Beta-catenin knockdown impairs the viability of ovarian cancer cells by modulating YAP-dependent glycolysis.

OBJECTIVES: Ovarian cancer (OC) ranks fifth among the main causes of cancer-related deaths in women worldwide. PCLAF/KIAA0101 and Yes-associated protein (YAP) have been linked to several human malignant cancers, including OC. However, the roles of KIAA0101 and YAP in glycolysis-dependent OC cell proliferation remain unknown. METHODS: qRT-PCR and western blot were performed to analyze the KIAA0101 expression. Short hairpin RNA transfection was performed to silence KIAA0101 expression in cells. Cell viability and apoptosis were assayed by colony formation and flow cytometry, respectively. Glucose uptake, lactate production, and glycolytic enzyme expression were assessed to determine the level of cellular glycolysis. Phosphorylation and the nuclear localization of YAP were assessed to determine YAP activation. RESULTS: OC tissue and cell lines exhibited higher KIAA0101 expression than the non-cancerous tissues and cells. KIAA0101 silencing reduced the proliferation and increased the apoptosis of both A2780 and ES-2 OC cell lines. Furthermore, KIAA0101 depletion suppressed glycolysis and YAP activation, as evidenced by increased YAP phosphorylation and decreased nuclear localization. Reactivation of YAP was performed by administration of mitochonic acid 5 in both OC cell lines with KIAA0101 knockdown. Glucose uptake, lactate production, phosphofructokinase, pyruvate dehydrogenase beta, pyruvate kinase M2, triosephosphate isomerase 1, glucose-6-phosphate dehydrogenase, enolase 1, and lactate dehydrogenase expression levels in cells recovered after the reactivation of YAP. Additionally, YAP reactivation increased cell proliferation and inhibited apoptosis. CONCLUSIONS: This study showed that KIAA0101 could promote glycolysis during nasopharyngeal carcinoma development through YAP signaling activation, suggesting that KIAA0101 could serve as a target for OC treatment.

Research on sustainable development evaluation and improvement path of resource-based cities based on coupling of emergy and system dynamics.

The evaluation of the sustainable development of resource-based cities is still one of the hotspots in today's social research. Taking Jining, Shandong Province, as the research object, this work combines a relevant emergy evaluation index system with system dynamics, establishes a resource-based city emergy flow system dynamics model, and studies sustainable development path in the next planning year. In the work, the key factors affecting the sustainable development of Jining are obtained through the coupling of regression and SD sensitivity analysis, and some scenarios are set up by combining them with the local 14th Five-year plan. Besides, the appropriate scenario (M-L-H-H) for Jining's future sustainable development is chosen in accordance with regional circumstances. That is, during the 14th Five-year Plan period, the appropriate development ranges for the growth rate of social fixed assets investment, the growth rate of raw coal emergy, the growth rate of grain emergy and the reduction rate of solid waste emergy are 17.5-18.3%, - 4.0 to - 3.2%, 1.8-2.6% and 4-4.8%. The methodology system constructed in this article can serve as a reference for similar studies, and the research findings can aid the government in formulating pertinent plans for resource-based cities.

Evaluation of regional sustainability through emergy analysis: a case study of nine cities in the Yellow River Basin of China.

The Yellow River is an important ecological shelter zone and economic belt in China. However, rapid urbanization and industrialization has produced a fragile ecological environment conditions and unbalanced economic development in the Yellow River Basin (YRB). Ecological protection and high-quality development of the YRB has been China's national strategy since 2019. As the only coastal province with the largest economy and population in the YRB, the sustainable development of Shandong Province is of great importance in the region. This study evaluated the dynamic trend of sustainability levels of the nine cities in Shandong Province in the YRB through emergy analysis. Emergy-based indicators were established and analyzed from 2010 to 2019, taking account of the ecological service emergy (ESE) needed to dilute pollutants and emergy equivalent loss (EEL) on ecosystem quality and human health damage. Results showed that emergy sustainable indicators (ESI) in Tai'an, Heze, Dezhou, and Liaocheng ranged from 1 to 10, which had the potential for sustainable development. The ESI value of Jinan, Jining, Zibo, Dongying, and Binzhou was less than 1, which indicated that these cities were under great ecological pressure. The value of emergy indicators for sustainable development (EISD) of the nine cities all declined from 2010 to 2016, but remained stable from 2017 to 2019. Based on findings from the emergy analysis regarding policy implications and local conditions, the study concludes by providing proposals to improve regional sustainability.

Carbon footprint and embodied carbon transfer at the provincial level of the Yellow River Basin.

The ecological conservation and high-quality development of China's Yellow River Basin is a national strategy proposed in 2019. Under China's goal of achieving a carbon peak by 2030 and carbon neutrality by 2060, clarifying the carbon footprint of each province and the transfer paths of embodied carbon emissions is crucial to the carbon reduction strategy for this region. This paper uses input-output model and multi-regional input-output model to account for the carbon footprint of nine provinces in the Yellow River Basin, and to estimate the amount of embodied carbon transfer between provinces and industrial sectors. Social network analysis is applied to identify the critical industries in the inter-provincial embodied carbon emission transfers from the three major industries. We found that the per capita carbon footprint of the Yellow River Basin decreased by 23.4% in 2017 compared to 2012. Among the sectoral composition of the carbon footprint of each province, "Processing and manufacturing of petroleum, coking, nuclear fuel, and chemical products", "Construction", "Other services", and "Metal processing and metal, non-metallic products" are the four sectors with a higher proportion of emissions. The embodied carbon emission transfer between the provinces in middle and lower reaches of the Yellow River Basin is much higher than that between the upstream provinces. Among carbon emission transfer network of three major industries in nine provinces，the secondary industry in Shaanxi has the highest centrality and is the most critical industry. This study provides a theoretical basis and data support for formulating carbon emission reduction plans in the Yellow River Basin.

Radiosensitization of glioma cells by TP53-induced glycolysis and apoptosis regulator knockdown is dependent on thioredoxin-1 nuclear translocation.

TP53-induced glycolysis and apoptosis regulator (TIGAR) knockdown is proven to radiosensitize glioma cells, but the mechanisms are not fully understood. Thioredoxin-1 (TRX1) is a redox-sensitive oxidoreductase, which plays critical roles in DNA damage signal transduction via nuclear translocation in irradiated cells. Because the TRX1-dependent DNA damage signaling pathway relies on NADPH to maintain the reduced state of TRX1, and TIGAR functions to increase NADPH generation under oxidative stress, in this study, the role of TRX1 in TIGAR abrogation-induced radiosensitization was investigated. It was demonstrated that ionizing radiation (IR)-induced nuclear translocation of TRX1 was significantly inhibited by TIGAR interference and reversed by wild-type (WT)-TRX1 overexpression. In addition, WT-TRX1 overexpression could accelerate the process of DNA damage repair postponed by TIGAR knockdown in irradiated glioma cells. The reduction process of IR-oxidized TRX1 was also delayed by TIGAR knockdown but restored by WT-TRX1 overexpression. Therefore, we conclude that TIGAR knockdown-induced radiosensitization of glioma cells may be dependent on the inhibition of TRX1 nuclear translocation.