CoChat
Sign Up
Cited by 54Advanced Glycation End Products researchAldose Reductase and TaurinePancreatic function and diabetes

Elevated 4-hydroxynonenal induces hyperglycaemia via Aldh3a1 loss in zebrafish and associates with diabetes progression in humans

Open access
Lou, Bowen, Boger, Mike, Bennewitz, Katrin, Sticht, Carsten, Kopf, Stefan, Morgenstern, Jakob, Fleming, Thomas, Hell, Rüdiger +3 more·2020·Redox Biology
DOI 10.1016/j.redox.2020.101723PMC PMC7519378
Open this paper in CoChat — free account

Abstract

Increased methylglyoxal (MG) formation is associated with diabetes and its complications. In zebrafish, knockout of the main MG detoxifying system Glyoxalase 1, led to limited MG elevation but significantly elevated aldehyde dehydrogenases (ALDH) activity and aldh3a1 expression, suggesting the compensatory role of Aldh3a1 in diabetes. To evaluate the function of Aldh3a1 in glucose homeostasis and diabetes, aldh3a1−/− zebrafish mutants were generated using CRISPR-Cas9. Vasculature and pancreas morphology were analysed by zebrafish transgenic reporter lines. Corresponding reactive carbonyl species (RCS), glucose, transcriptome and metabolomics screenings were performed and ALDH activity was measured for further verification. Aldh3a1−/− zebrafish larvae displayed retinal vasodilatory alterations, impaired glucose homeostasis, which can be aggravated via pdx1 silencing induced hyperglycaemia. Unexpectedly, MG was not altered, but 4-hydroxynonenal (4-HNE), another prominent lipid peroxidation RCS exhibited high affinity with Aldh3a1, was increased in aldh3a1 mutants. 4-HNE was responsible for the retinal phenotype via pancreas disruption induced hyperglycaemia and can be rescued via l-Carnosine treatment. Furthermore, in type 2 diabetic patients, serum 4-HNE was increased and correlated with disease progression. Thus, our data suggest impaired 4-HNE detoxification and elevated 4-HNE concentration as biomarkers but also the possible inducers for diabetes, from genetic susceptibility to the pathological progression.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.redox.2020.101723

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 64

  1. [1]Saeedi P. Petersohn I. Salpea P. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9(th) edition Diabetes Res. Clin. Pract. 157 2019 107843 10.1016/j.diabres.2019.107843 [published Online First: 2019/09/14] 31518657 · DOI · Paper page
  2. [3]Congdon N.G. Friedman D.S. Lietman T. Important causes of visual impairment in the world today J. Am. Med. Assoc. 290 15 2003 2057 2060 10.1001/jama.290.15.2057 [published Online First: 2003/10/16] 14559961 · DOI
  3. [4]Fenwick E.K. Pesudovs K. Rees G. The impact of diabetic retinopathy: understanding the patient's perspective Br. J. Ophthalmol. 95 6 2011 774 782 10.1136/bjo.2010.191312 20940313 · DOI
  4. [5]Thornalley P.J. Protein and nucleotide damage by glyoxal and methylglyoxal in physiological systems--role in ageing and disease Drug Metabol. Drug Interact. 23 1–2 2008 125 150 10.1515/dmdi.2008.23.1-2.125 [published Online First: 2008/06/07] 18533367 PMC2649415 · DOI
