1.Introduction and enlightenment of the Recommendations and Expert Consensus for Plasma and Platelet Transfusion Strategies in Critically Ill Children Following Severe Trauma, Traumatic Brain Injury, and/or Intracranial Hemorrhage: From the Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding
Zhenzhen JIANG ; Rong GUI ; Rong HUANG ; Junhua ZHANG ; Jiaohui ZENG ; Hao TANG ; Zhi LIN ; Dan WAN ; Mingyi ZHAO ; Minghua YANG ; Lan GU ; Haiting LIU
Chinese Journal of Blood Transfusion 2026;39(2):285-293
Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding developed a strategy for platelet and plasma infusion management in critically ill children based on systematic reviews and consensus meetings of international multidisciplinary experts. One good practice statement and six expert consensus statements were proposed for plasma and platelet transfusions in critically ill children following severe trauma, traumatic brain injury, and/or intracranial hemorrhage. This article introduces the specific methods and basis for the formation of recommendations in this part of the guide.
2.Construction and validation of circadian rhythm genes-related prognostic risk model for lung adenocarcinoma
Yanqi CUI ; Hu ZHAO ; Yawei ZHANG ; Lin NI ; Duohuang LIAN ; Jingrong YANG ; Shixin YE ; Fengfeng XU ; Jincan ZHANG ; Zhiyong ZENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(04):550-558
Objective To explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). Methods The Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. Gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients’ 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. Results Differentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. The scRNA-seq analysis showed that RORA and KLF10 were mainly expressed in natural killer cells. Conclusion The prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.
3.Application of Carbon Nanoparticle-Manganese Dioxide Injection in Gastrointestinal Staining-Based Marking and Localization in Rats and Pigs
Wanlin CHEN ; Qingrui DONG ; Mengtao LI ; Nan LIN ; Hu ZHAO ; Zaizhong ZHANG ; Lingjun ZENG ; Pei LI ; Jin YANG ; Yu WANG ; Aiwen HUANG
Laboratory Animal and Comparative Medicine 2026;46(5):727-739
ObjectiveTo develop a carbon nanoparticle-manganese dioxide (CN-MnO2) injection integrating visually identifiable staining and magnetic resonance (MR) T1/T2 dual-modal imaging, and to systematically evaluate its physicochemical properties, critical quality attributes, biocompatibility, and efficacy for gastrointestinal marking and localization. MethodsCN-MnO2 was prepared using a mild liquid-phase in situ redox deposition strategy and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The pH of CN-MnO2 was directly measured using a pH meter. The osmolality pressure of CN-MnO2 was determined by the freezing point depression method. The bacterial endotoxin was detected using the gel-clot Limulus amebocyte lysate test, which did not rely on absorbance readings. The appearance of the CN-MnO2 injection solution stored at 4 ℃ under light shielding and sealed for 0, 5, and 10 days was observed, and its hydrated particle size, polydispersity index, zeta potential, and pH were also measured. With gadopentetate dimeglumine (Gd-DTPA) as the positive control, different concentration gradients were established, and T1 and T2 relaxation times were measured to construct concentration-dependent plots of the longitudinal and transverse relaxation rates (R1 and R2) and calculate the corresponding relaxivities (r1 and r2), compare relaxivity performance, and determine the working concentration for subsequent in vivo experiments. Cytocompatibility was assessed using the methyl thiazolyl tetrazolium (MTT) assay and live/dead staining. Sixteen male 6-week-old SD rats were randomly assigned to an experimental group and a control group (n=8 per group) and subcutaneously injected with CN-MnO2 injection at a total Mn concentration of 0.80 mmol/L or an equal volume of normal saline, respectively. Short-term in vivo safety was evaluated by regular body weight monitoring, hematoxylin-eosin (HE) staining of major organs, hematological and serum biochemical analyses, inflammatory cytokine detection, and inductively coupled plasma optical emission spectrometry (ICP-OES) analysis. Eight male 5–6-month-old Bama minipigs were randomly assigned to a CN-MnO2 group (n=6) and a carbon nanoparticle suspension injection (CNSI) group (n=2). CN-MnO2 injection or CNSI was injected subserosally into the stomach, small intestine, and colon. Within 5 min after each injection, the maximum staining diameter at each injection site was measured and recorded. MR T1WI/T2WI scans were performed on days 3 and 7 after injection to evaluate MR visualization at the injection sites. At the end of observation, the injection sites and major organs were collected