; Jahed, N.; Iwuoha, E.I.; Baker, G.A. Room-temperature Turkevich method: Formation of gold nanoparticles at the speed of mixing using cyclic oxocarbon reducing agents. J. Phys. Chem. C, 2018, 122(9), 5105-5118.
[http://dx.doi.org/10.1021/acs.jpcc.7b10536]
[36]
Oh, E.; Susumu, K.; Goswami, R.; Mattoussi, H. One-phase synthesis of water-soluble gold nanoparticles with control over size and surface functionalities. Langmuir, 2010, 26(10), 7604-7613.
[http://dx.doi.org/10.1021/la904438s] [PMID: 20121172]
[37]
Song, J.; Kim, D.; Lee, D. Size control in the synthesis of 1-6 nm gold nanoparticles via solvent-controlled nucleation. Langmuir, 2011, 27(22), 13854-13860.
[http://dx.doi.org/10.1021/la203113r] [PMID: 21955125]
[38]
Piella, J.; Bastus, N.G.; Puntes, V. Size-controlled synthesis of sub-10-nanometer citrate-stabilized gold nanoparticles and related optical properties. Chem. Mater., 2016, 28(4), 1066-1075.
[http://dx.doi.org/10.1021/acs.chemmater.5b04406]
[39]
Zhao, Y.; Sultan, D.; Detering, L.; Cho, S.; Sun, G.; Pierce, R.; Wooley, K.L.; Liu, Y. Copper-64-alloyed gold nanoparticles for cancer imaging: Improved radiolabel stability and diagnostic accuracy. Angew. Chem. Int. Ed. Engl., 2014, 53(1), 156-159.
[http://dx.doi.org/10.1002/anie.201308494] [PMID: 24272951]
[40]
Nuzzo, R.G.; Allara, D.L. Absorption of bifunctional organic disulfides on gold surfaces. J. Am. Chem. Soc., 1983, 105(13), 4481-4483.
[http://dx.doi.org/10.1021/ja00351a063]
[41]
Keller, H.; Simak, P.; Schrepp, W.; Dembowski, J. Surface-chemistry of thiols on copper - an efficient way of producing multilayers. Thin Solid Films, 1994, 244(1-2), 799-805.
[http://dx.doi.org/10.1016/0040-6090(94)90574-6]
[42]
Pakiari, A.H.; Jamshidi, Z. Nature and strength of M-S bonds (m = Au, Ag, and Cu) in binary alloy gold clusters. J. Phys. Chem. A, 2010, 114(34), 9212-9221.
[http://dx.doi.org/10.1021/jp100423b] [PMID: 20687518]
[43]
Yuan, X.; Zhang, B.; Luo, Z.; Yao, Q.; Leong, D.T.; Yan, N.; Xie, J. Balancing the rate of cluster growth and etching for gram-scale synthesis of thiolate-protected Au(25) nanoclusters with atomic precision. Angew. Chem. Int. Ed. Engl., 2014, 53(18), 4623-4627.
[http://dx.doi.org/10.1002/anie.201311177] [PMID: 24664874]
[44]
New, S.Y.; Lee, S.T.; Su, X.D. DNA-templated silver nanoclusters: Structural correlation and fluorescence modulation. Nanoscale, 2016, 8(41), 17729-17746.
[http://dx.doi.org/10.1039/C6NR05872H] [PMID: 27722695]
[45]
Tiwari, J.N.; Nath, K.; Kumar, S.; Tiwari, R.N.; Kemp, K.C.; Le, N.H.; Youn, D.H.; Lee, J.S.; Kim, K.S. Stable platinum nanoclusters on genomic DNA-graphene oxide with a high oxygen reduction reaction activity. Nat. Commun., 2013, 4, 2221.
[http://dx.doi.org/10.1038/ncomms3221] [PMID: 23900456]
[46]
Fan, J.A.; He, Y.; Bao, K.; Wu, C.; Bao, J.; Schade, N.B.; Manoharan, V.N.; Shvets, G.; Nordlander, P.; Liu, D.R.; Capasso, F. DNA-enabled self-assembly of plasmonic nanoclusters. Nano Lett., 2011, 11(11), 4859-4864.
[http://dx.doi.org/10.1021/nl203194m] [PMID: 22007607]
[47]
Nandi, I.; Chall, S.; Chowdhury, S.; Mitra, T.; Roy, S.S.; Chattopadhyay, K. Protein fibril-templated biomimetic synthesis of highly fluorescent gold nanoclusters and their applications in cysteine sensing. ACS Omega, 2018, 3(7), 7703-7714.