  5. [6]Rabbani N. Thornalley P.J. Glyoxalase 1 modulation in obesity and diabetes Antioxid Redox Signal 30 3 2019 354 374 10.1089/ars.2017.7424 [published Online First: 2017/11/22] 29160087 · DOI · Paper page
  6. [7]Beisswenger P.J. Howell S.K. Touchette A.D. Metformin reduces systemic methylglyoxal levels in type 2 diabetes Diabetes 48 1 1999 198 202 10.2337/diabetes.48.1.198 [published Online First: 1999/01/19] 9892243 · DOI
  7. [8]Berner A.K. Brouwers O. Pringle R. Protection against methylglyoxal-derived AGEs by regulation of glyoxalase 1 prevents retinal neuroglial and vasodegenerative pathology Diabetologia 55 3 2012 845 854 10.1007/s00125-011-2393-0 [published Online First: 2011/12/07] 22143324 · DOI
  8. [9]Curtis T.M. Hamilton R. Yong P.H. Muller glial dysfunction during diabetic retinopathy in rats is linked to accumulation of advanced glycation end-products and advanced lipoxidation end-products Diabetologia 54 3 2011 690 698 10.1007/s00125-010-1971-x [published Online First: 2010/12/01] 21116609 · DOI
  9. [10]Vander Jagt D.L. Hunsaker L.A. Methylglyoxal metabolism and diabetic complications: roles of aldose reductase, glyoxalase-I, betaine aldehyde dehydrogenase and 2-oxoaldehyde dehydrogenase Chem. Biol. Interact. 143–144 2003 341 351 10.1016/s0009-2797(02)00212-0 12604221 · DOI
  10. [11]Baba S.P. Barski O.A. Ahmed Y. Reductive metabolism of AGE precursors: a metabolic route for preventing AGE accumulation in cardiovascular tissue Diabetes 58 11 2009 2486 2497 10.2337/db09-0375 [published Online First: 2009/08/05] 19651811 PMC2768164 · DOI
  11. [12]Lodd E. Wiggenhauser L.M. Morgenstern J. The combination of loss of glyoxalase 1 and obesity results in hyperglycemia JCI Insight 4 12 2019 10.1172/jci.insight.126154 PMC6629122 31217350 · DOI
  12. [13]Vasiliou V. Thompson D.C. Smith C. Aldehyde dehydrogenases: from eye crystallins to metabolic disease and cancer stem cells Chem. Biol. Interact. 202 1–3 2013 2 10 10.1016/j.cbi.2012.10.026 [published Online First: 2012/11/20] 23159885 PMC4128326 · DOI
  13. [14]Schaur R.J. Siems W. Bresgen N. 4-Hydroxy-nonenal-A bioactive lipid peroxidation product Biomolecules 5 4 2015 2247 2337 10.3390/biom5042247 [published Online First: 2015/10/06] 26437435 PMC4693237 · DOI
  14. [15]Cohen G. Riahi Y. Sunda V. Signaling properties of 4-hydroxyalkenals formed by lipid peroxidation in diabetes Free Radic. Biol. Med. 65 2013 978 987 10.1016/j.freeradbiomed.2013.08.163 [published Online First: 2013/08/27] 23973638 · DOI
  15. [16]Benedetti E. D'Angelo B. Cristiano L. Involvement of peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) in BDNF signaling during aging and in Alzheimer disease: possible role of 4-hydroxynonenal (4-HNE) Cell Cycle 13 8 2014 1335 1344 10.4161/cc.28295 [published Online First: 2014/03/14] 24621497 PMC4049970 · DOI
  16. [17]Dalleau S. Baradat M. Gueraud F. Cell death and diseases related to oxidative stress: 4-hydroxynonenal (HNE) in the balance Cell Death Differ. 20 12 2013 1615 1630 10.1038/cdd.2013.138 [published Online First: 2013/10/08] 24096871 PMC3824598 · DOI · Paper page
  17. [18]Zhong H. Yin H. Role of lipid peroxidation derived 4-hydroxynonenal (4-HNE) in cancer: focusing on mitochondria Redox Biol 4 2015 193 199 10.1016/j.redox.2014.12.011 [published Online First: 2015/01/20] 25598486 PMC4803793 · DOI