for histopathological evaluation by hematoxylin-eosin staining. ResultsCN-MnO2 appeared as a black suspension, with no obvious aggregation or sedimentation after standing at room temperature (20-25 ℃) for 15 days. Its average hydrodynamic diameter was approximately (228.7±15.3) nm, the polydispersity index was 0.184±0.021, and the zeta potential was (-24.6±2.8) mV. XPS showed that CN-MnO2 was mainly composed of C, O, and Mn, with oxygen accounting for approximately 68.82%. The Mn 2p spectrum exhibited two characteristic peaks at 642.4 and 653.1 eV. XRD indicated that low-crystallinity δ-MnO2 was dispersed within the carbon matrix. The pH was 6.82±0.06, the osmolality was (298.4±6.7) mOsm/kg, and the bacterial endotoxin level was below the detection limit. In vitro MR imaging showed a clear concentration-dependent response, with r1 and r2 values of 9.6 L·mmol-1·s-1 and 17.2 L·mmol-1·s-1, respectively, indicating favorable T1/T2 contrast performance superior to that of Gd-DTPA. At 0.80 mmol/L, CN-MnO2 showed no obvious cytotoxicity in vitro. Short-term safety evaluation in SD rats revealed no obvious inflammatory response, impairment of liver or renal function, or abnormal manganese accumulation in major organs. In Bama minipigs, the mean staining diameters of the CN-MnO2 group in the stomach, small intestine, and colon were (0.65±0.12) cm, (0.61±0.11) cm, and (0.58±0.10) cm, respectively, with no significant difference among the three injection sites (P>0.05). The overall mean staining diameter was smaller in the CN-MnO2 group than in the CNSI group (P<0.05). MR examinations showed that the injection sites were identifiable on both day 3 and day 7, with stronger signals observed on day 3. At the end of observation, no obvious pathological abnormalities were observed at the injection sites or in major organs. ConclusionA CN-MnO2 injection with uniform particle size and stable physicochemical properties can be successfully prepared. This formulation integrates visible gastrointestinal staining with MR T1/T2 dual-modal imaging, providing a new strategy for preoperative gastrointestinal marking and localization as well as precise intraoperative resection.
4.Latent tuberculosis infection among enterprise employees in Wenzhou City
ZENG Zhen ; ZHAO Lina ; SHAN Zhili ; MAO Jing ; LIN Hante ; MAO Lingqiong ; LI Jun
Journal of Preventive Medicine 2026;38(4):334-337
Objective:
To investigate the status and influencing factors of latent tuberculosis infection (LTBI) among enterprise employees in Wenzhou City, Zhejiang Province, so as to provide evidence for optimizing tuberculosis prevention and control strategies in enterprises.
Methods:
From August 2024 to September 2025, a convenience sampling method was used to select employees from 26 enterprises in Wenzhou City as the study participants. Demographic information, enterprise scale, and industry type were collected by reviewing enterprise employee management files. Interferon-gamma release assays were used to detect Mycobacterium tuberculosis infection and screen for LTBI. Factors affecting LTBI among enterprise employees were identified using a multivariable logistic regression model.
Results:
A total of 6 476 participants were surveyed, including 3 674 males (56.73%) and 2 802 females (43.27%). The median age was 37.00 (interquartile range, 20.00) years. A total of 994 cases of LTBI were detected, with a detection rate of 15.35%. Multivariable logistic regression analysis showed that male (OR=1.397, 95%CI: 1.211-1.612), age ≥45 years (45-<60 years, OR=1.919, 95%CI: 1.649-2.234; ≥60 years, OR=4.425, 95%CI: 3.170-6.177), household registration outside Zhejiang Province (OR=1.928, 95%CI: 1.577-2.357), employment in small or medium-sized enterprises (medium-sized, OR=1.663, 95%CI: 1.392-1.988; small-sized, OR=1.665, 95%CI: 1.358-2.040), and working in the manufacturing industry (OR=1.799, 95%CI: 1.147-2.822) were associated with a higher risk of LTBI among enterprise employees.
Conclusions
The detection rate of LTBI among enterprise employees in Wenzhou City was relatively low. Male employees, those aged ≥45 years, those with household registration outside Zhejiang Province, those working in small or medium-sized enterprises, and those in the manufacturing industry were identified as high-risk populations for LTBI.
5.Latent tuberculosis infection among HIV/AIDS cases in Wenzhou City
ZHAO Lina ; ZENG Zhen ; LIN Hante ; MAO Jing ; ZHU Tingting ; SHAN Zhili ; MAO Lingqiong ; LI Jun
Journal of Preventive Medicine 2026;38(6):550-554
Objective:
To investigate the status of latent tuberculosis infection (LTBI) and tuberculosis preventive treatment (TPT) among HIV/AIDS cases in Wenzhou City, Zhejiang Province, and to analyze the influencing factors of LTBI, so as to provide the evidence for optimizing active tuberculosis screening and early intervention strategies.
