Metformin Decreases 2-HG Production through the MYC-PHGDH Pathway in Suppressing Breast Cancer Cell Proliferation

The biguanide drug metformin has been widely used for the treatment of type 2 diabetes, and there is evidence supporting the anticancer effect of metformin despite some controversy. Here, we report the growth inhibitory activity of metformin in the breast cancer (MCF-7) cells, both in vitro and in vivo, and the associated metabolic changes. In particular, a decrease in a well-known oncometabolite 2-hydroxyglutarate (2-HG) was discovered by a metabolomics approach. The decrease in 2-HG by metformin was accompanied by the reduction in histone methylation, consistent with the known tumorigenic mechanism of 2-HG. The relevance of 2-HG inhibition in breast cancer was also supported by a higher level of 2-HG in human breast cancer tissues. Genetic knockdown of PHGDH identified the PHGDH pathway as the producer of 2-HG in the MCF-7 cells that do not carry isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) mutations, the conventional producer of 2-HG. We also showed that metformin's inhibitory effect on the PHGDH-2HG axis may occur through the regulation of the AMPK-MYC pathway. Overall, our results provide an explanation for the coherent pathway from complex I inhibition to epigenetic changes for metformin's anticancer effect.Peer reviewe

Decomposed entropy and estimation of output power in deformed microcavity lasers

Park et al. [Phys. Rev. A 106, L031504 (2022)] showed that the Shannon entropy of the probability distribution of a single random variable for far-field profiles (FFPs) in deformed microcavity lasers can efficiently measure the directionality of deformed microcavity lasers. In this study, we instead consider two random variables of FFPs with joint probability distributions and introduce the decomposed (Shannon) entropy for the peak intensity of directional emissions. This provides a new foundation such that the decomposed entropy can estimate the degree of the output power at given FFPs without any further information.Comment: 7 pages, 5 figure

Environmental considerations of plastic behaviors for automobile applications

AbstractIt is well known fact that the thermo-mechanical behaviors of polymeric materials are strongly influenced by environmental factors, and, for automobiles, the mechanical properties of interior plastic structures are noticeably changed by being repeatedly exposed to environments such as sun light and rains. As the properties change, mechanical fits such as fasteners and clips in automobiles lose their tightness, creating unexpected noises. To consider Buzz, Squeak and Rattle (BSR) from initial stage of the interior design, it is very important to obtain, analyze and understand the structural behaviors of the materials under environmental changes as well as time. In this report, the mechanical property changes of the plastics for automobiles are measured to investigate the temperature and humidity effects. The samples are undergone different temperature and humidity conditions, and regularly taken out to measure the thermo-mechanical properties. The data are compared with the original samples, and analyzed for the properties change. Viscoelastic characteristics such as glass transition temperatures and storage/loss modulus were also investigate

Optimal Synthesis of Horizontally Aligned Single-Walled Carbon Nanotubes and Their Biofunctionalization for Biosensing Applications

As an influential candidate for highly sensitive biomolecule sensor, which can capture disease related biomolecules, carbon nanotube is useful material due to its unique properties. To adopt as a sensing platform, it is strongly needed to find optimal refined synthetic condition. In order to find the optimal synthetic conditions of horizontally aligned CNT, we performed quantity control of themixed gases of H-2 and CH4 injected. We successfully find that the formation of amorphous-like carbon was critically affected by some gas condition such as the flow rate of injected gases and ratios of gas mixture. Moreover, it should be noted that our horizontally aligned carbon nanotube array platform developed would offer another potential in developing nanoscale light source, where light emission results from electron-hole carrier recombinationope

Residential Development and Hierarchical Governance: Multifamily Housing and Multilevel Analysis

This study investigates factors that influence multifamily housing zoning from a hierarchical governance perspective. Local zoning is a product of interactive processes among various stakeholders and of local politics. Since local zoning represents community interests in land development and has an exclusionary characteristic, multifamily housing zoning is controversial in some localities. We hypothesize that a hierarchical governance structure influences the supply of local multifamily housing zoning. The result of a hierarchical generalized linear model shows evidence that state smart growth reform and state intervention in local land use are positively associated with the establishment of local multifamily housing zoning. The decisions are also affected by local factors such as the supply of land, density restrictions, cost of new infrastructure, and city budget constraints. This study concludes that state authority and smart growth reform make it possible for local governments to commit to multifamily housing zoning to achieve housing affordability and high-density development