[http://dx.doi.org/10.1021/acsomega.8b01033] [PMID: 30221238]
[48]
Vinluan, R.D., III; Liu, J.; Zhou, C.; Yu, M.; Yang, S.; Kumar, A.; Sun, S.; Dean, A.; Sun, X.; Zheng, J. Glutathione-coated luminescent gold nanoparticles: A surface ligand for minimizing serum protein adsorption. ACS Appl. Mater. Interfaces, 2014, 6(15), 11829-11833.
[http://dx.doi.org/10.1021/am5031374] [PMID: 25029478]
[49]
Chen, H.; Li, S.; Li, B.; Ren, X.; Li, S.; Mahounga, D.M.; Cui, S.; Gu, Y.; Achilefu, S. Folate-modified gold nanoclusters as near-infrared fluorescent probes for tumor imaging and therapy. Nanoscale, 2012, 4(19), 6050-6064.
[http://dx.doi.org/10.1039/c2nr31616a] [PMID: 22930451]
[50]
Adnan, N.N.M.; Ahmad, S.; Kuchel, R.P.; Boyer, C. Exploring the potential of linear polymer structures for the synthesis of fluorescent gold nanoclusters. Mater. Chem. Front., 2017, 1(1), 80-90.
[http://dx.doi.org/10.1039/C6QM00109B]
[51]
Kambe, T.; Haruta, N.; Imaoka, T.; Yamamoto, K. Solution-phase synthesis of Al13- using a dendrimer template. Nat. Commun., 2017, 8(1), 2046.
[http://dx.doi.org/10.1038/s41467-017-02250-4] [PMID: 29229924]
[52]
Yu, T.; Wang, W.; Chen, J.; Zeng, Y.; Li, Y.; Yang, G.; Li, Y. Dendrimer-encapsulated Pt nanoparticles: an artificial enzyme for hydrogen production. J. Phys. Chem. C, 2012, 116(19), 10516-10521.
[http://dx.doi.org/10.1021/jp3021672]
[53]
Pal, N.K.; Kryschi, C. A facile synthesis of highly stable and luminescent Ag clusters: A steady-state and time-resolved spectroscopy study. Phys. Chem. Chem. Phys., 2015, 17(3), 1957-1965.
[http://dx.doi.org/10.1039/C4CP03683B] [PMID: 25475027]
[54]
Jin, Q.; Zhu, W.; Jiang, D.; Zhang, R.; Kutyreff, C.J.; Engle, J.W.; Huang, P.; Cai, W.; Liu, Z.; Cheng, L. Ultra-small iron-gallic acid coordination polymer nanoparticles for chelator-free labeling of 64Cu and multimodal imaging-guided photothermal therapy. Nanoscale, 2017, 9(34), 12609-12617.
[http://dx.doi.org/10.1039/C7NR03086J] [PMID: 28825066]
[55]
Tang, R.; Xue, J.; Xu, B.; Shen, D.; Sudlow, G.P.; Achilefu, S. Tunable ultrasmall visible-to-extended near-infrared emitting silver sulfide quantum dots for integrin-targeted cancer imaging. ACS Nano, 2015, 9(1), 220-230.
[http://dx.doi.org/10.1021/nn5071183] [PMID: 25560768]
[56]
Chen, Y.; Montana, D.M.; Wei, H.; Cordero, J.M.; Schneider, M.; Le Guével, X.; Chen, O.; Bruns, O.T.; Bawendi, M.G. Shortwave infrared in vivo imaging with gold nanoclusters. Nano Lett., 2017, 17(10), 6330-6334.
[http://dx.doi.org/10.1021/acs.nanolett.7b03070] [PMID: 28952734]
[57]
Kurdekar, A.D.; Avinash Chunduri, L.A.; Manohar, C.S.; Haleyurgirisetty, M.K.; Hewlett, I.K.; Venkataramaniah, K. Streptavidin-conjugated gold nanoclusters as ultrasensitive fluorescent sensors for early diagnosis of HIV infection. Sci. Adv., 2018, 4(11), 6280.
[http://dx.doi.org/10.1126/sciadv.aar6280] [PMID: 30474052]
[58]
Peng, C.; Gao, X.; Xu, J.; Du, B.; Ning, X.; Tang, S.; Bachoo, R.M.; Yu, M.; Ge, W.P.; Zheng, J. Targeting orthotopic gliomas with renal-clearable luminescent gold nanoparticles. Nano Res., 2017, 10(4), 1366-1376.
[http://dx.doi.org/10.1007/s12274-017-1472-z] [PMID: 29034063]
[59]
Ni, D.; Bu, W.; Ehlerding, E.B.; Cai, W.; Shi, J. Engineering of inorganic nanoparticles as magnetic resonance imaging contrast agents. Chem. Soc. Rev., 2017, 46(23), 7438-7468.
[http://dx.doi.org/10.1039/C7CS00316A] [PMID: 29071327]
[60]
El-Boubbou, K. Magnetic iron oxide nanoparticles as drug carriers: Clinical relevance. Nanomedicine (Lond.), 2018, 13(8), 953-971.
