Surface hybridization of TiO2 with graphite‐like carbon layers of a few molecular layers thickness yields efficient photocatalysts. Photoelectrochemical measurements confirm an electronic interaction ...between TiO2 and the graphite‐like carbon. A TiO2 photocatalyst with a carbon shell of three molecular layers thickness (∼1 nm) shows the highest photocatalytic activity which is about two times higher than that of Degussa P25 TiO2 under UV light irradiation. The mechanism of the enhanced photocatalytic activity under UV irradiation is based on the high migration efficiency of photoinduced electrons at the graphite‐like carbon/TiO2 interface, which is due to the electronic interaction between both materials. In addition, a high activity under visible light irradiation is observed after graphite‐like carbon hybridization. TiO2's response is extended into the visible range of the solar spectrum due to the electronic coupling of π states of the graphite‐like carbon and conduction band states of TiO2.
Surface hybridization of TiO2 with graphite carbon produces efficient photocatalysts. The electronic contact between semiconductor and graphite layers results in the efficient separation of electron–hole pairs thereby minimizing electron–hole recombination. This leads to a higher photocatalytic activity under UV irradiation. This approach also extends TiO2's response into the visible range of the solar spectrum due to the electronic coupling of graphite‐carbon π states and conduction band states on the TiO2.
N6‐methyladenosine (m6A) modification regulatory proteins are involved in the development of many types of cancer. KIAA1429 serves as a scaffold in bridging the catalytic core components of the m6A ...methyltransferase complex. The role of KIAA1429 in gastric cancer and its related mechanism has not been reported upon. The expression of KIAA1429 was detected in human gastric cancer tissues and cell lines by quantitative real‐time polymerase chain reaction and western blot. The effects of KIAA1429 on gastric cancer proliferation were evaluated by cell counting kit assays, colony formation assays, flow cytometry assay, and in vivo experiments with nude mice. And messenger RNA (mRNA) high‐throughput sequencing, RNA immunoprecipitation assay (RIP), luciferase assay, and a rescue experiment were used to identify the relationship between KIAA1429 and its specific targeted gene, c‐Jun. We found that KIAA1429 was upregulated in gastric cancer tissues, and expressed lower in adjacent tissues. The upregulated KIAA1429 promoted proliferation and downregulated KIAA1429 was proved to inhibit proliferation of gastric cancer in vitro and in vivo. Then, we identified the potential KIAA1429 regulating gene as c‐Jun by mRNAs high‐throughput sequencing and RIP assay. By luciferase assay, we verified that KIAA1429 regulated the expression of c‐Jun in an m6A‐independent manner. Finally, the overexpression of c‐Jun rescued the inhibition of proliferation caused by KIAA1429 knockdown in gastric cancer cells. KIAA1429 could act as an oncogene in gastric cancer by stabilizing c‐Jun mRNA in an m6A‐independent manner. This highlights the functional role for KIAA1429 as a potential prognostic biomarker and therapeutic target in gastric cancer.
In this study, we provided in vitro and in vivo evidence that KIAA1429 played a key role in promoting gastric cancer by regulating c‐Jun expression in an m6A independent manner. This finding has the potential to develop a new therapeutic target for the treatment of gastric cancer.
