High total Joule heat increases the risk of post-endoscopic submucosal dissection electrocoagulation syndrome after colorectal endoscopic submucosal dissection.

BACKGROUND: We hypothesized that thermal damage accumulation during endoscopic submucosal dissection (ESD) causes the pathogenesis of post-ESD electrocoagulation syndrome (PECS). AIM: To determine the association between Joule heat and the onset of PECS. METHODS: We performed a retrospective cohort study in patients who underwent colorectal ESD from May 2013 to March 2021 in Japan. We developed a novel device that measures swift coagulation time with a sensor adjacent to the electrosurgical coagulation unit foot switch, which enabled us to calculate total Joule heat. PECS was defined as localized abdominal pain (visual analogue scale ≥ 30 mm during hospitalization or increased by ≥ 20 mm from the baseline) and fever (temperature ≥ 37.5 degrees or white blood cell count ≥ 10000 µ/L). Patients exposed to more or less than the median Joule heat value were assigned to the high and low Joule heat groups, respectively. Statistical analyses included Mann-Whitney U and chi-square tests and logistic regression and receiver operating characteristic curve (ROC) analyses. RESULTS: We evaluated 151 patients. The PECS incidence was 10.6% (16/151 cases), and all patients were followed conservatively and discharged without severe complications. In multivariate analysis, high Joule heat was an independent PECS risk factor. The area under the ROC curve showing the correlation between PECS and total Joule heat was high [0.788 (95% confidence interval: 0.666-0.909)]. CONCLUSION: Joule heat accumulation in the gastrointestinal wall is involved in the onset of PECS. ESD-related thermal damage to the peeled mucosal surface is probably a major component of the mechanism underlying PECS.

A multicolor and ratiometric fluorescent sensing platform for metal ions based on arene-metal-ion contact.

Despite continuous and active development of fluorescent metal-ion probes, their molecular design for ratiometric detection is restricted by the limited choice of available sensing mechanisms. Here we present a multicolor and ratiometric fluorescent sensing platform for metal ions based on the interaction between the metal ion and the aromatic ring of a fluorophore (arene-metal-ion, AM, coordination). Our molecular design provided the probes possessing a 1,9-bis(2'-pyridyl)-2,5,8-triazanonane as a flexible metal ion binding unit attached to a tricyclic fluorophore. This architecture allows to sense various metal ions, such as Zn(II), Cu(II), Cd(II), Ag(I), and Hg(II) with emission red-shifts. We showed that this probe design is applicable to a series of tricyclic fluorophores, which allow ratiometric detection of the metal ions from the blue to the near-infrared wavelengths. X-ray crystallography and theoretical calculations indicate that the coordinated metal ion has van der Waals contact with the fluorophore, perturbing the dye's electronic structure and ring conformation to induce the emission red-shift. A set of the probes was useful for the differential sensing of eight metal ions in a one-pot single titration via principal component analysis. We also demonstrate that a xanthene fluorophore is applicable to the ratiometric imaging of metal ions under live-cell conditions.

Fluorescence detection of metabolic activity of the fatty acid beta oxidation pathway in living cells.

Detection of metabolic activity in living cells facilitates the understanding of the cell mechanism. Here, we report a fluorescent probe that can detect fatty acid beta oxidation (FAO) in living cells. This probe is metabolically degraded by the sequential enzyme reactions of FAO and can visualize the FAO activity with turn-on fluorescence.

Reversible ratiometric detection of highly reactive hydropersulfides using a FRET-based dual emission fluorescent probe.