  18. [19]Pashkow F.J. Oxidative stress and inflammation in heart disease: do antioxidants have a role in treatment and/or prevention? Int. J. Inflamm. 2011 2011 514623 10.4061/2011/514623 [published Online First: 2011/08/24] PMC3157078 21860805 · DOI
  19. [20]Okamoto K. Toyokuni S. Uchida K. Formation of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins in human renal-cell carcinoma Int. J. Canc. 58 6 1994 825 829 10.1002/ijc.2910580613 [published Online First: 1994/09/15] 7523311 · DOI
  20. [21]Sasson S. 4-Hydroxyalkenal-activated PPARdelta mediates hormetic interactions in diabetes Biochimie 136 2017 85 89 10.1016/j.biochi.2016.10.007 [published Online First: 2016/10/26] 27768859 · DOI
  21. [22]Sasson S. Nutrient overload, lipid peroxidation and pancreatic beta cell function Free Radic. Biol. Med. 111 2017 102 109 10.1016/j.freeradbiomed.2016.09.003 [published Online First: 2016/09/08] 27600453 · DOI
  22. [23]Liu G. Ji W. Huang J. 4-HNE expression in diabetic rat kidneys and the protective effects of probucol J. Endocrinol. Invest. 39 8 2016 865 873 10.1007/s40618-015-0428-y [published Online First: 2016/02/03] 26830905 · DOI
  23. [24]Akude E. Zherebitskaya E. Roy Chowdhury S.K. 4-Hydroxy-2-nonenal induces mitochondrial dysfunction and aberrant axonal outgrowth in adult sensory neurons that mimics features of diabetic neuropathy Neurotox. Res. 17 1 2010 28 38 10.1007/s12640-009-9074-5 [published Online First: 2009/06/27] 19557324 PMC2894940 · DOI
  24. [25]Mori A. Takei T. Sakamoto K. 4-Hydroxy-2-nonenal attenuates beta2-adrenoceptor-mediated vasodilation of rat retinal arterioles Naunyn-Schmiedeberg’s Arch. Pharmacol. 388 5 2015 575 582 10.1007/s00210-015-1099-0 [published Online First: 2015/02/20] 25693977 · DOI
  25. [26]Pappa A. Brown D. Koutalos Y. Human aldehyde dehydrogenase 3A1 inhibits proliferation and promotes survival of human corneal epithelial cells J. Biol. Chem. 280 30 2005 27998 28006 10.1074/jbc.M503698200 [published Online First: 2005/05/21] 15905174 · DOI
  26. [27]Marchitti S.A. Brocker C. Stagos D. Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily Expet Opin. Drug Metabol. Toxicol. 4 6 2008 697 720 10.1517/17425255.4.6.697 [published Online First: 2008/07/10] PMC2658643 18611112 · DOI
  27. [28]Voulgaridou G.P. Tsochantaridis I. Tolkas C. Aldehyde dehydrogenase 3A1 confers oxidative stress resistance accompanied by altered DNA damage response in human corneal epithelial cells Free Radic. Biol. Med. 2020 10.1016/j.freeradbiomed.2020.01.183 [published Online First: 2020/02/02] 32006654 · DOI
  28. [29]Lassen N. Bateman J.B. Estey T. Multiple and additive functions of ALDH3A1 and ALDH1A1: cataract phenotype and ocular oxidative damage in Aldh3a1(-/-)/Aldh1a1(-/-) knock-out mice J. Biol. Chem. 282 35 2007 25668 25676 10.1074/jbc.M702076200 [published Online First: 2007/06/15] 17567582 PMC2253645 · DOI
  29. [30]Holmes R.S. Hempel J. Comparative studies of vertebrate aldehyde dehydrogenase 3: sequences, structures, phylogeny and evolution. Evidence for a mammalian origin for the ALDH3A1 gene Chem. Biol. Interact. 191 1–3 2011 113 121 10.1016/j.cbi.2011.01.014 21296057 · DOI