Zinc, an essential micronutrient, has a cancer preventive role. Zinc deficiency has been shown to contribute to the progression of esophageal cancer. Orai1, a store‐operated Ca2+ entry (SOCE) ...channel, was previously reported to be highly expressed in tumor tissues removed from patients with esophageal squamous cell carcinoma (ESCC) with poor prognosis, and elevation of its expression contributes to both hyperactive intracellular Ca2+ oscillations and fast cell proliferation in human ESCC cells. However, the molecular basis of cancer preventive functions of zinc and its association with Orai1‐mediated cell proliferation remains unknown. The present study shows that zinc supplementation significantly inhibits proliferation of ESCC cell lines and that the effect of zinc is reversible with N,N,N′,N′‐tetrakis (2‐pyridylmethyl) ethylenediamine, a specific Zn2+ chelator, whereas non‐ tumorigenic esophageal epithelial cells are significantly less sensitive to zinc treatment. Fluorescence live cell imaging revealed that extracellular Zn2+ exerted rapid inhibitory effects on Orai1‐mediated SOCE and on intracellular Ca2+ oscillations in the ESCC cells. Knockdown of Orai1 or expression of Orai1 mutants with compromised zinc binding significantly diminished sensitivity of the cancer cells to zinc treatment in both SOCE and cell proliferation analyses. These data suggest that zinc may inhibit cell proliferation of esophageal cancer cells through Orai1‐mediated intracellular Ca2+ oscillations and reveal a possible molecular basis for zinc‐induced cancer prevention and Orai1‐SOCE signaling pathway in cancer cells.—Choi, S., Cui, C., Luo, Y., Kim, S.‐H., Ko, J.‐K., Huo, X., Ma, J., Fu, L.‐W., Souza, R. F., Korichneva, I., Pan, Z. Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1. FASEB J. 32,404‐416 (2018). www.fasebj.org
Genetic studies have elucidated critical roles of Piwi proteins in germline development in animals, but whether Piwi is an actual disease gene in human infertility remains unknown. We report germline ...mutations in human Piwi (Hiwi) in patients with azoospermia that prevent its ubiquitination and degradation. By modeling such mutations in Piwi (Miwi) knockin mice, we demonstrate that the genetic defects are directly responsible for male infertility. Mechanistically, we show that MIWI binds the histone ubiquitin ligase RNF8 in a Piwi-interacting RNA (piRNA)-independent manner, and MIWI stabilization sequesters RNF8 in the cytoplasm of late spermatids. The resulting aberrant sperm show histone retention, abnormal morphology, and severely compromised activity, which can be functionally rescued via blocking RNF8-MIWI interaction in spermatids with an RNF8-N peptide. Collectively, our findings identify Piwi as a factor in human infertility and reveal its role in regulating the histone-to-protamine exchange during spermiogenesis.
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•Hiwi ubiquitination-deficient D-box mutations are detected in azoospermia patients•D-box mutant knockin mice display spermatogenic failure at late spermiogenesis•Stabilized MIWI ties RNF8 up in the cytoplasm to prevent histone ubiquitination•Blocking MIWI-RNF8 interaction functionally rescues defective spermiogenesis
Male infertility in mice and humans can result from mutations that stabilize the Piwi protein in late spermatids: sperm defects are due to aberrant histone retention, not piRNA misregulation.
The middle-lower reaches of the Yangtze River is one of the most important metallogenic belts in China, hosting numerous Cu–Fe–Au–Mo deposits. Previous chronological and geochemical investigations ...mostly focused on the magmatic rocks and associated deposits in the lower reaches of the river, but the timing and genesis of the Cu–Au–(Mo) mineralized porphyries in the middle reaches are yet to be well constrained. In this study we carried out precise SIMS U–Pb zircon age determinations for a number of Cu–Au–(Mo) mineralized porphyries and barren granitoid intrusions in the Jiurui and Edong mining districts in the middle reaches of the Yangtze River valley. Our new age results reveal two discrete magmatic and mineralization events at ca. 145–146
Ma and ca. 140
Ma in the study area. The ca. 145–146
Ma granitoids signify the start of the Cretaceous magmatism in the Yangtze River Metallogenic Belt, coinciding temporally with a regional tectonic switching from a Late Jurassic transpressive tectonic regime to an earliest Cretaceous extensional regime in eastern China.
►The Cu–Au–(Mo) mineralized porphyries and barren granitoids in the Jiurui and Edong mining districts in Yangtze River Metallogenic Belt were precisely dated at ca. 145–146
Ma and ca. 140
Ma. ►The ca. 145–146
Ma mineralized porphyries and barren granitoids signify the initiation of the Cretaceous magmatism in the Yangtze River Metallogenic Belt. ►These igneous rocks are most likely generated in response to the regional tectonic switch from the Late Jurassic transpressive to earliest Cretaceous extensional regimes.