[http://dx.doi.org/10.2217/nnm-2017-0336] [PMID: 29376469]
[61]
Min, Y.; Caster, J.M.; Eblan, M.J.; Wang, A.Z. Clinical translation of nanomedicine. Chem. Rev., 2015, 115(19), 11147-11190.
[http://dx.doi.org/10.1021/acs.chemrev.5b00116] [PMID: 26088284]
[62]
Li, Z.; Yi, P.; Sun, Q.; Lei, H.; Zhao, H.; Zhu, Z.; Smith, S.C.; Lan, M.; Lu, G. Ultrasmall water-soluble and biocompatible magnetic iron oxide nanoparticles as positive and negative dual contrast agents. Adv. Funct. Mater., 2012, 22(11), 2387-2393.
[http://dx.doi.org/10.1002/adfm.201103123]
[63]
Lu, Y.; Xu, Y.J.; Zhang, G.B.; Ling, D.; Wang, M.Q.; Zhou, Y.; Wu, Y.D.; Wu, T.; Hackett, M.J.; Hyo Kim, B.; Chang, H.; Kim, J.; Hu, X.T.; Dong, L.; Lee, N.; Li, F.; He, J.C.; Zhang, L.; Wen, H.Q.; Yang, B.; Hong Choi, S.; Hyeon, T.; Zou, D.H. Iron oxide nanoclusters for T1 magnetic resonance imaging of non-human primates. Nat. Biomed. Eng., 2017, 1(8), 637-643.
[http://dx.doi.org/10.1038/s41551-017-0116-7] [PMID: 31015599]
[64]
Wang, L.; Huang, J.; Chen, H.; Wu, H.; Xu, Y.; Li, Y.; Yi, H.; Wang, Y.A.; Yang, L.; Mao, H. Exerting enhanced permeability and retention effect driven delivery by ultrafine iron oxide nanoparticles with T1-T2 switchable magnetic resonance imaging contrast. ACS Nano, 2017, 11(5), 4582-4592.
[http://dx.doi.org/10.1021/acsnano.7b00038] [PMID: 28426929]
[65]
Li, F.; Liang, Z.; Liu, J.; Sun, J.; Hu, X.; Zhao, M.; Liu, J.; Bai, R.; Kim, D.; Sun, X.; Hyeon, T.; Ling, D. Dynamically reversible iron oxide nanoparticle assemblies for targeted amplification of T1-weighted magnetic resonance imaging of tumors. Nano Lett., 2019, 19(7), 4213-4220.
[http://dx.doi.org/10.1021/acs.nanolett.8b04411] [PMID: 30719918]
[66]
Chen, F.; Goel, S.; Hernandez, R.; Graves, S.A.; Shi, S.; Nickles, R.J.; Cai, W. Dynamic positron emission tomography imaging of renal clearable gold nanoparticles. Small, 2016, 12(20), 2775-2782.
[http://dx.doi.org/10.1002/smll.201600194] [PMID: 27062146]
[67]
Zhou, C.; Hao, G.; Thomas, P.; Liu, J.; Yu, M.; Sun, S.; Öz, O.K.; Sun, X.; Zheng, J. Near-infrared emitting radioactive gold nanoparticles with molecular pharmacokinetics. Angew. Chem. Int. Ed. Engl., 2012, 51(40), 10118-10122.
[http://dx.doi.org/10.1002/anie.201203031] [PMID: 22961978]
[68]
Sultan, D.; Ye, D.; Heo, G.S.; Zhang, X.; Luehmann, H.; Yue, Y.; Detering, L.; Komarov, S.; Taylor, S.; Tai, Y.C.; Rubin, J.B.; Chen, H.; Liu, Y. Focused ultrasound enabled trans-blood brain barrier delivery of gold nanoclusters: effect of surface charges and quantification using positron emission tomography. Small, 2018, 14(30)e1703115
[http://dx.doi.org/10.1002/smll.201703115] [PMID: 29966035]
[69]
Ye, D.; Sultan, D.; Zhang, X.; Yue, Y.; Heo, G.S.; Kothapalli, S.V.V.N.; Luehmann, H.; Tai, Y.C.; Rubin, J.B.; Liu, Y.; Chen, H. Focused ultrasound-enabled delivery of radiolabeled nanoclusters to the pons. J. Control. Release, 2018, 283, 143-150.
[http://dx.doi.org/10.1016/j.jconrel.2018.05.039] [PMID: 29864474]
[70]
Ye, D.; Zhang, X.; Yue, Y.; Raliya, R.; Biswas, P.; Taylor, S.; Tai, Y.C.; Rubin, J.B.; Liu, Y.; Chen, H. Focused ultrasound combined with microbubble-mediated intranasal delivery of gold nanoclusters to the brain. J. Control. Release, 2018, 286, 145-153.