  30. [31]Agalou A. Thrapsianiotis M. Angelis A. Identification of novel melanin Synthesis inhibitors from crataegus pycnoloba using an in vivo zebrafish phenotypic assay Front. Pharmacol. 9 2018 265 10.3389/fphar.2018.00265 29632489 PMC5879087 · DOI
  31. [33]Cook O.F. The mendelian inheritance of mutations Science 28 707 1908 86 88 10.1126/science.28.707.86 17778480 · DOI
  32. [34]Jorgens K. Stoll S.J. Pohl J. High tissue glucose alters intersomitic blood vessels in zebrafish via methylglyoxal targeting the VEGF receptor signaling cascade Diabetes 64 1 2015 213 225 10.2337/db14-0352 25092676 · DOI
  33. [35]Babu D.A. Deering T.G. Mirmira R.G. A feat of metabolic proportions: pdx1 orchestrates islet development and function in the maintenance of glucose homeostasis Mol. Genet. Metabol. 92 1–2 2007 43 55 10.1016/j.ymgme.2007.06.008 [published Online First: 2007/07/31] PMC2042521 17659992 · DOI
  34. [36]Bek T. Diameter changes of retinal vessels in diabetic retinopathy Curr. Diabetes Rep. 17 10 2017 82 10.1007/s11892-017-0909-9 [published Online First: 2017/08/10] 28791532 · DOI
  35. [37]Kimmel R.A. Meyer D. Molecular regulation of pancreas development in zebrafish Methods Cell Biol. 100 2010 261 280 10.1016/B978-0-12-384892-5.00010-4 21111221 · DOI
  36. [38]Pisharath H. Rhee J.M. Swanson M.A. Targeted ablation of beta cells in the embryonic zebrafish pancreas using E. coli nitroreductase Mech. Dev. 124 3 2007 218 229 10.1016/j.mod.2006.11.005 17223324 PMC2583263 · DOI
  37. [40]Papasani M.R. Robison B.D. Hardy R.W. Early developmental expression of two insulins in zebrafish (Danio rerio) Physiol. Genom. 27 1 2006 79 85 10.1152/physiolgenomics.00012.2006 [published Online First: 2006/07/20] 16849636 · DOI · Paper page
  38. [41]Breitzig M. Bhimineni C. Lockey R. 4-Hydroxy-2-nonenal: a critical target in oxidative stress? Am. J. Physiol. Cell Physiol. 311 4 2016 C537 C543 10.1152/ajpcell.00101.2016 [published Online First: 2016/07/08] 27385721 PMC5129750 · DOI
  39. [42]Noguchi K. Ali T.F.S. Miyoshi J. Neuroprotective effects of a novel carnosine-hydrazide derivative on hippocampal CA1 damage after transient cerebral ischemia Eur. J. Med. Chem. 163 2019 207 214 10.1016/j.ejmech.2018.11.060 30522055 · DOI
  40. [43]Wiggenhauser L.M. Qi H. Stoll S.J. Activation of retinal angiogenesis in hyperglycemic pdx1 (-/-) zebrafish mutants Diabetes 2020 10.2337/db19-0873 32139597 · DOI
  41. [44]Simmons K.M. Michels A.W. Type 1 diabetes: a predictable disease World J. Diabetes 6 3 2015 380 390 10.4239/wjd.v6.i3.380 [published Online First: 2015/04/22] 25897349 PMC4398895 · DOI
  42. [45]Sun T. Han X. Death versus dedifferentiation: the molecular bases of beta cell mass reduction in type 2 diabetes Semin. Cell Dev. Biol. 103 2020 76 82 10.1016/j.semcdb.2019.12.002 31831356 · DOI
  43. [46]Cohen G. Riahi Y. Shamni O. Role of lipid peroxidation and PPAR-delta in amplifying glucose-stimulated insulin secretion Diabetes 60 11 2011 2830 2842 10.2337/db11-0347 21896929 PMC3198069 · DOI
