The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

Objective To evaluate CTA characteristics of anomalous origin of coronary artery from the pulmonary artery (ACAPA).Methods The clinical data of 24 patients with ACAPA were retrospectively analyzed,and the results of CTA were compared with operation.Results In 24 ACAPA cases,20 cases (20/24,83.33％) occurred in the left coronary artery (LCA),1 case (1/24,4.17％) was in the right coronary artery (RCA),1 case (1/24,4.17％) was in the anterior descending artery (LAD) and 2 cases (2/24,8.33 ％) were in the circumflex artery (LCX).The origins of coronary anomalies originated from the posterior wall of the pulmonary sinus or pulmonary trunk in 11 cases (11/24,45.83 ％),left wall in 7 cases (7/24,29.17％),right wall in 4 cases (4/24,16.67％),originated in the left pulmonary artery in 2 cases (2/24,8.33％).Collateral circulation:Infant type was in 5 cases,no collateral vessels between the coronary artery was observed;adult type was in 19 cases,of which 16 cases were of abnormal origin of the LCA and RCA,1 case was of LAD,2 cases were of LCX.The double LAD and coronary arteries with an intramural segment were found in 1 case respectively.Surgery were performed in 19 cases.Five cases were reviewed by CTA,1 case with anastomotic stenosis of LCX,1 case with restenosis of right ventricular outflow tract and 1 case with coronary pseudoaneurysm.Conclusion CTA can clearly show the origin of abnormal coronary artery,the distance from the ascending aorta,collateral vessels,combined with other coronary artery malformations,which can help surgical preparation of preoperative surgical approach,and postoperative follow-up.