Background: The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates the expression of xenobiotic detoxification genes and is a critical mediator of gene–environment interactions. Many AHR target genes identified by genome-wide gene expression profiling have morphogenetic functions, suggesting that AHR may play a role in embryonic development.Objectives: To characterize the developmental functions of the AHR, we studied the consequences of AHR activation by the agonist 2,3,7,8-tetrachlorodibenzo-p-doxin (TCDD), and the result of its repression by the antagonists 6,2,4-trimethoxyflavone and CH 223191 or by short-hairpin RNA (shRNA)-mediated Ahr knockdown during spontaneous differentiation of embryonic stem (ES) cells into cardiomyocytes.Methods: We generated an AHR-positive cardiomyocyte lineage differentiated from mouse ES cells that expresses puromycin resistance and enhanced green fluorescent protein (eGFP) under the control of the Cyp1a1 (cytochrome P450 1a1) promoter. We used RNA sequencing (RNA.Seq) to analyze temporal trajectories of TCDD-dependent global gene expression in these cells during differentiation.Results: Activation, inhibition, and knockdown of Ahr significantly inhibited the formation of contractile cardiomyocyte nodes. Global expression analysis of AHR-positive cells showed that activation of the AHR/TCDD axis disrupted the concerted expression of genes that regulate multiple signaling pathways involved in cardiac and neural morphogenesis and differentiation, including dozens of genes encoding homeobox transcription factors and Polycomb and trithorax group proteins.Conclusions: Disruption of AHR expression levels resulted in gene expression changes that perturbed cardiomyocyte differentiation. The main function of the AHR during development appears to be the coordination of a complex regulatory network responsible for attainment and maintenance of cardiovascular homeostasis.Citation: Wang Q, Chen J, Ko CI, Fan Y, Carreira V, Chen Y, Xia Y, Medvedovic M, Puga A. 2013. Disruption of aryl hydrocarbon receptor homeostatic levels during embryonic stem cell differentiation alters expression of homeobox transcription factors that control cardiomyogenesis. Environ Health Perspect 121:1334–1343; http://dx.doi.org/10.1289/ehp.1307297
Environmental contamination caused by COVID-19 patients could be a medium of transmission. Previous reports of SARS-CoV-2 in environmental surfaces were about short-term contamination. This study investigated SARS-CoV-2 RNA existence in room-temperature and low-temperature environments long after exposure (>28 days). A department store, where a COVID-19 outbreak was occurred in January 2020 (the epicenter of 43 COVID-19 patients), and a patient's apartment were included as room-temperature environments after being blocked for 57 days and 48 days, respectively. Seven cold storages and imported frozen foods inside were included as low-temperature environments (under −18 °C). Twenty food markets with potential contamination of imported frozen foods were also included to study the consecutive contamination. Information about temperature, relative humidity, and the number of days of environmental samples since the last exposure was collected and analyzed. In sum, 11,808 swab samples were collected before disinfection, of which 35 samples were positive. Persistent contamination of SARS-CoV-2 RNA was identified in the apartment (6/19), the department store (3/50), food packages in cold storages (23/1360), environmental surfaces of cold storages (2/345), and a package in the food market (1/10,034). Two positive samples were isolated from the bathroom of the apartment (66.7 %, 2/3), and doorknobs were proved with contamination in the apartment (40 %, 2/5) and cold storage (33.3 %, 1/3). The epidemiology information and environmental contamination results of an imported frozen food related COVID-19 case (138th COVID-19 patient in Tianjin) were analyzed. Based on the Ct values, the number of copies of two target genes was calculated by standard curves and linear regressions. In conclusion, SARS-CoV-2 RNA can be detected in room-temperature environments at least 57 days after the last exposure, much longer than previous reports. Based on the results of this study and previous studies, infectious SARS-CoV-2 could exist for at least 60 days on the surface of cold-chain food packages. Doorknobs and toilets (bathrooms) were important positions in COVID-19 control. High-risk populations of cold-chain-related logistic operations, such as porters, require strict prevention and high-level personal protection.
Hepatocellular carcinoma (HCC) is a type of cancer that has high rates of recurrence and mortality. One of the most important factors that lead to treatment failure of HCC is the acquisition of multidrug resistance (MDR). Development of specific ligands for multidrug-resistant HCC will provide useful molecular tools for precise diagnosis and targeted theranostics. Herein, a multidrug-resistant HCC cell (HepG2/MDR)-specific aptamer was developed through Cell-SELEX (systematic evolution of ligands by exponential enrichment) technology. With dissociation constants lying in the nanomolar range, the molecularly designed PS-ZL-7c aptamer showed great selectivity to drug-resistant cancer cells. The in vivo imaging results illustrated that the PS-ZL-7c specifically accumulated in the drug-resistant tumors but not in drug-sensitive tumors and normal tissues, indicating that the PS-ZL-7c aptamer possessed excellent potential as a targeting ligand for precise diagnosis and target theranostics of multidrug-resistant HCC.
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