Benz[a]anthracene (BaA), a hazardous polycyclic aromatic hydrocarbon classified by the EPA, is a probable reproductive toxicant. Epidemiological studies suggest that BaA exposure may be a risk factor for recurrent miscarriage (RM). However, the underlying mechanisms are not well understood. This study identified DEC1 as a key gene through RNA-seq and single-cell RNA sequencing analysis. DEC1 expression was found to be downregulated in villous tissues from women with RM and in primary extravillous trophoblasts (EVTs) exposed to BaA. BaA suppressed DEC1 expression by promoting abnormal methylation patterns. Further analysis revealed that ARHGAP5 is a direct target of DEC1 in EVTs, where DEC1 inhibits trophoblast invasion by directly regulating ARHGAP5 transcription. Additionally, BaA destabilized matrix metalloproteinase 2 (MMP2) by activating the aryl hydrocarbon receptor (AhR) and promoting E3 ubiquitin ligase MID1-mediated degradation. In a mouse model, BaA induced miscarriage by modulating the DEC1/ARHGAP5 and MID1/MMP2 axes. Notably, BaA-induced miscarriage in mice was prevented by DEC1 overexpression or MID1 knockdown. These findings indicate that BaA exposure leads to miscarriage by suppressing the DEC1/ARHGAP5 pathway and enhancing the MID1/MMP2 pathway in human EVTs.
Currently, organic artificial enzymes as biocatalysts have been extensively used to construct various colorimetric sensors. However, exploiting a potential organic artificial enzyme with high catalytic efficiency still remains a challenge. To address this issue, herein, we synthesize an acridone derivative 10-benzyl-2-amino-acridone (BAA). The synthesized BAA exhibits an intrinsic visible-light-stimulated oxidase-like activity, which is capable of oxidizing various chromogenic substrates without destructive hydrogen peroxide (H 2 O 2 ) under visible light stimulation , resulting in colored products. The reaction system can be regulated by switching light on and off, which is milder and more reliable means than others H 2 O 2 -dependent. The photocatalytic mechanism of BAA is investigated in detail. However, l -ascorbic acid (AA), an antioxidant generating from the acid phosphatase (ACP)-mediated hydrolysis of 2-phospho- l -ascorbic acid (AAP), is able to inhibit the catalytic activity of BAA. Based on the above properties, a facile, photo-switchable and low-cost colorimetric sensing strategy is developed for ACP detection. The linear range is 0.05–2.5 U/L (r = 0.9994), and the limit of detection (LOD) is 0.0415 U/L. Moreover, the proposed sensing system can be applied for monitoring ACP activity in practical samples, demonstrating promising applications in clinical analysis and biosensor platform.
A biosensing system is established for the multi-amplified detection of DNA or specific substrates of aptamers under isothermal conditions , which combines nicked rolling circle amplification (N-RCA) and beacon assisted amplification (BAA) with sensitive colorimetric technique by using DNAzymes as reporter units. According to the configuration, the analysis of DNA is accomplished by recognizing the target to capture nucleic acid-functionalized magnetic particles, followed by the self-assembly of the other two nucleic acids into multicomponent DNA supramolecular structure on magnetic particles. After magnetic separation, the circularization with ligase and the fragmentation with polymerase activate N-RCA and BAA in the presence of polymerase, dNTPs , and the nicking endonuclease , successively producing horseradish peroxidase (HRP)-mimicking DNAzymes that act as colorimetric reporter to catalyze the oxidation of ABTS 2− by H 2 O 2 in the presence of hemin . Under the optimized conditions, we obtain a wide dynamic range for DNA analysis over 6 orders of magnitude from 1.0×10 −14 to 1.0×10 −9 M with a low limit of detection of 6.8×10 −15 M. In the absence of a target, neither self-assembly of nucleic acids nor amplification process can be initiated, indicating an excellent selectivity of the proposed strategy. Similarly, an analogous system is activated by cancer cells or lysozyme through cooperative self-assembly of nucleic acids on magnetic particles in the presence of respective substrates of aptamers to synthesize HRP-mimicking DNAzymes that give the readout signal for the recognition events, achieving LODs of 81 Ramos cells and 7.2×10 −15 M lysozyme, respectively.
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