Role of Medaka (Oryzias latipes) Foxo3 in Resistance to Nervous Necrosis Virus Infection.

Upon encountering a virus, fish initiate an innate immune response, guided by IFNs. Foxo3 plays a part in the body's immune response; however, its specific role in the IFN-guided immune response in fish is yet to be clarified. In this study, we characterized foxo3 in Japanese medaka (Oryzias latipes) and examined its role in the IFN-dependent immune response upon infection with the RGNNV. The results show that the coding region of the medaka foxo3 gene is 2007 base pairs long, encoding 668 amino acids, and possesses a typical forkhead protein family structural domain. The product of this gene shares high homology with foxo3 in other fish species and is widely expressed, especially in the brain, eyes, testes, and heart. Upon RGNNV infection, foxo3-/- mutant larvae showed a lower mortality rate, and adults exhibited a significant reduction in virus replication. Moreover, the absence of foxo3 expression led to an increase in the expression of irf3, and a decrease in the expression of other IFN-related genes such as tbk1 and mapk9, implying that foxo3 may function as a negative regulator in the antiviral signaling pathway. These findings provide crucial insights for disease-resistant breeding in the aquaculture industry.

Arachidonic Acid Metabolites in Self-collected Biospecimens Following Campfire Exposure: Exploring Non-invasive Biomarkers of Wildfire Health Effects.

Climate change has contributed to increased frequency and intensity of wildfire. Studying its acute effects is limited due to unpredictable nature of wildfire occurrence, which necessitates readily deployable techniques to collect biospecimens. To identify biomarkers of wildfire's acute effects, we conducted this exploratory study in eight healthy campers (four men and four women) who self-collected nasal fluid, urine, saliva, and skin wipes at different time points before, during, and after 4-hour exposure to wood smoke in a camping event. Concentrations of black carbon in the air and polycyclic aromatic hydrocarbons in participants' silicone wristbands were significantly elevated during the exposure session. Among 30 arachidonic acid metabolites measured, lipoxygenase metabolites were more abundant in nasal fluid and saliva, whereas cyclooxygenase and non-enzymatic metabolites were more abundant in urine. We observed drastic increases, at 8 hours following the exposure, in urinary levels of PGE2 (398%) and 15-keto-PGF2α (191%) (FDR<10%), with greater increases in men (FDR < 0.01%) than in women. No significant changes were observed for other metabolites in urine or the other biospecimens. Our results suggest urinary PGE2 and 15-keto-PGF2α as promising biomarkers reflecting pathophysiologic (likely sex-dependent) changes induced by short-term exposure to wildfire.

Neighborhood-level socioeconomic disparities in Radon testing in North Carolina from 2010 to 2020.

Radon is a naturally occurring radioactive gas that poses significant health risks to humans, including increased risk of lung cancer. This study investigates the association of neighborhood-level socioeconomic variables with radon testing and radon exposure levels in North Carolina between 2010 and 2020. Our analysis of the two largest commercial household radon tests reveals that 67% of census tracts had testing rates below 10 tests per 1000 population, indicating low testing prevalence. Low radon levels (<2 pCi/L) were detected in 74.1% of the tracts (n = 1626), while medium levels of 2-4 pCi/L and ≥4 pCi/L were observed in 17.2% (n = 378) and 1.6% (n = 36) of the tracts. A generalized spatial regression model was employed to analyze the association between neighborhood-level socioeconomic variables and radon testing rates (per 1000 households), controlling for median radon testing results. The results show a positive correlation (P-value <0.001) of testing rate with various indicators of neighborhood affluence including education level, income, and occupation. In contrast, neighborhood disadvantage, including poverty, unemployment, and public assistance, was associated with a lower radon-testing rate (P-value <0.001). These findings highlight the need for targeted interventions to address socioeconomic disparities in radon testing and promote awareness and access to testing resources in lower socio-economic neighborhoods. Improving testing rates can effectively address radon-related health risks in North Carolina and across the U.S.

Aberrantly expressed HIF-1α enhances HCC stem cell-like traits via Wnt/ß-catenin signaling activation after insufficient radiofrequency ablation.

BACKGROUND: Radiofrequency ablation has become a favorable treatment modality for small hepatocellular carcinoma (HCC) recently; however, insufficient radiofrequency ablation (RFA) was shown to lead to enhanced invasiveness and metastasis of HCC in our previous study, while the underlying molecular mechanism has not been understood. MATERIALS AND METHODS: In order to explore the influence of the hypoxic microenvironment on residual cancer and cancer stem cell (CSC)-like characteristics of HCC cells in this process, an in vitro hypoxic model and an insufficient RFA mouse model were established with HCC cancer cell lines. Immunochemistry staining and western blot were used to examine the expression of hypoxia-inducible factor (HIF)-1α and liver CSC markers. The 3D colon formation assay, tumor cell invasion assay, and gene transfection assays were applied to test the change in liver CSC stemness and HCC cell invasion. RESULTS: After insufficient RFA treatment, the upregulated HIF-1α expression was associated with an increase in the CSC-like population in residual cancer. In vitro, hypoxic tumor cells showed aggressive CSC-like properties and phenotypes. Wnt/ß-catenin signaling activation was shown to be necessary for the acquisition of liver CSC-like characteristics under hypoxic conditions. CONCLUSION: Overall, the aberrantly enhanced HIF-1α expression enhanced the liver CSC-like traits via abnormal Wnt/ß-catenin signaling activation after insufficient RFA, and the overexpressed HIF-1α would be a vital factor and useful biomarker during the HCC recurrence and metastasis.

Carbohydrate-based drugs launched during 2000-2021.

Carbohydrates are fundamental molecules involved in nearly all aspects of lives, such as being involved in formating the genetic and energy materials, supporting the structure of organisms, constituting invasion and host defense systems, and forming antibiotics secondary metabolites. The naturally occurring carbohydrates and their derivatives have been extensively studied as therapeutic agents for the treatment of various diseases. During 2000 to 2021, totally 54 carbohydrate-based drugs which contain carbohydrate moities as the major structural units have been approved as drugs or diagnostic agents. Here we provide a comprehensive review on the chemical structures, activities, and clinical trial results of these carbohydrate-based drugs, which are categorized by their indications into antiviral drugs, antibacterial/antiparasitic drugs, anticancer drugs, antidiabetics drugs, cardiovascular drugs, nervous system drugs, and other agents.