  44. [48]Oruc Y. Celik F. Ozgur G. Altered blood and aqueous humor levels of asprosin, 4-hydroxynonenal, and 8-hydroxy-deoxyguanosine in patients with diabetes mellitus and cataract with and without diabetic retinopathy Retina 2020 10.1097/IAE.0000000000002776 [published Online First: 2020/02/25] 32091490 · DOI
  45. [49]La Sala L. Mrakic-Sposta S. Tagliabue E. Circulating microRNA-21 is an early predictor of ROS-mediated damage in subjects with high risk of developing diabetes and in drug-naive T2D Cardiovasc. Diabetol. 18 1 2019 18 10.1186/s12933-019-0824-2 [published Online First: 2019/02/26] 30803440 PMC6388471 · DOI
  46. [50]Jaganjac M. Almuraikhy S. Al-Khelaifi F. Combined metformin and insulin treatment reverses metabolically impaired omental adipogenesis and accumulation of 4-hydroxynonenal in obese diabetic patients Redox Biol 12 2017 483 490 10.1016/j.redox.2017.03.012 [published Online First: 2017/03/24] 28334683 PMC5362139 · DOI
  47. [51]Xu T. Liu S. Ma T. Aldehyde dehydrogenase 2 protects against oxidative stress associated with pulmonary arterial hypertension Redox Biol 11 2017 286 296 10.1016/j.redox.2016.12.019 [published Online First: 2016/12/29] 28030785 PMC5192477 · DOI
  48. [52]Jaganjac M. Milkovic L. Gegotek A. The relevance of pathophysiological alterations in redox signaling of 4-hydroxynonenal for pharmacological therapies of major stress-associated diseases Free Radic. Biol. Med. 157 2020 128 153 10.1016/j.freeradbiomed.2019.11.023 [published Online First: 2019/11/23] 31756524 · DOI
  49. [53]Ito F. Sono Y. Ito T. Measurement and clinical significance of lipid peroxidation as a biomarker of oxidative stress: oxidative stress in diabetes, atherosclerosis, and chronic inflammation Antioxidants 8 3 2019 10.3390/antiox8030072 [published Online First: 2019/04/03] PMC6466575 30934586 · DOI · Paper page
  50. [54]Herder C. Roden M. Genetics of type 2 diabetes: pathophysiologic and clinical relevance Eur. J. Clin. Invest. 41 6 2011 679 692 10.1111/j.1365-2362.2010.02454.x [published Online First: 2011/01/05] 21198561 · DOI
  51. [55]Lawson N.D. Weinstein B.M. In vivo imaging of embryonic vascular development using transgenic zebrafish Dev. Biol. 248 2 2002 307 318 10.1006/dbio.2002.0711 12167406 · DOI
  52. [56]Flanagan-Steet H. Fox M.A. Meyer D. Neuromuscular synapses can form in vivo by incorporation of initially aneural postsynaptic specializations Development 132 20 2005 4471 4481 10.1242/dev.02044 16162647 · DOI
  53. [57]Kimmel C.B. Ballard W.W. Kimmel S.R. Stages of embryonic development of the zebrafish Dev. Dynam. 203 3 1995 253 310 10.1002/aja.1002030302 8589427 · DOI · Paper page
  54. [58]Jurczyk A. Roy N. Bajwa R. Dynamic glucoregulation and mammalian-like responses to metabolic and developmental disruption in zebrafish Gen. Comp. Endocrinol. 170 2 2011 334 345 10.1016/j.ygcen.2010.10.010 [published Online First: 2010/10/23] 20965191 PMC3014420 · DOI
  55. [59]Jao L.E. Wente S.R. Chen W. Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system Proc. Natl. Acad. Sci. U. S. A. 110 34 2013 13904 13909 10.1073/pnas.1308335110 [published Online First: 2013/08/07] 23918387 PMC3752207 · DOI
  56. [60]Hill J.T. Demarest B.L. Bisgrove B.W. Poly peak parser: method and software for identification of unknown indels using sanger sequencing of polymerase chain reaction products Dev. Dynam. 243 12 2014 1632 1636 10.1002/dvdy.24183 [published Online First: 2014/08/28] PMC4525701 25160973 · DOI