[http://dx.doi.org/10.1016/j.jconrel.2018.07.020] [PMID: 30009893]
[71]
Benezra, M.; Penate-Medina, O.; Zanzonico, P.B.; Schaer, D.; Ow, H.; Burns, A.; DeStanchina, E.; Longo, V.; Herz, E.; Iyer, S.; Wolchok, J.; Larson, S.M.; Wiesner, U.; Bradbury, M.S. Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma. J. Clin. Invest., 2011, 121(7), 2768-2780.
[http://dx.doi.org/10.1172/JCI45600] [PMID: 21670497]
[72]
Liu, J.; Yu, M.; Zhou, C.; Yang, S.; Ning, X.; Zheng, J. Passive tumor targeting of renal-clearable luminescent gold nanoparticles: long tumor retention and fast normal tissue clearance. J. Am. Chem. Soc., 2013, 135(13), 4978-4981.
[http://dx.doi.org/10.1021/ja401612x] [PMID: 23506476]
[73]
Heo, G.S.; Zhao, Y.; Sultan, D.; Zhang, X.; Detering, L.; Luehmann, H.P.; Zhang, X.; Li, R.; Choksi, A.; Sharp, S.; Levingston, S.; Primeau, T.; Reichert, D.E.; Sun, G.; Razani, B.; Li, S.; Weilbaecher, K.N.; Dehdashti, F.; Wooley, K.L.; Liu, Y. Assessment of copper nanoclusters for accurate in vivo tumor imaging and potential for translation. ACS Appl. Mater. Interfaces, 2019, 11(22), 19669-19678.
[http://dx.doi.org/10.1021/acsami.8b22752] [PMID: 31074257]
[74]
Gao, F.; Cai, P.; Yang, W.; Xue, J.; Gao, L.; Liu, R.; Wang, Y.; Zhao, Y.; He, X.; Zhao, L.; Huang, G.; Wu, F.; Zhao, Y.; Chai, Z.; Gao, X. Ultrasmall [(64)Cu]Cu nanoclusters for targeting orthotopic lung tumors using accurate positron emission tomography imaging. ACS Nano, 2015, 9(5), 4976-4986.
[http://dx.doi.org/10.1021/nn507130k] [PMID: 25919205]
[75]
Bazak, R.; Houri, M.; El Achy, S.; Kamel, S.; Refaat, T. Cancer active targeting by nanoparticles: A comprehensive review of literature. J. Cancer Res. Clin. Oncol., 2015, 141(5), 769-784.
[http://dx.doi.org/10.1007/s00432-014-1767-3] [PMID: 25005786]
[76]
Pandya, A.; Lad, A.N.; Singh, S.P.; Shanker, R. DNA assembled metal nanoclusters: Synthesis to novel applications. RSC Advances, 2016, 6(114), 113095-113114.
[http://dx.doi.org/10.1039/C6RA24098D]
[77]
Chen, F.; Ma, K.; Madajewski, B.; Zhuang, L.; Zhang, L.; Rickert, K.; Marelli, M.; Yoo, B.; Turker, M.Z.; Overholtzer, M.; Quinn, T.P.; Gonen, M.; Zanzonico, P.; Tuesca, A.; Bowen, M.A.; Norton, L.; Subramony, J.A.; Wiesner, U.; Bradbury, M.S. Ultrasmall targeted nanoparticles with engineered antibody fragments for imaging detection of HER2-overexpressing breast cancer. Nat. Commun., 2018, 9(1), 4141.
[http://dx.doi.org/10.1038/s41467-018-06271-5] [PMID: 30297810]
[78]
Phillips, E.; Penate-Medina, O.; Zanzonico, P.B.; Carvajal, R.D.; Mohan, P.; Ye, Y.; Humm, J.; Gönen, M.; Kalaigian, H.; Schöder, H.; Strauss, H.W.; Larson, S.M.; Wiesner, U.; Bradbury, M.S. Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe. Sci. Transl. Med., 2014, 6(260)260ra149
[http://dx.doi.org/10.1126/scitranslmed.3009524] [PMID: 25355699]
[79]
Li, Q.; Pan, Y.; Chen, T.; Du, Y.; Ge, H.; Zhang, B.; Xie, J.; Yu, H.; Zhu, M. Design and mechanistic study of a novel gold nanocluster-based drug delivery system. Nanoscale, 2018, 10(21), 10166-10172.
[http://dx.doi.org/10.1039/C8NR02189A] [PMID: 29786738]
[80]
Zheng, K.; Setyawati, M.I.; Leong, D.T.; Xie, J. Antimicrobial gold nanoclusters. ACS Nano, 2017, 11(7), 6904-6910.
