Disorder induced multifractal superconductivity in monolayer niobium dichalcogenides

The interplay between disorder and superconductivity is a subtle and fascinating phenomenon in quantum many body physics. The conventional superconductors are insensitive to dilute nonmagnetic impurities, known as the Anderson's theorem. Destruction of superconductivity and even superconductor-insulator transitions occur in the regime of strong disorder. Hence disorder-enhanced superconductivity is rare and has only been observed in some alloys or granular states. Because of the entanglement of various effects, the mechanism of enhancement is still under debate. Here we report well-controlled disorder effect in the recently discovered monolayer NbSe$_2$ superconductor. The superconducting transition temperatures of NbSe$_2$ monolayers are substantially increased by disorder. Realistic theoretical modeling shows that the unusual enhancement possibly arises from the multifractality of electron wave functions. This work provides the first experimental evidence of the multifractal superconducting state

Ether phospholipids metabolism is a latent vulnerability for pancreatic cancer resistance

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In Vivo Functional Platform Targeting Patient-Derived Xenografts Identifies WDR5-Myc Association as a Critical Determinant of Pancreatic Cancer

SummaryCurrent treatment regimens for pancreatic ductal adenocarcinoma (PDAC) yield poor 5-year survival, emphasizing the critical need to identify druggable targets essential for PDAC maintenance. We developed an unbiased and in vivo target discovery approach to identify molecular vulnerabilities in low-passage and patient-derived PDAC xenografts or genetically engineered mouse model-derived allografts. Focusing on epigenetic regulators, we identified WDR5, a core member of the COMPASS histone H3 Lys4 (H3K4) MLL (1–4) methyltransferase complex, as a top tumor maintenance hit required across multiple human and mouse tumors. Mechanistically, WDR5 functions to sustain proper execution of DNA replication in PDAC cells, as previously suggested by replication stress studies involving MLL1, and c-Myc, also found to interact with WDR5. We indeed demonstrate that interaction with c-Myc is critical for this function. By showing that ATR inhibition mimicked the effects of WDR5 suppression, these data provide rationale to test ATR and WDR5 inhibitors for activity in this disease

Glucose Metabolism in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers, with a five-year survival rate of around 5% to 8%. To date, very few available drugs have been successfully used to treat PDAC due to the poor understanding of the tumor-specific features. One of the hallmarks of pancreatic cancer cells is the deregulated cellular energetics characterized by the “Warburg effect”. It has been known for decades that cancer cells have a dramatically increased glycolytic flux even in the presence of oxygen and normal mitochondrial function. Glycolytic flux is the central carbon metabolism process in all cells, which not only produces adenosine triphosphate (ATP) but also provides biomass for anabolic processes that support cell proliferation. Expression levels of glucose transporters and rate-limiting enzymes regulate the rate of glycolytic flux. Intermediates that branch out from glycolysis are responsible for redox homeostasis, glycosylation, and biosynthesis. Beyond enhanced glycolytic flux, pancreatic cancer cells activate nutrient salvage pathways, which includes autophagy and micropinocytosis, from which the generated sugars, amino acids, and fatty acids are used to buffer the stresses induced by nutrient deprivation. Further, PDAC is characterized by extensive metabolic crosstalk between tumor cells and cells in the tumor microenvironment (TME). In this review, we will give an overview on recent progresses made in understanding glucose metabolism-related deregulations in PDAC

Functional Elucidation and Methylation-Mediated Downregulation of ITGA5 Gene in Breast Cancer Cell Line MDA-MB-468

Expression level of integrin alpha 5 in tumor cells has been indicated to be involved in cell proliferation and organ-specific metastasis We previously demonstrated that ITGA5 expression was downregulated in the high invasive MDA-MB-468 cells compared with other breast cancer cell lines. In this study, we found that the methylation status in the region around transcriptional start site of ITGA5 gene was increased in MDA-MB-468 cells Overexpression of integrin alpha 5 on MDA-MB-468 cells resulted in cell growth inhibition, which could be reversed by adhesion to fibronectin Cell adhesion and spreading to fibronectin was enhanced after ITGA5 was overexpressed in MDA-MB-468 cells, while cell migration was attenuated. Knockdown of ITGA5 in MCF-7 cells led to cell growth inhibition but had little influence on cell migration These findings indicated the diverse roles of ITGA5 expression in breast cancer cells J Cell Biochem 110 1130-1141, 2010 (C) 2010 Wiley-Liss. In

