We report the electronic structure of the iron-chalcogenide superconductor, Fe 1.04 ͑Te 0.66 Se 0.34 ͒, obtained with high-resolution angle-resolved photoemission spectroscopy and density-functional calculations. In photoemission measurements, various photon energies and polarizations are exploited to study the Fermi surface topology and symmetry properties of the bands. The measured band structure and their symmetry characters qualitatively agree with our density-functional theory calculations of Fe͑Te 0.66 Se 0.34 ͒, although the band structure is renormalized by about a factor of three. We find that the electronic structures of this iron chalcogenides and the iron pnictides have many aspects in common; however, significant differences exist near the ⌫ point. For Fe 1.04 Te 0.66 Se 0.34 , there are clearly separated three bands with distinct even or odd symmetry that cross the Fermi energy ͑E F ͒ near the zone center, which contribute to three holelike Fermi surfaces. Especially, both experiments and calculations show a holelike elliptical Fermi surface at the zone center. Moreover, no sign of spin density wave was observed in the electronic structure and susceptibility measurements of this compound.

The electronic structure of a new charge-density-wave/ superconductor system, 1T-CuxTiSe2, has been studied by photoemission spectroscopy. A correlated semiconductor band structure is revealed for the undoped case. With Cu doping, the charge density wave is suppressed by the raising of the chemical potential, while the superconductivity is enhanced by the enhancement of the density of states. Moreover, the strong scattering at high doping might be responsible for the suppression of superconductivity in that regime. [5,6,7], whereas it rarely exists in 1T structured compounds.Recently, the discovery of superconductivity in 1T-Cu x TiSe 2 has further enriched the physics of TMD's [8]. The undoped 1T-TiSe 2 is a CDW material, whose mechanism remains controversial after decades of research. For example, some considered the CDW a band-type Jahn-Teller effect, where the electronic energy is lowered through structural distortion [9,10]. Some considered it a realization of the excitonic CDW mechanism proposed by Kohn in the 1960's [11,12]; but different models were proposed to interpret the electronic structure, depending on whether system was argued to be a semimetal, or a semiconductor [13,14]. With Cu doping, it was found that the CDW transition temperature quickly drops, similar to other M x TiSe 2 's (M=Fe,Mn,Ta,V and Nb) [15,16,17,18]. Meanwhile, the superconducting phase emerges from x ∼ 0.04 and reaches the maximal transition temperature of 4.3K at x ∼ 0.08, then decreases to 2.8K at x ∼ 0.10. Quite remarkably, this phase diagram resembles those of the cuprate and heavy fermion superconductors [19], except here the competing order of superconductivity is the charge order, instead of the antiferromagnetic spin order. The presence of this ubiquitous phase diagram in 1T-Cu x TiSe 2 calls for a detailed study of its electronic structure. In particular, the information retrieved might help resolve the controversy on the CDW mechanism for 1T-TiSe 2 .We studied 1T-Cu x TiSe 2 with high resolution angle resolved photoemission spectroscopy (ARPES). A correlated semiconductor band structure of the undoped system is evidently illustrated, resolving a long-standing controversy. Cu doping is found to effectively enhance the density of states around the Fermi energy (E F ), which explains the enhancement of superconductivity. On the other hand, severe inelastic scattering was observed near the solubility limit, corresponding to the drop of superconducting transition temperature in that regime. With increased doping, chemical potential is raised, and signs of the weakening electron-hole coupling is discovered, which is responsible for the suppression of the CDW. Our results indicate that the seeming "competition" between CDW and superconductivity in the phase diagram is a coincidence caused by different effects of doping in this 1T compound, in contrast to the 2H-TMD case [3].1T-Cu x TiSe 2 single crystals were prepared by the vapor-transport technique, with doping x = 0, 0. 015, 0.025, 0.055, 0.065 and 0.11 (accurate within ...