Methods:
Study subjects were HIV/AIDS cases who received antiretroviral therapy and CD4+T lymphocyte count testing at designated HIV treatment hospitals from October 2024 to August 2025. The interferon-gamma release assay was used for LTBI screening. Data on HIV/AIDS cases, including gender, age, and other variables, were collected through the Surveillance System of China Information System for Disease Control and Prevention. A multivariable logistic regression model was used to analyze the influencing factors for LTBI among HIV/AIDS cases.
Results:
A total of 3 719 HIV/AIDS cases were included, including 2 983 males (80.21%) and 736 females (19.79%). The study population was predominantly aged 40-<65 years, with 1 948 individuals accounting for 52.38%. LTBI was detected in 399 cases, with a detection rate of 10.73%. Among LTBI cases, 103 received TPT, representing a TPT rate of 25.81%. Multivariable logistic regression analysis showed that HIV/AIDS cases who were male (OR=1.796, 95%CI: 1.326-2.431), aged ≥40 years (40-<65 years, OR=1.895, 95%CI: 1.424-2.523; ≥65 years, OR=2.365, 95%CI: 1.575-3.551), non-Wenzhou household registration (OR=1.462, 95%CI: 1.150-1.857), with education level below junior college (primary school and below, OR=1.578, 95%CI: 1.023-2.394; junior high school, OR=1.725, 95%CI: 1.161-2.562; high school/technical secondary school, OR=1.639, 95%CI: 1.066-2.518), CD4+T lymphocyte count ≥500 cells/μL (OR=2.642, 95%CI: 1.420-4.915), and at the HIV infection stage (OR=1.322, 95%CI: 1.022-1.709) had a higher risk of LTBI.
Conclusions
The detection rate of LTBI and the TPT rate among LTBI cases are relatively low among HIV/AIDS cases in Wenzhou City. Gender, age, household registration, education level, CD4+T lymphocyte count, and disease stage are influencing factors for LTBI in HIV/AIDS cases.
6.Study on the effect and burden of precipitation on road traffic injuries in Zhejiang Province
Lihua GUO ; Weiquan ZENG ; Wenjun MA ; Ming ZHAO ; Jianxiong HU ; Na LI ; Jieming ZHONG ; Jingjing LIN
Chinese Journal of Epidemiology 2025;46(4):605-611
Objective:To analyze the effect of precipitation on road traffic injuries (RTI) in Zhejiang Province.Methods:The RTI surveillance and meteorological data from 2009 to 2022 in Zhejiang Province were collected. Based on the time-stratified case-crossover design, the precipitation of case day and control day was compared, and the distributed lag nonlinear model was applied to analyze the correlation of precipitation and RTI. Stratified analyses were conducted to analyze the effect modification of gender, age, injury location, and temperature. An attributable fraction was used to assess the burden of RTI caused by precipitation.Results:A total of 239 970 RTIs were monitored in Zhejiang Province from 2009 to 2022, averaging 46 daily cases. The distributed lag nonlinear model showed that compared with no rain, the risk of RTI increased first and then decreased with the increase of precipitation. The risk of RTI was the highest when the precipitation was 30.99 mm ( OR=1.08, 95% CI: 1.05-1.11). The adverse effects on RTI mainly occurred on the day of precipitation, and it showed insignificant or protective effects with the extension of lag days. 1.34%(95% CI: 1.31%-1.36%) of RTI could be attributed to precipitation. Stratified analysis showed that gender, age, injury location, and temperature may modify the effect of precipitation on RTI. Precipitation caused a heavier burden on RTI in subgroups aged 18-64, females, and occurring on roads and in low temperatures. Conclusions:Precipitation can increase the risk of RTI. People aged 18-64 or females are the key groups for RTI prevention, and prevention and control efforts of precipitation-related RTI should be increased in road and low-temperature environments.