[http://dx.doi.org/10.1021/acsnano.7b02035] [PMID: 28595000]
[81]
Zhang, X.D.; Luo, Z.; Chen, J.; Shen, X.; Song, S.; Sun, Y.; Fan, S.; Fan, F.; Leong, D.T.; Xie, J. Ultrasmall Au(10-12)(SG)(10-12) nanomolecules for high tumor specificity and cancer radiotherapy. Adv. Mater., 2014, 26(26), 4565-4568.
[http://dx.doi.org/10.1002/adma.201400866] [PMID: 24817169]
[82]
Xie, Y.; Liu, Y.; Yang, J.; Liu, Y.; Hu, F.; Zhu, K.; Jiang, X. Gold nanoclusters for targeting methicillin-resistant staphylococcus aureus in vivo. Angew. Chem. Int. Ed. Engl., 2018, 57(15), 3958-3962.
[http://dx.doi.org/10.1002/anie.201712878] [PMID: 29423995]
[83]
Porto, V.; Borrajo, E.; Buceta, D.; Carneiro, C.; Huseyinova, S.; Domínguez, B.; Borgman, K.J.E.; Lakadamyali, M.; Garcia-Parajo, M.F.; Neissa, J.; García-Caballero, T.; Barone, G.; Blanco, M.C.; Busto, N.; García, B.; Leal, J.M.; Blanco, J.; Rivas, J.; López-Quintela, M.A.; Domínguez, F. Silver atomic quantum clusters of three atoms for cancer therapy: targeting chromatin compaction to increase the therapeutic index of chemotherapy. Adv. Mater., 2018, 30(33)e1801317
[http://dx.doi.org/10.1002/adma.201801317] [PMID: 29974518]
[84]
Ni, D.; Jiang, D.; Kutyreff, C.J.; Lai, J.; Yan, Y.; Barnhart, T.E.; Yu, B. Molybdenum-based nanoclusters act as antioxidants and ameliorate acute kidney injury in mice. Nat. Commun., 2018, 9, 1.
[85]
Xia, H.; Li, F.; Hu, X.; Park, W.; Wang, S.; Jang, Y.; Du, Y.; Baik, S.; Cho, S.; Kang, T.; Kim, D.H.; Ling, D.; Hui, K.M.; Hyeon, T. pH-sensitive Pt nanocluster assembly overcomes cisplatin resistance and heterogeneous stemness of hepatocellular carcinoma. ACS Cent. Sci., 2016, 2(11), 802-811.
[http://dx.doi.org/10.1021/acscentsci.6b00197] [PMID: 27924308]
[86]
Mezger, U.; Jendrewski, C.; Bartels, M. Navigation in surgery. Langenbecks Arch. Surg., 2013, 398(4), 501-514.
[http://dx.doi.org/10.1007/s00423-013-1059-4] [PMID: 23430289]
[87]
Li, C.H.; Kuo, T.R.; Su, H.J.; Lai, W.Y.; Yang, P.C.; Chen, J.S.; Wang, D.Y.; Wu, Y.C.; Chen, C.C. Fluorescence-guided probes of aptamer-targeted gold nanoparticles with computed tomography imaging accesses for in vivo tumor resection. Sci. Rep., 2015, 5, 15675.
[http://dx.doi.org/10.1038/srep15675] [PMID: 26507179]
[88]
Zhou, F.; Feng, B.; Yu, H.; Wang, D.; Wang, T.; Liu, J.; Meng, Q.; Wang, S.; Zhang, P.; Zhang, Z.; Li, Y. Cisplatin prodrug-conjugated gold nanocluster for fluorescence imaging and targeted therapy of the breast cancer. Theranostics, 2016, 6(5), 679-687.
[http://dx.doi.org/10.7150/thno.14556] [PMID: 27022415]
[89]
Liu, Y.; Bhattarai, P.; Dai, Z.; Chen, X. Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer. Chem. Soc. Rev., 2019, 48(7), 2053-2108.
[http://dx.doi.org/10.1039/C8CS00618K] [PMID: 30259015]
[90]
Song, J.; Yang, X.; Jacobson, O.; Huang, P.; Sun, X.; Lin, L.; Yan, X.; Niu, G.; Ma, Q.; Chen, X. Ultrasmall gold nanorod vesicles with enhanced tumor accumulation and fast excretion from the body for cancer therapy. Adv. Mater., 2015, 27(33), 4910-4917.
[http://dx.doi.org/10.1002/adma.201502486] [PMID: 26198622]
[91]
Wang, Z.; Huang, P.; Jacobson, O.; Wang, Z.; Liu, Y.; Lin, L.; Lin, J.; Lu, N.; Zhang, H.; Tian, R.; Niu, G.; Liu, G.; Chen, X. Biomineralization-inspired synthesis of copper sulfide-ferritin nanocages as cancer theranostics. ACS Nano, 2016, 10(3), 3453-3460.
