Spatiotemporal distribution of ecological risk of antibiotics in seven major river basins of China: An optimized multilevel assessment approach.

Antibiotics have been recognized as emerging pollutants due to their ecological and human health risks. This paper aims to enhance the ecological risk assessment (ERA) framework for antibiotics, to illustrate the distribution of these risks across different locations and seasons, and to identify the antibiotics that pose high ecological risk. This paper focuses on 52 antibiotics in seven major basins of China. Relying on the optimized approach of ERA and antibiotic monitoring data published from 2017 to 2021, the results of ERA are presented in multilevel. Across the study area, there are marked variations in the spatial distribution of antibiotics' ecological risks. The Huaihe River Basin, the Haihe River Basin, and the Liaohe River Basin are the top three in the ranking of present ecological risks. The research results also reveal significant differences in temporal variation, underscoring the need for increased attention during certain seasons. Ten antibiotics with high contribution rates to ecological risk are identified, which is an important reference to formulate an antibiotic control list. The multilevel results provided both risk values and their ubiquities across a broad study region, which is a powerful support for developing ecological risk management of antibiotics.

Ethiadin Induces Apoptosis and Suppresses Growth of MCF-7 Breast Cancer Cells by Regulating the Phosphorylation of Glycogen Synthase Kinase 3 Beta (GSK3beta).

Glycogen synthase kinase 3 beta (GSK3ß) has emerged as a therapeutic target for breast cancer. As inhibitors of GSK-3ß, 1,2,4-thiadiazole-3,5-dione (TDZD) family members have been reported as potential candidates for cancer treatment. In this study, the anticancer effects of ethiadin (ETD-174), one of the chemical synthesis compounds of TDZD, were investigated in MCF-7 human breast cancer cells. MCF-7 cells incubated with different doses of ETD-174 for different time periods. CCK-8 assays were carried out to test the effect of ETD-174 on the proliferation of MCF-7 cells. The occurrence of apoptosis was detected by Hoechst 33258 staining and flow cytometry. ETD-174 on cell migration and colony formation were examined by wound healing experiments and soft agar assays. Relative protein expressions were conducted with immunoblot assay. ETD-174 demonstrated a higher degree of cytotoxicity in MCF-7 cells. Topical morphological changes of apoptotic body formation after ETD-174 treatment were observed. Meanwhile, apoptosis was elicited by ETD-174. Also, ETD-174 could inhibit the migration and clonality of MCF-7 cells. After the treatment with ETD-174, the level of phosphorylation of GSK3ßSer9 in MCF-7 cells increased significantly, and the enzymatic activity of GSK3ß decreased. ETD-174 is likely to have an effective suppressor role in breast cancer, suggesting that pharmacological inhibition of GSK3ß as a novel treatment modality for breast cancer should warrant further investigation.

Ciliary localization of folliculin mediated via a kinesin-2-binding motif is required for its functions in mTOR regulation and tumor suppression.

Folliculin (FLCN) is a tumor suppressor protein involved in many cellular processes, including cell signaling, apoptosis, and autophagy. In ciliated cells, FLCN localizes to primary cilia and controls mTORC1 signaling in response to flow stress. Here, we show that the ciliary localization of FLCN requires its interaction with kinesin-2, the motor protein for anterograde intraflagellar transport. FLCN binds to kinesin-2 through a loop region in the middle of the protein. Single point mutations within this region of FLCN disrupt its kinesin-2 binding and ciliary entry. The mutants lose the ability to suppress the abnormal mTORC1/2 signaling activities and anchorage-independent growth of FLCN-deficient tumor cells. These observations suggest that ciliary localization of FLCN is essential for its function as a tumor suppressor.