Epigenetic gene regulation and metabolism are highly intertwined, yet little is known about whether altered epigenetics influence cellular metabolism during cancer progression. Here, we show that ...EZH2 and NRAS
mutations cooperatively induce progression of myeloproliferative neoplasms to highly penetrant, transplantable, and lethal myeloid leukemias in mice. EZH1, an EZH2 homolog, is indispensable for EZH2-deficient leukemia-initiating cells and constitutes an epigenetic vulnerability. BCAT1, which catalyzes the reversible transamination of branched-chain amino acids (BCAA), is repressed by EZH2 in normal hematopoiesis and aberrantly activated in EZH2-deficient myeloid neoplasms in mice and humans. BCAT1 reactivation cooperates with NRAS
to sustain intracellular BCAA pools, resulting in enhanced mTOR signaling in EZH2-deficient leukemia cells. Genetic and pharmacologic inhibition of BCAT1 selectively impairs EZH2-deficient leukemia-initiating cells and constitutes a metabolic vulnerability. Hence, epigenetic alterations rewire intracellular metabolism during leukemic transformation, causing epigenetic and metabolic vulnerabilities in cancer-initiating cells. SIGNIFICANCE: EZH2 inactivation and oncogenic NRAS cooperate to induce leukemic transformation of myeloproliferative neoplasms by activating BCAT1 to enhance BCAA metabolism and mTOR signaling. We uncover a mechanism by which epigenetic alterations rewire metabolism during cancer progression, causing epigenetic and metabolic liabilities in cancer-initiating cells that may be exploited as potential therapeutics.
.
.
Path planning is one of the key parts of unmanned aerial vehicle (UAV) fast autonomous flight in an unknown cluttered environment. However, real-time and stability remain a significant challenge in ...the field of path planning. To improve the robustness and efficiency of the path planning method in complex environments, this paper presents RETRBG, a robust and efficient trajectory replanning method based on the guiding path. Firstly, a safe guiding path is generated by using an improved A* and path pruning method, which is used to perceive the narrow space in its surrounding environment. Secondly, under the guidance of the path, a guided kinodynamic path searching method (GKPS) is devised to generate a safe, kinodynamically feasible and minimum-time initial path. Finally, an adaptive optimization function with two modes is proposed to improve the optimization quality in complex environments, which selects the optimization mode to optimize the smoothness and safety of the path according to the perception results of the guiding path. The experimental results demonstrate that the proposed method achieved good performance both in different obstacle densities and different resolutions. Compared with the other state-of-the-art methods, the quality and success rate of the planning result are significantly improved.
A
bstract
We investigate general features of the evolution of holographic subregion complexity (HSC) on Vaidya-AdS metric with a general form. The spacetime is dual to a sudden quench process in ...quantum system and HSC is a measure of the “difference” between two mixed states. Based on the subregion CV (Complexity equals Volume) conjecture and in the large size limit, we extract out three distinct stages during the evolution of HSC: the stage of linear growth at the early time, the stage of linear growth with a slightly small rate during the intermediate time and the stage of linear decrease at the late time. The growth rates of the first two stages are compared with the Lloyd bound. We find that with some choices of certain parameter, the Lloyd bound is always saturated at the early time, while at the intermediate stage, the growth rate is always less than the Lloyd bound. Moreover, the fact that the behavior of CV conjecture and its version of the subregion in Vaidya spacetime implies that they are different even in the large size limit.
Abstract
Light-induced halide segregation constrains the photovoltaic performance and stability of wide-bandgap perovskite solar cells and tandem cells. The implementation of an intermixed ...two-dimensional/three-dimensional heterostructure via solution post-treatment is a typical strategy to improve the efficiency and stability of perovskite solar cells. However, owing to the composition-dependent sensitivity of surface reconstruction, the conventional solution post-treatment is suboptimal for methylammonium-free and cesium/bromide-enriched wide-bandgap PSCs. To address this, we develop a generic three-dimensional to two-dimensional perovskite conversion approach to realize a preferential growth of wider dimensionality (n ≥ 2) atop wide-bandgap perovskite layers (1.78 eV). This technique involves depositing a well-defined MAPbI
3
thin layer through a vapor-assisted two-step process, followed by its conversion into a two-dimensional structure. Such a two-dimensional/three-dimensional heterostructure enables suppressed light-induced halide segregation, reduced non-radiative interfacial recombination, and facilitated charge extraction. The wide-bandgap perovskite solar cells demonstrate a champion power conversion efficiency of 19.6% and an open-circuit voltage of 1.32 V. By integrating with the thermal-stable FAPb
0.5
Sn
0.5
I
3
narrow-bandgap perovskites, our all-perovskite tandem solar cells exhibit a stabilized PCE of 28.1% and retain 90% of the initial performance after 855 hours of continuous 1-sun illumination.