[http://dx.doi.org/10.1021/acsnano.5b07521] [PMID: 26871955]
[92]
Zhou, M.; Li, J.; Liang, S.; Sood, A.K.; Liang, D.; Li, C. CuS nanodots with ultrahigh efficient renal clearance for positron emission tomography imaging and image-guided photothermal therapy. ACS Nano, 2015, 9(7), 7085-7096.
[http://dx.doi.org/10.1021/acsnano.5b02635] [PMID: 26098195]
[93]
Shen, Z.; Chen, T.; Ma, X.; Ren, W.; Zhou, Z.; Zhu, G.; Zhang, A.; Liu, Y.; Song, J.; Li, Z.; Ruan, H.; Fan, W.; Lin, L.; Munasinghe, J.; Chen, X.; Wu, A. Multifunctional theranostic nanoparticles based on exceedingly small magnetic iron oxide nanoparticles for T1-weighted magnetic resonance imaging and chemotherapy. ACS Nano, 2017, 11(11), 10992-11004.
[http://dx.doi.org/10.1021/acsnano.7b04924] [PMID: 29039917]
[94]
Yu, X.; Li, A.; Zhao, C.; Yang, K.; Chen, X.; Li, W. Ultrasmall semimetal nanoparticles of bismuth for dual-modal computed tomography/photoacoustic imaging and synergistic thermoradiotherapy. ACS Nano, 2017, 11(4), 3990-4001.
[http://dx.doi.org/10.1021/acsnano.7b00476] [PMID: 28395135]
[95]
Guo, Z.; Chen, M.; Peng, C.; Mo, S.; Shi, C.; Fu, G.; Wen, X.; Zhuang, R.; Su, X.; Liu, T.; Zheng, N.; Zhang, X. pH-sensitive radiolabeled and superfluorinated ultra-small palladium nanosheet as a high-performance multimodal platform for tumor theranostics. Biomaterials, 2018, 179, 134-143.
[http://dx.doi.org/10.1016/j.biomaterials.2018.06.040 PMID: 29981950]
[96]
Hua, X.W.; Bao, Y.W.; Zeng, J.; Wu, F.G. Ultrasmall all-in-one nanodots formed via carbon dot-mediated and albumin-based synthesis: multimodal imaging-guided and mild laser-enhanced cancer therapy. ACS Appl. Mater. Interfaces, 2018, 10(49), 42077-42087.
[http://dx.doi.org/10.1021/acsami.8b16065] [PMID: 30403472]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version362msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[03:13:31] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[03:13:31] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[03:13:31] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[03:13:31] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (90.36ms)time
  • Application (271ms)time
  • 1 x Application (75.02%)
    271ms
    1 x Booting (24.98%)
    90.36ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    37 statements were executed, 4 of which were duplicates, 33 unique. Show only duplicated185ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('221967817','',1,1739848411,1739848411) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1739848411
      950μsalphaeurekaselec_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 ('221967817','/article/103330',1,1739848411,1739848411)
      180μsalphaeurekaselec_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 >= 221967817 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 221967817) 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 >= 221967817 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 221967817) 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 >= 221967817 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 221967817) 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 >= 221967817 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 221967817) 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 >= 221967817 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 221967817) 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 >= 221967817 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 221967817) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 221967817 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 221967817) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 221967817 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 221967817) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 221967817 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 221967817) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 221967817 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 221967817) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 221967817 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 221967817) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 221967817 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 221967817) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 221967817 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 221967817) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 221967817 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 221967817) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 221967817 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 221967817) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 221967817 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 221967817) limit 1
      19.39msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 221967817
      • 1: 221967817
      • 2: 221967817
      • 3: 221967817
      • 4: 221967817
      • 5: 221967817
      • 6: 221967817
      • 7: 221967817
      • 8: 221967817
      • 9: 221967817
      • 10: 221967817
      • 11: 221967817
      • 12: 221967817
      • 13: 221967817
      • 14: 221967817
      • 15: 221967817
      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=103330
      870μsalphaeurekaselec_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` = 4 limit 1
      980μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 4
      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=4) and sj.journal_id!=4 group by `j`.`nid`) as `aggregate_table`
      800μsalphaeurekaselec_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=4) and sj.journal_id!=4 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      710μsalphaeurekaselec_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=4) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      2.94msalphaeurekaselec_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=4) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      2.52msalphaeurekaselec_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` = '103330'
