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A molecular design strategy to construct the near-infrared fluorescent probe for selectively sensing human cytochrome P450 2J2
摘要: Cytochrome P450 2J2 (CYP2J2), a key enzyme responsible for oxidative metabolism of various xenobiotics and endogenous compounds, participates in a diverse array of physiological and pathological processes in humans. Its biological role in tumorigenesis and cancer diagnosis remains poorly understood, owing to the lack of molecular tools suitable for real-time monitoring CYP2J2 in complex biological systems. Using molecular design principles we were able to modify the distance between the catalytic unit and metabolic recognition moiety, allowing us to develop a CYP2J2 selective fluorescent probe using a near-infrared fluorophore (E)-2-(2-(6-hydroxy-2, 3-dihydro-1H-xanthen-4-yl)vinyl)-3,3-dimethyl-1-propyl-3H-indol-1-ium iodide (HXPI). To improve the reactivity and isoform specificity, a self-immolative linker was introduced to the HXPI derivatives in order to better fit the narrow substrate channel of CYP2J2, the modification effectively shortened the spatial distance between the metabolic moiety (O-alkyl group) and catalytic center of CYP2J2. After screening a panel of O-alkylated HXPI derivatives, BnXPI displayed the best combination of specificity, sensitivity and applicability for detecting CYP2J2 in vitro and in vivo. Upon O-demethylation by CYP2J2, a self-immolative reaction occurred spontaneously via 1,6-elimination of p-hydroxybenzyl resulting in the release of HXPI. Allowing BnXPI to be successfully used to monitor CYP2J2 activity in real-time for various living systems including cells, tumor tissues, and tumor-bearing animals. In summary, our practical strategy could help the development of a highly specific and broadly applicable tool for monitoring CYP2J2, which offers great promise for exploring the biological functions of CYP2J2 in tumorigenesis.
关键词: Cytochrome P450 2J2,near-infrared fluorescent probe,real-time monitoring,molecular design,CYP2J2,tumorigenesis
更新于2025-09-04 15:30:14
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Real-time determination of enantiomeric and isomeric content using photoelectron elliptical dichroism
摘要: The fast and accurate analysis of chiral chemical mixtures is crucial for many applications but remains challenging. Here we use elliptically-polarized femtosecond laser pulses at high repetition rates to photoionize chiral molecules. The 3D photoelectron angular distribution produced provides molecular fingerprints, showing a strong forward-backward asymmetry which depends sensitively on the molecular structure and degree of ellipticity. Continuously scanning the laser ellipticity and analyzing the evolution of the rich, multi-dimensional molecular signatures allows us to observe real-time changes in the chemical and chiral content present with unprecedented speed and accuracy. We measure the enantiomeric excess of a compound with an accuracy of 0.4% in 10 min acquisition time, and follow the evolution of a mixture with an accuracy of 5% with a temporal resolution of 3 s. This method is even able to distinguish isomers, which cannot be easily distinguished by mass-spectrometry.
关键词: real-time monitoring,isomer distinction,photoelectron elliptical dichroism,enantiomeric excess,chiral molecules
更新于2025-09-04 15:30:14
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Comprehensive Remote Sensing || Land Surface Phenology: Climate Data Record and Real-Time Monitoring
摘要: Vegetation phenology is the expression of the seasonal cycles of plant processes and their connections to climate changes. Shifts in phenology reflect the change in global temperature and precipitation, land cover properties, and land use activities (Schwartz and Reed, 1999; de Beurs and Henebry, 2004; Lambin et al., 2003). As a result, phenology is one of the most effective and sensitive indicators for monitoring environmental changes. Long-term records of vegetation phenology have great contributions to understanding regional and global ecosystems and climate changes. This is evident from field phenological records that reflect local and regional increase in air temperature due to anthropogenic greenhouse effects during the last few decades (Parmesan and Yohe, 2003).
关键词: Climate Data Record,Real-Time Monitoring,Vegetation Phenology,Satellite Data,Land Surface Phenology
更新于2025-09-04 15:30:14