Hydrate Formation and Decomposition Regularities in Offshore Gas Reservoir Production Pipelines

In recent years, the exploitation and utilization of offshore oil and gas resources have attracted more attention. In offshore gas reservoir production, wellbore temperature and pressure change continuously when water-bearing natural gas flows upward. The wellbore temperature is also affected by the low-temperature sea water. The combination of temperatures and pressures controlled by the upward flow, and cooling from the surrounding seawater frequently leads to the conditions of temperature and pressure for hydrate formation. This can lead to pipeline blockage and other safety accidents. In this study, we utilize mathematical models of hydrate phase equilibrium, wellbore temperature, wellbore pressure to study hydrate formation and decomposition in offshore gas reservoir production. Numerical solution algorithms are developed and numerical solutions are validated. The sensitivity influence of different parameters on the regions and regularities of hydrate formation and decomposition in wellbores are obtained through numerical simulations. It is found that increased daily gas production, water content, or geothermal gradient in offshore gas reservoir production pipelines results in less hydrate formation in the wellbores. Accordingly, the risk of wellbore blockage decreases and production safety is maintained. Decreased tubing head pressure or seawater depth results in similar effects. The result of this study establishes a set of prediction methods for hydrate formation and decomposition that can be used in the development of guidelines for safe construction design

H3K9ac and HDAC2 Activity Are Involved in the Expression of Monocarboxylate Transporter 1 in Oligodendrocyte

Recently, it is reported that monocarboxylate transporter 1 (MCT1) plays crucial role in oligodendrocyte differentiation and myelination. We found that MCT1 is strongly expressed in oligodendrocyte but weakly expressed in oligodendrocyte precursors (OPCs), and the underlying mechanisms remain elusive. Histone deacetylases (HDACs) activity is required for induction of oligodendrocyte differentiation and maturation. We asked whether HDACs are involved in the regulation of MCT1 expression. This work revealed that the acetylation level of histone H3K9 (H3K9ac) was much higher in mct1 gene (Slc16a1) promoter in OPCs than that in oligodendrocyte. H3K9ac regulates MCT1 expression was confirmed by HDAC acetyltransferase inhibitors trichostatin A and curcumin. Of note, there was a negative correlation between H3K9ac and MCT1 expression in oligodendrocyte. Further, we found that the levels of HDAC1, 2, and 3 protein in oligodendrocyte were obviously higher than those in OPCs. However, specific knockdown of HDAC2 but not HDAC1 and HDAC3 significantly decreased the expression of MCT1 in oligodendrocyte. Conversely, overexpression of HDAC2 remarkably enhanced the expression of MCT1. The results imply that HDAC2 is involved in H3K9ac modification which regulates the expression of MCT1 during the development of oligodendrocyte

Synthesis and anticancer evaluations of novel 1H-imidazole [4,5-f][1,10] phenanthroline derivative for the treatment of colorectal cancer

1H-imidazole [4,5-f][1,10] phenanthroline is a promising chemical structure for cancer treatment. Herein, we synthesized a novel 1H-imidazole [4,5-f][1,10] phenanthroline derivative named IPM714 and found it exhibited selectively colorectal cancer (CRC) cells inhibitory activities, with half maximal inhibitory concentration (IC50) of 1.74 μM and 2 μM in HCT116 cells and SW480 cells, respectively. The present study is intended to explore the cytotoxicity of IPM714 in cancer cells of various types and its anticancer mechanism in vitro. Cellular functional analyses indicated IPM714 can arrest HCT116 cell cycle in S phase and induce apoptosis in HCT116 and SW480 cells. Western blot and molecular docking showed that IPM714 may suppress PI3K/AKT/mTOR pathway to inhibit cell proliferation and regulate cell cycle as well as apoptosis. This study proved IPM714 to be a promising drug in CRC therapy