      1.68msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 103330
      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` = '103330'
      5.84msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 103330
      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` = '103330' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.69msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 103330
      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
      280μsalphaeurekaselec_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
      650μsalphaeurekaselec_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 = 4 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      53.13msalphaeurekaselec_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 = 4 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      14.64msalphaeurekaselec_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 = 4 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      8.93msalphaeurekaselec_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` = 103330 limit 1
      260μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 103330
      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 = 103330 and content_type = 'article' order by status desc limit 1
      320μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid article_nid,a.title article_title,j.title journal_title from content_by_diseases cd inner join article a on a.article_id=cd.content_id inner join journal j on j.journal_id=a.journal_id where cd.pid = 16 and cd.sub_disease_id = 454 and content_id!=103330 and cd.content_type = 'article' order by rand() limit 20
      41.37msalphaeurekaselec_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` = 177911 limit 1
      340μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 177911
      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
      260μsalphaeurekaselec_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` = 'CAC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      360μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CAC
      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 = '103330' 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) )
      460μsalphaeurekaselec_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 = '10449' 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) )
      430μsalphaeurekaselec_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 = '2918' 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) )
      350μsalphaeurekaselec_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 <= 221967817 and j.to_ip >=221967817 )) and ((j.from_date <= 1739848411 and j.to_date >= 1739848411 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2918) 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 <= 221967817 and j.to_ip >=221967817 )) and ((j.from_date <= 1739848411 and j.to_date >= 1739848411 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2918) 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 <= 221967817 and j.to_ip >=221967817 )) and ((j.from_date <= 1739848411 and j.to_date >= 1739848411 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2918)
      16.09msalphaeurekaselec_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 <= 221967817 and j.to_ip >=221967817 )) and ((j.from_date <= 1739848411 and j.to_date >= 1739848411 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10449) 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 <= 221967817 and j.to_ip >=221967817 )) and ((j.from_date <= 1739848411 and j.to_date >= 1739848411 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10449) 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 <= 221967817 and j.to_ip >=221967817 )) and ((j.from_date <= 1739848411 and j.to_date >= 1739848411 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 10449)
      610μsalphaeurekaselec_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 <= 221967817 and j.to_ip >=221967817 )) and ((j.from_date <= 1739848411 and j.to_date >= 1739848411 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 103330) 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 <= 221967817 and j.to_ip >=221967817 )) and ((j.from_date <= 1739848411 and j.to_date >= 1739848411 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 103330) 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 <= 221967817 and j.to_ip >=221967817 )) and ((j.from_date <= 1739848411 and j.to_date >= 1739848411 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 103330)
      710μsalphaeurekaselec_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` < '287' and is_uploaded = 1 and issue_id = 10449 order by cast(first_page as SIGNED) desc limit 1
      740μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 287
      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` > '301' and is_uploaded = 1 and issue_id = 10449 order by cast(first_page as SIGNED) asc limit 1
      690μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 301
      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'
      230μsalphaeurekaselec_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
      210μsalphaeurekaselec_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` = 103330 limit 1
      2.2msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 103330
      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` = 4 and `b`.`banner_from_date` <= 1739848411 and `b`.`banner_to_date` >= 1739848411 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.13msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 4
      • 3: 1739848411
      • 4: 1739848411
      • 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` = 4 and `b`.`banner_from_date` <= 1739848411 and `b`.`banner_to_date` >= 1739848411 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.06msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 4
      • 3: 1739848411
      • 4: 1739848411
      • 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='32489a0822cd4c5be224f3e08a2d72c6'
      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\MultiLanguage
    1MultiLanguage.php#?
