Evidence map›Paper›PMID 40129052›Full record

ArticleAngewandte Chemie (International ed. in English)2025

Imaging Heterogeneous Patterns of Aminopeptidase N Activity in Hierarchical Tissue Structures Through High-Resolution Whole-Organ 3D Mapping.

Bo Yi, Hiroyuki Yatabe, Daichi M Sakamoto, Iori Tamura, Yutaro Saito, Naoki Yamada, Ruki Ashikaga, Masafumi Kuroda, Shimpei I Kubota, Kazuki Tainaka and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Bo YiDepartment of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Hiroyuki YatabeDepartment of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Daichi M Sakamoto *Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Iori Tamura *Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Yutaro SaitoDepartment of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Naoki YamadaDepartment of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Ruki AshikagaDepartment of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Masafumi KurodaInternational Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Shimpei I KubotaDivision of Molecular Psychoimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-0815, Japan.
Kazuki TainakaDepartment of System Pathology for Neurological Disorders, Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8585, Japan.
Shinsuke SandoDepartment of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Funding

AMED JP21wm0425001AMED JP21zf0127004AMED JP223fa727001s0801Hagiwara Foundation of JapanJSPS KAKENHI JP19H00919JSPS KAKENHI JP22H02937JSPS KAKENHI JP22K19105JST Moonshot R&D Program JPMJMS2022-14MEXT Q-LEAP JPMXS0120330644Precise Measurement Technology Promotion Foundation
6 · The paper itself

Abstract

Enzymes play a crucial role in regulating physiological functions, and abnormal enzyme activity is associated with various pathological conditions. Precise imaging of enzyme activity in tissues, providing detailed spatial and quantitative information, advances our understanding of physiological and pathological processes. Despite their importance, there is still a lack of methods for high-resolution 3D imaging of enzyme activity across entire tissues. In this research, we report a methodology for high-resolution, whole-organ 3D mapping of enzyme activity, which combines tissue clearing with an activity-based covalent chemical probe. Focusing on aminopeptidase N (APN) as a representative target of peptidase, we developed ANA-o-BODIPY, an activity-based covalent fluorescent probe compatible with tissue clearing for imaging APN activity. Upon activation by APN, ANA-o-BODIPY produces a reactive intermediate, aza-quinone methide, which covalently binds to proximal proteins. This covalent probe is successfully utilized to record the location of APN activity during the tissue-clearing process. By combining the probe with tissue clearing, we have achieved high-resolution 3D mapping of APN activity across whole organs for the first time. Moreover, this advancement allowed us to visualize the heterogeneity of APN activity in individual tubular structures and to uncover the inhibitory effects of different APN inhibitors.

Indexed as

CD13 AntigensFluorescent DyesImaging, Three-DimensionalAnimalsBoron CompoundsHumansMice4,4-difluoro-4-bora-3a,4a-diaza-s-indaceneBoron CompoundsCD13 AntigensFluorescent DyesAminopeptidase NChemical probeFluorescence imagingTissue clearing

Identifiers

PMID40129052
PMCPMC12105696

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.