  57. [61]Jung S.H. Kim Y.S. Lee Y.R. High glucose-induced changes in hyaloid-retinal vessels during early ocular development of zebrafish: a short-term animal model of diabetic retinopathy Br. J. Pharmacol. 173 1 2016 15 26 10.1111/bph.13279 26276677 PMC4813374 · DOI
  58. [62]McLellan A.C. Thornalley P.J. Glyoxalase activity in human red blood cells fractioned by age Mech. Ageing Dev. 48 1 1989 63 71 10.1016/0047-6374(89)90026-2 2725076 · DOI
  59. [63]Tw H.B. Girke T. systemPipeR: NGS workflow and report generation environment BMC Bioinf. 17 2016 388 10.1186/s12859-016-1241-0 PMC5029110 27650223 · DOI
  60. [64]Bray N.L. Pimentel H. Melsted P. Near-optimal probabilistic RNA-seq quantification Nat. Biotechnol. 34 5 2016 525 527 10.1038/nbt.3519 27043002 · DOI · Paper page
  61. [65]Ritchie M.E. Phipson B. Wu D. Limma powers differential expression analyses for RNA-sequencing and microarray studies Nucleic Acids Res. 43 7 2015 e47 10.1093/nar/gkv007 25605792 PMC4402510 · DOI · Paper page
  62. [66]Walter W. Sanchez-Cabo F. Ricote M. GOplot: an R package for visually combining expression data with functional analysis Bioinformatics 31 17 2015 2912 2914 10.1093/bioinformatics/btv300 25964631 · DOI
  63. [67]Gu Z. Eils R. Schlesner M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data Bioinformatics 32 18 2016 2847 2849 10.1093/bioinformatics/btw313 27207943 · DOI
  64. [68]She Jianqing Yuan Zuyi Wu Yue Targeting erythropoietin protects against proteinuria in type 2 diabetic patients and in zebrafish Molecular Metabolism 8 2018 189 202 10.1016/j.molmet.2017.11.006 10.1016/j.molmet.2017.11.006 29203238 PMC5985015 · DOI

Cited by

Sorted by citations

Authors
Lou, B., Boger, M., Bennewitz, K., Sticht, C., Kopf, S., Morgenstern, J., Fleming, T., Hell, R., Yuan, Z., Nawroth, P. P., & Kroll, J.
Affiliations
  • Heidelberg University (DE)
  • University Hospital Heidelberg (DE)
  • First Affiliated Hospital of Xi'an Jiaotong University (CN)
ORCID
Venue
Redox Biology
Publisher
Elsevier BV
Published
2020-10
Volume
37
Pages
101723
ISSN
2213-2317 (ISSN-L)
DOI
10.1016/j.redox.2020.101723
PMC
PMC7519378
OpenAlex
W3085013753
Cited by
54
References
4
Citations by year
2026: 5 · 2025: 10 · 2024: 6 · 2023: 10 · 2022: 13 · 2021: 9 · 2020: 1
FWCI
5.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Redox Biology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Site cant be reached (submittedVersion, cc-by-nc-nd)
  • PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by-nc-nd)
Funders
  • China Scholarship Council
  • Deutsche Forschungsgemeinschaft
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
4-hydroxynonenal, ALDH3A1, aldehyde dehydrogenase, hyperglycemia, type 2 diabetes, glucose homeostasis, methylglyoxal, lipid peroxidation, reactive carbonyl species, retinal vasodilation, pancreatic development, PDX1, L-carnosine, diabetes biomarkers, zebrafish model
MeSH terms
Aldehyde Dehydrogenase, Aldehydes, Animals, Diabetes Mellitus, Humans, Hyperglycemia, Zebrafish, Gene Knockout Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review