        _token
        7iz1RIgkoq2NVXq2P9KDMzdNDNpSavAEeJovvIYX
        uc_cart_id
        32489a0822cd4c5be224f3e08a2d72c6
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/103330" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/103330
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:9 [ "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6InpzcUdycmtvY1BQSnJIVW1Wd3AyNGc9PSIsInZhbHVlIjoiak8rSWQvZ3JYM3BucEFDcFN1cjk0UzBEb2F2WEZpc3Q2eHNYdldLVUR6WGNlb1lHQ1NMejBZa01iUWRrTmZnYiIsIm1hYyI6IjZkMjEyOWMyNmUzNmNjYmZkZGI0ZWZlZmM2OTM3NzIwZDgxY2ZiMTM4ZTk3NWEzODQ0ZmE5OTk2MGYyZjVhZTciLCJ0YWciOiIifQ%3D%3Dwayfindertarget=eyJpdiI6InpzcUdycmtvY1BQSnJIVW1Wd3AyNGc9PSIsInZhbHVlIjoiak8rSWQvZ3JYM3BucEFDcFN1cjk0UzBEb2F2WEZpc3Q2eHNYdldLVUR6WGNlb1lHQ1NMejBZa01iUWRrTmZnYiIs" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 18 Feb 2025 03:13:31 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6ImV5c0tCLzJtWHR2VkhldXlGVTNyd3c9PSIsInZhbHVlIjoidTc1Y0RyUGp1ZDBJWXZvVWhvQkR4N3oyYkNHVFhONHdZVmE3Qkg3a0tSRGZqM0ZPNy9QY09rZXlnWGJDZmpQZGpidXJUVVVWY1VZV241N2FEaXg2TnpOamVucmdpMis4azYwQnpMeGRnbWQ1Vy9HVldBOFdDL1QxaDRoM2tMS3MiLCJtYWMiOiJmNDNlMjBhYzBjYjM4ZmE1ZDM4MTQ2YWJkOTJlNTM4ODA2OTU2ODdhMDU0NjI1NTgzMjI1NDc4ZDhkYWI5OGJiIiwidGFnIjoiIn0%3D; expires=Thu, 20 Feb 2025 15:13:31 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6ImV5c0tCLzJtWHR2VkhldXlGVTNyd3c9PSIsInZhbHVlIjoidTc1Y0RyUGp1ZDBJWXZvVWhvQkR4N3oyYkNHVFhONHdZVmE3Qkg3a0tSRGZqM0ZPNy9QY09rZXlnWGJDZmpQZGpidXJUV" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImhzdmNUZTViekgzcXozb2pyYzFEdWc9PSIsInZhbHVlIjoia09YWEdwYUtGOHpNK2J1dk5aaGlQcFhjbGFmbmpaWWZ3djd3cFdES3NGWHNGR1pENXdYZ09SNnVCTDI4aDVKOTBvSGMzMGlIUVNNbjZZT0dDT1NyZ1k0ZzllK1B1dzBJejZSVDcra1ZmZ0djZ01WM2p3MnVkSERNazV6SFpuWDIiLCJtYWMiOiIwYmExNTA2ZDAyNmNmOWFiZWIyYmI5YzMzZDdjYzgyNDZhZTIzMjRkYWJlNDJmMmY2ZDVkYTYxYjJlMmZkMjY2IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6ImhzdmNUZTViekgzcXozb2pyYzFEdWc9PSIsInZhbHVlIjoia09YWEdwYUtGOHpNK2J1dk5aaGlQcFhjbGFmbmpaWWZ3djd3cFdES3NGWHNGR1pENXdYZ09SNnV" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6ImV5c0tCLzJtWHR2VkhldXlGVTNyd3c9PSIsInZhbHVlIjoidTc1Y0RyUGp1ZDBJWXZvVWhvQkR4N3oyYkNHVFhONHdZVmE3Qkg3a0tSRGZqM0ZPNy9QY09rZXlnWGJDZmpQZGpidXJUVVVWY1VZV241N2FEaXg2TnpOamVucmdpMis4azYwQnpMeGRnbWQ1Vy9HVldBOFdDL1QxaDRoM2tMS3MiLCJtYWMiOiJmNDNlMjBhYzBjYjM4ZmE1ZDM4MTQ2YWJkOTJlNTM4ODA2OTU2ODdhMDU0NjI1NTgzMjI1NDc4ZDhkYWI5OGJiIiwidGFnIjoiIn0%3D; expires=Thu, 20-Feb-2025 15:13:31 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6ImV5c0tCLzJtWHR2VkhldXlGVTNyd3c9PSIsInZhbHVlIjoidTc1Y0RyUGp1ZDBJWXZvVWhvQkR4N3oyYkNHVFhONHdZVmE3Qkg3a0tSRGZqM0ZPNy9QY09rZXlnWGJDZmpQZGpidXJUV" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImhzdmNUZTViekgzcXozb2pyYzFEdWc9PSIsInZhbHVlIjoia09YWEdwYUtGOHpNK2J1dk5aaGlQcFhjbGFmbmpaWWZ3djd3cFdES3NGWHNGR1pENXdYZ09SNnVCTDI4aDVKOTBvSGMzMGlIUVNNbjZZT0dDT1NyZ1k0ZzllK1B1dzBJejZSVDcra1ZmZ0djZ01WM2p3MnVkSERNazV6SFpuWDIiLCJtYWMiOiIwYmExNTA2ZDAyNmNmOWFiZWIyYmI5YzMzZDdjYzgyNDZhZTIzMjRkYWJlNDJmMmY2ZDVkYTYxYjJlMmZkMjY2IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6ImhzdmNUZTViekgzcXozb2pyYzFEdWc9PSIsInZhbHVlIjoia09YWEdwYUtGOHpNK2J1dk5aaGlQcFhjbGFmbmpaWWZ3djd3cFdES3NGWHNGR1pENXdYZ09SNnV" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "7iz1RIgkoq2NVXq2P9KDMzdNDNpSavAEeJovvIYX" "uc_cart_id" => "32489a0822cd4c5be224f3e08a2d72c6" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/103330" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-18 03:13:31GET/article/103330414371