As a cross-camera retrieval problem, person re-identification (ReID) suffers from image style variations caused by camera parameters, lighting and other reasons, which will seriously affect the model ...recognition accuracy. To address this problem, this paper proposes a two-stage contrastive learning method to gradually reduce the impact of camera variations. In the first stage, we train an encoder for each camera using only images from the respective camera. This ensures that each encoder has better recognition performance on images from its respective camera while being unaffected by camera variations. In the second stage, we encode the same image using all trained encoders to generate a new combination code that is robust against camera variations. We also use Cross-Camera Encouragement (Lin et al., in: Proceedings of the IEEE/CVF conference on computer vision and pattern recognition, 2020) distance that complements the advantages of combined encoding to further mitigate the impact of camera variations. Our method achieves high accuracy on several commonly used person ReID datasets, e.g., on the Market-1501, achieves 90.8% rank-1 accuracy and 85.2% mAP, outperforming the recent unsupervised works by 12+% in terms of mAP. Code is available at
https://github.com/yjwyuanwu/SET.
To further understand the toxic effects of bisphenol Z (BPZ) and bisphenol C (BPC) on aquatic organisms, zebrafish (
) were exposed to 0.02 mg/L BPZ and BPC mixed solution in the laboratory for 28 ...days. The impacts of BPZ and BPC on the activity of the antioxidant enzymes, expression of antioxidant genes, and estrogen receptor genes in zebrafish under different pH conditions were studied. The changes of glutathione peroxidase (GSH-Px), reduced glutathione (GSH), total superoxide dismutase (T-SOD), catalase (POD), and malondialdehyde (MDA) in the zebrafish were detected by spectrophotometry. The mRNA relative expression levels of CAT, GSH, SOD, ER
and ERb1 in the experimental group were determined by fluorescence quantitative PCR. The results showed that SOD activity and MDA content were inhibited under different pH conditions, and the activities of GSH, GSH-Px, and POD were induced. The activities of POD and GSH induced in the neutral environment were stronger than those in an acidic and alkaline environment. The mRNA relative expression levels of SOD and GSH were consistent with the activities of SOD and GSH. The mRNA relative expression levels of CAT were induced more strongly in the neutral environment than in acidic and alkaline conditions, the mRNA relative expression levels of ER
were induced most weakly in a neutral environment, and the mRNA relative expression levels of ER
1 were inhibited the most in a neutral environment.
The spatiotemporal control of 3D genome is fundamental for gene regulation, yet it remains challenging to profile high-resolution chromatin structure at cis-regulatory elements (CREs). Using ...C-terminally biotinylated dCas9, endogenous biotin ligases, and pooled sgRNAs, we describe the dCas9-based CAPTURE method for multiplexed analysis of locus-specific chromatin interactions. The redesigned system allows for quantitative analysis of the spatial configuration of a few to hundreds of enhancers or promoters in a single experiment, enabling comparisons across CREs within and between gene clusters. Multiplexed analyses of the spatiotemporal configuration of erythroid super-enhancers and promoter-centric interactions reveal organizational principles of genome structure and function.
Pasting, cooking, and digestible properties of Japonica rice with different amylose contents were investigated. Low-, medium-, and high-amylose Japonica rice (waxy, 18.8% amylose content, and 33.3% ...amylose content) were cooked and evaluated for water absorption, volume expansion, molecular mobility, microstructure, crystalline structure, and starch digestibility. The results showed that high-amylose rice had lower peak viscosity but higher pasting temperature and final viscosity than low- and medium-amylose rice. After cooking, high-amylose rice showed slightly higher water absorption ratio but lower volume expansion ratio than the other two rice varieties. Water was more evenly distributed in cooked low- and medium-amylose rice than in cooked high-amylose rice. After cooking, starch in low- and medium-amylose rice kernels almost lost the entire crystalline structure, but starch of cooked high-amylose rice still exhibited strong V-type crystallinity. Cooked high-amylose rice contained higher content of resistant starch than cooked rice of other two varieties.
PDF