Vinylene/olefin-linked two-dimensional covalent organic frameworks (v-2D-COFs) have emerged as advanced semiconducting materials with excellent in-plane conjugation, high chemical stabilities, and ...precisely tunable electronic structures. Exploring new linkage chemistry for the reticular construction of v-2D-COFs remains in infancy and challenging. Herein, we present a solid-state benzobisoxazole-mediated aldol polycondensation reaction for the construction of two novel isomeric benzobisoxazole-bridged v-2D-COFs (v-2D-COF-NO1 and v-2D-COF-NO2) with trans and cis configurations of benzobisoxazole. Interestingly, the isomeric benzobisoxazole linkers endow the two v-2D-COFs with distinct optoelectronic and electrochemical properties, ranging from light absorption and emission to charge-transfer properties. When employed as the photocathode, v-2D-COF-NO1 exhibits a photocurrent of up to ∼18 μA/cm2 under AM 1.5G irradiation at −0.3 V vs reversible hydrogen electrode (RHE), which is twice the value of v-2D-COF-NO2 (∼9.1 μA/cm2). With Pt as a cocatalyst, v-2D-COF-NO1 demonstrates a photocatalytic hydrogen evolution rate of ∼1.97 mmol h–1 g–1, also in clear contrast to that of v-2D-COF-NO2 (∼0.86 mmol h–1 g–1) under identical conditions. This work demonstrates the synthesis of v-2D-COFs via benzobisoxazole-mediated aldol polycondensation with isomeric structures and distinct photocatalytic properties.
Granulocyte-macrophage colony stimulating factor (GM-CSF) is a cytokine that is used as an immunopotentiator for anti-tumor therapies in recent years. We found that some of the extranodal natural ...killer/T cell lymphoma (ENKTL) patients with the treatment of hGM-CSF rapidly experienced disease progression, but the underlying mechanisms remain to be elucidated. Here, we aimed to explore the mechanisms of disease progression triggered by GM-CSF in ENKTL.
The mouse models bearing EL4 cell tumors were established to investigate the effects of GM-CSF on tumor growth and T cell infiltration and function. Human ENKTL cell lines including NK-YS, SNK-6, and SNT-8 were used to explore the expression of programmed death-ligand 1 (PD-L1) induced by GM-CSF. To further study the mechanisms of disease progression of ENKTL in detail, the mutations and gene expression profile were examined by next-generation sequence (NGS) in the ENKTL patient's tumor tissue samples.
The mouse-bearing EL4 cell tumor exhibited a faster tumor growth rate and poorer survival in the treatment with GM-CSF alone than in treatment with IgG or the combination of GM-CSF and PD-1 antibody. The PD-L1 expression at mRNA and protein levels was significantly increased in ENKTL cells treated with GM-CSF. STAT5A high-frequency mutation including p.R131G, p.D475N, p.F706fs, p.V707E, and p.S710F was found in 12 ENKTL cases with baseline tissue samples. Importantly, STAT5A-V706fs mutation tumor cells exhibited increased activation of STAT5A pathway and PD-L1 overexpression in the presence of GM-CSF.
These findings demonstrate that GM-CSF potentially triggers the loss of tumor immune surveillance in ENKTL patients and promotes disease progression, which is associated with STAT5 mutations and JAK2 hyperphosphorylation and then upregulates the expression of PD-L1. These may provide new concepts for GM-CSF application and new strategies for the treatment of ENKTL.
The polycomb group protein B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is dysregulated in various cancers, and its upregulation strongly correlates with an invasive phenotype and poor ...prognosis in patients with nasopharyngeal carcinomas. However, the underlying mechanism of Bmi-1-mediated invasiveness remains unknown. In the current study, we found that upregulation of Bmi-1 induced epithelial-mesenchymal transition (EMT) and enhanced the motility and invasiveness of human nasopharyngeal epithelial cells, whereas silencing endogenous Bmi-1 expression reversed EMT and reduced motility. Furthermore, upregulation of Bmi-1 led to the stabilization of Snail, a transcriptional repressor associated with EMT, via modulation of PI3K/Akt/GSK-3beta signaling. Chromatin immunoprecipitation assays revealed that Bmi-1 transcriptionally downregulated expression of the tumor suppressor PTEN in tumor cells through direct association with the PTEN locus. This in vitro analysis was consistent with the statistical inverse correlation detected between Bmi-1 and PTEN expression in a cohort of human nasopharyngeal carcinoma biopsies. Moreover, ablation of PTEN expression partially rescued the migratory/invasive phenotype of Bmi-1-silenced cells, indicating that PTEN might be a major mediator of Bmi-1-induced EMT. Our results provide functional and mechanistic links between the oncoprotein Bmi-1 and the tumor suppressor PTEN in the development and progression of cancer.
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