Advancing the predictivity of skin sensitization by applying a novel HMOX1 reporter system.

Reporter cell lines are a particularly useful tool to screen for the skin sensitization potential of chemicals. Current cell models based on Keap1-Nrf2 mimic induction by conducting antioxidant response element-luciferase plasmids. However, plasmid-based reporters may ignore comprehensive aspects of induction, thus affecting the accuracy of hazard identification. Herein, we developed a novel HaCaT-based reporter system, EndoSens, whereby luciferase was specifically inserted into the cassette for heme oxygenase (decycling) 1 (HMOX1, the most consistent marker induced by skin sensitizers) by CRISPR/Cas9. Testing data from 20 coded substances showed an accuracy of 90%, sensitivity of 91.7%, and specificity of 87.5%, which exceeded the OECD requirement. Among the 35 chemicals examined, predictivity was better than reported for the validated KeratinoSens™. These results indicate that the EndoSens assay could advance the predictivity of skin sensitization, thus making it a promising tool for in vitro skin sensitization testing.

Tracing the sources and evaporation fate of surface water and groundwater using stable isotopes of hydrogen and oxygen.

Recognizing the origins and movement processes of surface water and groundwater is crucial for understanding hydrochemical genesis, conserving water supplies, and managing water resources. Estimating the source water typically involves identifying the intersection of evaporation line (EL) and meteoric water line. However, there is currently confusion in determining the regional EL and selecting strategies for estimating the source water. This study aimed to explore the source of surface water and groundwater, as well as evaporation effect utilizing stable isotope tracing (δ2H and δ18O). The line-conditioned excess was adopted to differentiate evaporated water and non-evaporated water, then Craig-Gordon model and an analytical framework with Bayesian theory were used to investigate the source of surface water and groundwater and the evaporation influence. The findings revealed that surface water and groundwater in the northern region of the Weihe River suffered more sever evaporation impacts that the south, and the evaporated surface water (7.54 % to 27.34 %) with a wider range of mean evaporation ratio than evaporated groundwater (5.38 % to 8.52 %). Monsoon precipitation is the main contributor to both surface water (contribution ratio: 0.46) and groundwater (0.49) sources. This research provides specific information on evaporation and detailed insights into the source water of surface water and groundwater, aiding in understanding the evaporation effect during the hydrological cycle and facilitating the management of regional water resources.

Rspo1 inhibited apoptosis of glucocorticoid-induced osteoblasts via Wnt/ß-catenin pathway in Legg-Calve-Perthes disease.

BACKGROUND: The pathogenesis of Legg-Calve-Perthes disease (LCPD), a juvenile form of avascular necrosis of the femoral head (ANFH), is not fully understood. OBJECTIVES: The purpose of this work was to study the regulatory effect of R-spondin 1 (Rspo1) on osteoblastic apoptosis and evaluate the pre-clinical efficacy of recombinant human protein Rspo1 (rhRspo1) in treatment of LCPD. MATERIAL AND METHODS: This is an experimental study. In vivo rabbit ANFH model was established. Human osteoblast cell line hFOB1.19 (hFOB) was used to overexpress and silence Rspo1 in vitro. Additionally, hFOB cells were induced with glucocorticoid (GC) and methylprednisolone (MP), and treated with rhRspo1. The expressions of Rspo1, ß-catenin, Dkk-1, Bcl-2, and caspase-3, and the apoptosis rate of hFOB cells were examined. RESULTS: The expressions of Rspo1 and ß-catenin were lower in ANFH rabbits. The expression of Rspo1 was decreased in GC-induced hFOB cells. Compared to the control group, after 1 µM MP induction for 72 h, the expressions of ß-catenin and Bcl-2 were higher, while Dkk-1, caspase-3 and cleaved caspase-3 expressions were lower in Rspo1 overexpression and rhRspo1-treated groups. The apoptosis rate of GC-induced hFOB cells was decreased in Rspo1 overexpression and rhRspo1-treated groups compared to the control group. CONCLUSIONS: R-spondin 1 inhibited GC-induced osteoblast apoptosis via Wnt/ß-catenin pathway, which might be associated with the development of ANFH. Moreover, rhRspo1 had a potential pre-clinical therapeutic effect on LCPD.

Groundwater contamination risk assessment using a modified DRATICL model and pollution loading: A case study in the Guanzhong Basin of China.

Groundwater contamination risk assessment is not only the basis for groundwater management, but also an effective tool for groundwater pollution control and prevention. However, only groundwater vulnerability assessment is not enough to prove the risk of groundwater contamination. Therefore, this study describes an evaluation method combining aquifer intrinsic vulnerability and pollution source loading to evaluate groundwater contamination risk in Guanzhong Basin on a macro scale. A modified DRATICL model was introduced to evaluate the intrinsic vulnerability, and the analytic hierarchy process (AHP) and the entropy weight method were combined to determine the weight of each evaluation factor. Pollution loading was evaluated by quantifying the characteristics of potential pollution sources, mainly including pollutant toxicity, pollutant release possibility and potential pollutant release amount. Finally, total iron, Cl-, SO42-, F-, COD (Chemical Oxygen Demand), NO3-, NO2- and TDS (Total Dissolved Solids) are used to calculate the water quality index and verify the model results. The results showed that industries were the most harmful potential pollution sources in the study area, followed by landfills. Very high vulnerability areas were mainly situated around Huazhou District, Huayin and Dali County, as well as the low terraces around Zhouzhi County and Hu County, which are mainly caused by shallow groundwater depth and high net recharge. The final groundwater contamination risk results showed the high groundwater contamination risks are detected around Xi'an City, Xianyang City, Hancheng City and Dali County. Both high vulnerability and high pollution loading were present at the Jingwei District in the north of Xi'an City, where a priority attention should be given.