Background: Bacterial infection is associated with gastric carcinogenesis. However, the relationship between nonbacterial components and gastric cancer (GC) has not been fully explored. We aimed to characterize the fungal microbiome in GC. Methods: We performed ITS rDNA gene analysis in cancer lesions and adjacent noncancerous tissues of 45 GC cases from Shenyang, China. Obtaining the OTUs and combining effective grouping, we carried out species identifications, alpha and beta diversity analyses, and FUNGuild functional annotation. Moreover, differences were compared and tested between groups to better investigate the composition and ecology of fungi associated with GC and find fungal indicators. Results: We observed significant gastric fungal imbalance in GC. Principal component analysis revealed separate clusters for the GC and control groups, and Venn diagram analysis indicated that the GC group showed a lower OTU abundance than the control. At the genus level, the abundances of 15 fungal biomarkers distinguished the GC group from the control, of which Candida ( p = 0.000246) and Alternaria ( p = 0.00341) were enriched in GC, while Saitozyma ( p = 0.002324) and Thermomyces ( p = 0.009158) were decreased. Combining the results of Welch's t test and Wilcoxon rank sum test, Candida albicans ( C. albicans ) was significantly elevated in GC. The species richness Krona pie chart further revealed that C. albicans occupied 22% and classified GC from the control with an area under the receiver operating curve (AUC) of 0.743. Random forest analysis also confirmed that C. albicans could serve as a biomarker with a certain degree of accuracy. Moreover, compared with that of the control, the alpha diversity index was significantly reduced in the GC group. The Jaccard distance index and the Bray abundance index of the PCoA clarified separate clusters between the GC and control groups at the species level ( p = 0.00051). Adonis (PERMANOVA) analysis and ANOVA showed that there were significant differences in fungal structure among groups ( p = 0.001). Finally, FUNGuild functional classification predicted that saprotrophs were the most abundant taxa in the GC group. Conclusions: This study revealed GC-associated mycobiome imbalance characterized by an altered fungal composition and ecology and demonstrated that C. albicans can be a fungal biomarker for GC. With the significant increase of C. albicans in GC, the abundance of Fusicolla acetilerea, Arcopilus aureus, Fusicolla aquaeductuum were increased, while Candida glabrata, Aspergillus monte...

Cancer cells metabolize different energy sources to generate biomass rapidly. The purine biosynthetic pathway was recently identified as an important source of metabolic intermediates for these processes. However, very little was known about the regulatory mechanisms of purine metabolism in hepatocellular carcinoma (HCC). We explored the role of dual-specificity tyrosine (Y) phosphorylation-regulated kinase 3 (Dyrk3) in HCC metabolism. Dyrk3 was significantly down-regulated in HCC compared with normal controls. Its introduction in HCC cells markedly suppressed tumor growth and metastasis in xenograft tumor models. Mass spectrometric analysis of metabolites suggests that the effect of Dyrk3 on HCC occurred at least partially through down-regulating purine metabolism, as evidenced by the fact that inhibiting purine synthesis reverted the HCC progression mediated by the loss of Dyrk3. We further provide evidence that this action of Dyrk3 knockdown requires nuclear receptor coactivator 3 (NCOA3), which has been shown to be a coactivator of activating transcription factor 4 (ATF4) to target purine pathway genes for transcriptional activation. Mechanistically, Dyrk3 directly phosphorylated NCOA3 at Ser-1330, disrupting its binding to ATF4 and thereby causing the inhibition of ATF4 transcriptional activity. However, the phosphorylation-resistant NCOA3-S1330A mutant has the opposite effect. Interestingly, the promoter activity of Dyrk3 was negatively regulated by ATF4, indicating a double-negative feedback loop. Importantly, levels of Dyrk3 and phospho-NCOA3-S1330 inversely correlate with the expression of ATF4 in human HCC specimens. Conclusion: Our findings not only illustrate a function of Dyrk3 in reprograming HCC metabolism by negatively regulating NCOA3/ATF4 transcription factor complex but also identify NCOA3 as a phosphorylation substrate of Dyrk3, suggesting the Dyrk3/NCOA3/ATF4 axis as a potential candidate for HCC therapy. (Hepatology 2019;70:1785-1803).D ual-specificity tyrosine (Y) phosphorylation-regulated kinase 3 (Dyrk3) is one of five members of the mammalian kinase family which includes Dyrk1A, Dyrk1B, Dyrk2, Dyrk3, and Dyrk4. (1) Although this family shares a highly conserved amino acid sequence in the catalytic domain with a Tyr-X-Tyr motif in the activation loop, the individual members are totally different in their N-terminal and C-terminal regions. Numerous studies have confirmed the critical role of Dyrk family kinases in

UHMK1 is a nuclear serine/threonine kinase recently implicated in carcinogenesis. However, the functions and action mechanisms of UHMK1 in the pathogenesis of human gastric cancer (GC) are unclear. Here, we observed that UHMK1 was markedly upregulated in GC. UHMK1 silencing strongly inhibited GC aggressiveness. Interestingly, UHMK1‐induced GC progression was mediated primarily via enhancing de novo purine synthesis because inhibiting purine synthesis reversed the effects of UHMK1 overexpression. Mechanistically, UHMK1 activated ATF4, an important transcription factor in nucleotide synthesis, by phosphorylating NCOA3 at Ser (S) 1062 and Thr (T) 1067. This event significantly enhanced the binding of NCOA3 to ATF4 and the expression of purine metabolism‐associated target genes. Conversely, deficient phosphorylation of NCOA3 at S1062/T1067 significantly abrogated the function of UHMK1 in GC development. Clinically, Helicobacter pylori and GC‐associated UHMK1 mutation induced NCOA3‐S1062/T1067 phosphorylation and enhanced the activity of ATF4 and UHMK1. Importantly, the level of UHMK1 was significantly correlated with the level of phospho‐NCOA3 (S1062/T1067) in human GC specimens. Collectively, these results show that the UHMK1‐activated de novo purine synthesis pathway significantly promotes GC development.