7.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
8.Analysis of endovascular treatment for hepatic venous outflow obstruction after liver transplantation
Fuliang HE ; Jun WANG ; Yu WANG ; Xinyan ZHAO ; Fuquan LIU ; Lin WEI ; Wei QU ; Zhigui ZENG ; Liying SUN ; Zhijun ZHU
Chinese Journal of Hepatobiliary Surgery 2025;31(7):492-496
Objective:To analyze the efficacy of endovascular treatment for venous outflow tract obstruction after liver transplantation.Methods:A retrospective analysis was conducted on the data of 7 patients with venous outflow tract obstruction after liver transplantation admitted to Beijing Friendship Hospital, Capital Medical University from November 2020 to December 2024. Among them, there were 5 males and 2 females, with the age of (22.3±8.1) years. The primary diseases included 2 cases of Budd-Chiari syndrome, 1 case of hepatic veno-occlusive disease, 1 case of portal veno-hepatic sinus vascular disease, 1 case of ornithine carbamoyltransferase deficiency, 1 case of primary biliary cirrhosis, and 1 case of autoimmune cirrhosis. Analyze the patient's clinical manifestations, obstruction of venous outflow tract, hemoglobin levels within one week before and one week after the operation, endovascular treatment conditions, and intraoperative complications such as abdominal hemorrhage and vascular injury. Ultrasound was used to measure the depth of ascites and pleural effusion. All patients were followed up immediately after the operation through phone calls or follow-up visits. The clinical symptoms, abdominal vascular ultrasound, enhanced CT and survival status of the patients were followed up.Results:All 7 patients were diagnosed with venous outflow tract obstruction by intraoperative angiography, including 1 cases of inferior vena cava obstruction, 2 cases of hepatic vein obstruction, and 4 cases of vena cava combined with hepatic vein obstruction. A total of 12 endovascular treatments were performed on 7 patients. Among them, 4 patients received balloon dilation and angioplasty once, 1 patient received balloon dilation and angioplasty twice, 1 patient underwent hepatic vein stent implantation after 2 hepatic vein balloon dilation and angioplasty, and 1 patient underwent intrahepatic portosystemic shunt via jugular vein after 2 hepatic vein balloon dilation and angioplasty. The abdominal distensionof the patients were all relieved after the operation, the ascites and pleural effusion decreased, and the edema symptoms of the lower extremities disappeared. There were no intraoperative complications. The preoperative hemoglobin of 7 patients was (113.4±34.0) g/L, and the postoperative hemoglobin was (126.6±34.8) g/L, which increased significantly compared with that before the operation, and the difference was statistically significant ( t=-0.71, P=0.038). Seven patients were followed up for 6 to 24 months, with a median of 12 months. None of them had obvious symptoms including abdominal distension. Abdominal ultrasound and CT indicated that the blood flow of the transplanted liver was unobstructed, and no patient died. Conclusion:Venous outflow tract obstruction after liver transplantation can cause severe symptoms. Endovascular treatment is an effective treatment for venous outflow tract obstruction after liver transplantation.
9.Fast Screening of 10 Kinds of Illegal Aphrodisiac Drugs in Foods by Matrix-assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry
Xi ZENG ; Yu WANG ; Ying-Li CHEN ; Tian-Tian ZHAO ; Zhen-Lin XU ; Heng-Xin ZHOU
Chinese Journal of Analytical Chemistry 2025;53(3):441-450,中插3-中插5
A matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS)method was developed for simultaneous analysis of 10 kinds of aphrodisiac drugs,including sildenafil,acetildenafil,nor-acetildenafil,homosildenafil,lodenafil carbonate,sildlenafil dimer impurity,vardenafil dimer,hydroxyacetildenafil,N-desmethylsildenafil and udenafil.By using different matrices(α-cyano-4-hydroxycinnamic acid(HCCA)and sinapic acid(SA)),the effects of solvents,amount of matrices,laser intensity and spotting methods on the peak strength and signal intensity of MALDI-TOF MS for the aphrodisiac drugs were investigated.As a result,SA was chosen as the matrix,and then dispersed in methanol-water(50∶50,V/V),and spotted by matrix firstly and sample secondly approach with the reflect linear positive mode and laser power of 60%.Under optimal conditions,the proposed MALDI-TOF MS method could obtain stable signal,high intensity and well-repeated mass spectrometric results.The results of method validation showed a linear range from 10 to 100 ng/mL,and the regression coefficients(r)were all above 0.985.The limits of detection(LOD)were 0.1-1.0 ng/mL,and the recoveries were in the range of 72.9%-109.9%for health wine,soft capsule and instant coffee samples,while the relative standard deviations(RSDs)ranged from 0.7%to 11.3%(n=3).The test results of 10 kinds of aphrodisiac drugs by MALDI-TOF MS were in accordance with the results of high-performance liquid chromatography-tandem mass spectrometry.This method exhibited high sensitivity,high accuracy,good anti-interference ability,low chemical solvents consumption and environmentally friendliness,and could be used to detect drugs without standards.The developed MALDI-TOF MS method could realize the non-target screening and detection of 10 kinds of illegally added aphrodisiac drugs in foods.
10.Discovery of a novel AhR-CYP1A1 axis activator for mitigating inflammatory diseases using an in situ functional imaging assay.
Feng ZHANG ; Bei ZHAO ; Yufan FAN ; Lanhui QIN ; Jinhui SHI ; Lin CHEN ; Leizhi XU ; Xudong JIN ; Mengru SUN ; Hongping DENG ; Hairong ZENG ; Zhangping XIAO ; Xin YANG ; Guangbo GE
Acta Pharmaceutica Sinica B 2025;15(1):508-525
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.


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