Hydropersulfide (R-SSH) is an important class of reactive sulfur species (RSS) involved in a variety of physiological processes in mammals. A fluorescent probe capable of real-time detection of hydropersulfide levels in living cells would be a versatile tool to elucidate its roles in cell signalling and redox homeostasis. In this paper, we report a ratiometric fluorescent probe for hydropersulfide sensing, based on a fluorescence resonance energy transfer (FRET) mechanism. This sensing mechanism involves a nucleophilic reaction of a hydropersulfide with the pyronine-unit of the probe, which modulates the intramolecular FRET efficiency to induce a dual-emission change. The reversible nature of this reaction allows us to detect increases and decreases of hydropersulfide levels in a real-time manner. The probe fluorometrically sensed highly reactive hydropersulfides, such as H2S2 and Cys-SSH, while the fluorescence response to biologically abundant cysteine and glutathione was negligible. Taking advantage of the reversible and selective sensing properties, this probe was successfully applied to the ratiometric imaging of concentration dynamics of endogenously produced hydropersulfides in living cells.

Rational Design of a Ratiometric Fluorescent Probe Based on Arene-Metal-Ion Contact for Endogenous Hydrogen Sulfide Detection in Living Cells.

We report the design and development of a fluorescent Cd(II) ion complex that is capable of the ratiometric detection of H2 S in living cells. This probe exploits the metal-ion-induced emission red shift resulting from direct contact between the aromatic ring of a fluorophore and a metal ion (i.e., arene-metal-ion or "AM" contact). The Cd(II) complex displays a large emission blue shift upon interaction with H2 S as the Cd(II) -free ligand is released by the formation of cadmium sulfide. Screening of potential ligands and fluorophores led to the discovery of a pyronine-type probe, 6⋅Cd(II) , that generated a sensitive and rapid ratio value change upon interaction with H2 S, without interference from the glutathione that is abundant in the cell. The membrane-impermeable 6⋅Cd(II) was successfully translocated into live cells by using an oligo-arginine peptide and pyrenebutylate as carriers. As such, 6⋅Cd(II) was successfully applied to the ratiometric detection of both exogenous and endogenous H2 S produced by the enzymes in living cells, thus demonstrating the utility of 6⋅Cd(II) in biological fluorescence analysis.

Development of an AND logic-gate-type fluorescent probe for ratiometric imaging of autolysosome in cell autophagy.

The concomitant detection of two biological events facilitates the highly selective and sensitive analysis of specific biological functions. In this article, we report an AND logic-gate-type fluorescent probe that can concurrently sense two biological events in living cells: H2 O2 accumulation and acidification. The probe exhibits a unique fluorescence sensing mechanism, in which a xanthene fluorophore is oxidatively transformed to a xanthone derivative by H2 O2 , thereby resulting in a clear dual-emission change. This transformation is significantly accelerated under weak acidic conditions, which enables the selective and sensitive detection of H2 O2 production in an acidic cellular compartment. This unique sensing property was successfully applied to the ratiometric fluorescence imaging of autolysosome formation in selective mitochondrial autophagy (mitophagy), which highlights the utility of this novel probe in autophagy research.

Design of ratiometric fluorescent probes based on arene-metal-ion interactions and their application to Cd(II) and hydrogen sulfide imaging in living cells.

Non-coordinative interactions between a metal ion and the aromatic ring of a fluorophore can act as a versatile sensing mechanism for the detection of metal ions with a large emission change of fluorophores. We report the design of fluorescent probes based on arene-metal-ion interactions and their biological applications. This study found that various probes having different fluorophores and metal binding units displayed significant emission redshift upon complexation with metal ions, such as Ag(I), Cd(II), Hg(II), and Pb(II). X-ray crystallography of the complexes confirmed that the metal ions were held in close proximity to the fluorophore to form an arene-metal-ion interaction. Electronic structure calculations based on TDDFT offered a theoretical basis for the sensing mechanism, thus showing that metal ions electrostatically modulate the energy levels of the molecular orbitals of the fluorophore. A fluorescent probe was successfully applied to the ratiometric detection of the uptake of Cd(II) ions and hydrogen sulfide (H2S) in living cells. These results highlight the utility of interactions between arene groups and metal ions in biological analyses.