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FAM129B, an antioxidative protein, reduces chemosensitivity by competing with Nrf2 for Keap1 binding.
BackgroundThe transcription factor Nrf2 is a master regulator of antioxidant response. While Nrf2 activation may counter increasing oxidative stress in aging, its activation in cancer can promote cancer progression and metastasis, and confer resistance to chemotherapy and radiotherapy. Thus, Nrf2 has been considered as a key pharmacological target. Unfortunately, there are no specific Nrf2 inhibitors for therapeutic application. Moreover, high Nrf2 activity in many tumors without Keap1 or Nrf2 mutations suggests that alternative mechanisms of Nrf2 regulation exist.MethodsInteraction of FAM129B with Keap1 is demonstrated by immunofluorescence, colocalization, co-immunoprecipitation and mammalian two-hybrid assay. Antioxidative function of FAM129B is analyzed by measuring ROS levels with DCF/flow cytometry, Nrf2 activation using luciferase reporter assay and determination of downstream gene expression by qPCR and wester blotting. Impact of FAM129B on in vivo chemosensitivity is examined in mice bearing breast and colon cancer xenografts. The clinical relevance of FAM129B is assessed by qPCR in breast cancer samples and data mining of publicly available databases.FindingsWe have demonstrated that FAM129B in cancer promotes Nrf2 activity by reducing its ubiquitination through competition with Nrf2 for Keap1 binding via its DLG and ETGE motifs. In addition, FAM129B reduces chemosensitivity by augmenting Nrf2 antioxidative signaling and confers poor prognosis in breast and lung cancer.InterpretationThese findings demonstrate the important role of FAM129B in Nrf2 activation and antioxidative response, and identify FMA129B as a potential therapeutic target. FUND: The Chang Gung Medical Foundation (Taiwan) and the Ministry of Science and Technology (Taiwan)
Vertical Integration in the Taiwan Aquaculture Industry
The study aims to improve the distribution channels in the Taiwan aquaculture industry through a better vertical integration. This study is derived from a need to improve the distribution performance of agricultural-based industries in response to increasing food demands in Asia and elsewhere. Based on a four-by-eight matrix derived from both a value chain and a service profit chain, thirty different strategies are developed. This development is based on key success factors and strategies for vertical integration interviewed and cited in the literatures. The findings are identified by applying the Gray Relational Analysis (GRA). For this study, the key success factors for aquaculture wholesale markets include the communication, integration and cohesion of opinion within the wholesale market; government support; andmutual trust between members of the vertical integration scheme. The suitable vertical integration strategies are an improved safety and hygiene inspection of aquaculture products, accuracy of aquaculture product categorization, and precision in product weighing.aquaculture industry, grey relational analysis (GRA), channels integration
The Assessment for Sensitivity of a NO2 Gas Sensor with ZnGa2O4/ZnO Core-Shell Nanowires—a Novel Approach
The application of novel core-shell nanowires composed of ZnGa2O4/ZnO to improve the sensitivity of NO2 gas sensors is demonstrated in this study. The growth of ZnGa2O4/ZnO core-shell nanowires is performed by reactive evaporation on patterned ZnO:Ga/SiO2/Si templates at 600 °C. This is to form the homogeneous structure of the sensors investigated in this report to assess their sensitivity in terms of NO2 detection. These novel NO2 gas sensors were evaluated at working temperatures of 25 °C and at 250 °C, respectively. The result reveals the ZnGa2O4/ZnO core-shell nanowires present a good linear relationship (R2 > 0.99) between sensitivity and NO2 concentration at both working temperatures. These core-shell nanowire sensors also possess the highest response (<90 s) and recovery (<120 s) values with greater repeatability seen for NO2 sensors at room temperature, unlike traditional sensors that only work effectively at much higher temperatures. The data in this study indicates the newly-developed ZnGa2O4/ZnO core-shell nanowire based sensors are highly promising for industrial applications
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