Investigation Report on 'The synthesis and evaluation of near-infrared probes with barbituric acid acceptors for in vivo detection of amyloid plaques' (Chem. Commun., 2015, DOI: 10.1039/c5cc03662c)

Academic fraud report · Geng Detector

Summary

This report evaluates a 2015 ChemComm paper by Zhou et al. on near-infrared fluorescent probes for amyloid plaque imaging. The overall verdict is 'questionable' (yellow flag). Three findings are flagged: (1) Figure 2 fluorescence spectra for BBTOM-3 under multiple conditions show impossibly perfect baseline overlap in the ~400–550 nm region, inconsistent with real instrument noise and drift, suggesting over-smoothing or data substitution; (2) Figure 4 in vivo brain kinetics curves for Tg and WT mice (n=3) display error bars that are unusually uniform and symmetric, statistically improbable for such small biological samples; (3) A citation mismatch where DANIR-2c binding affinity data is attributed to reference 15 (Okamura, THK-265), while reference 16 corresponds to the authors' own DANIR paper. Severity is rated moderate for all three issues. None constitutes definitive proof of fabrication; all could in principle reflect excessive post-processing or typographical error. The findings warrant raw-data requests but stop short of formal misconduct allegations.

Verdict

Questionable (yellow flag). Three independent concerns were identified: suspicious spectral baselines, implausibly uniform in vivo error bars at n=3, and a citation/reference mismatch for a key comparator probe. None is individually conclusive, but in combination they suggest inadequate data rigor and possible post-processing that exceeds normal practice.

Key findings

Figure 2 baseline anomaly: Fluorescence spectra of BBTOM-3 across PBS, Aβ aggregates, Aβ monomers, and BSA conditions show perfectly overlapping baselines (~400–550 nm) with no visible noise or drift, which is highly atypical for real fluorometer output.
Figure 4 error bar uniformity: In vivo brain uptake curves for Tg and WT mice (n=3 per the Methods) show error bars of nearly identical magnitude and symmetric placement across all time points, inconsistent with the expected variability of small biological samples.
Citation misassignment (Page 11666): The text attributes DANIR-2c's Ki = 36.9 nM to reference 15 (Okamura et al., J. Alzheimer's Dis., 2011, on THK-265), while reference 16 is the authors' own DANIR-3 paper (M. Cui et al., J. Am. Chem. Soc., 2014). The Ki values themselves are internally consistent, suggesting a reference-number transposition rather than fabricated data.

Evidence highlights

DOI: 10.1039/c5cc03662c
Specific Ki values cited in text: DANIR-2c = 36.9 nM, MCAAD-3 = 106 nM, MAAD-3 = 354.3 nM, DMDAD-3 = 645.2 nM.
Stated sample size for in vivo imaging: n = 3 (Tg and age-matched WT mice).
Figure 2 located on page 11666; Figure 4 in vivo kinetics on page 11667.
Reference 15: N. Okamura et al. (THK-265, J. Alzheimer's Dis., 2011). Reference 16: M. Cui et al. (DANIR series, J. Am. Chem. Soc., 2014).

Notes

All findings are based on the published article text and figures only; no raw spectra, original imaging data, or laboratory records were available for inspection. The baseline and error-bar observations are statistical/spectroscopic inferences, not proven manipulation. The citation swap is most plausibly a proofreading error but, given the other concerns, warrants scrutiny. Recommended follow-up: request raw spectral files and uncropped in vivo imaging data from the corresponding authors, and consider posting the concerns on PubPeer for author response. Final determination of misconduct requires institutional investigation.