Epstein-Barr virus-encoded EBNA1 inhibits the canonical NF-κB pathway in carcinoma cells by inhibiting IKK phosphorylation

Background The Epstein-Barr virus (EBV)-encoded EBNA1 protein is expressed in all EBV-associated tumours, including undifferentiated nasopharyngeal carcinoma (NPC), where it is indispensable for viral replication, genome maintenance and viral gene expression. EBNA1's transcription factor-like functions also extend to influencing the expression of cellular genes involved in pathways commonly dysregulated during oncogenesis, including elevation of AP-1 activity in NPC cell lines resulting in enhancement of angiogenesis in vitro. In this study we sought to extend these observations by examining the role of EBNA1 upon another pathway commonly deregulated during carcinogenesis; namely NF-κB. Results In this report we demonstrate that EBNA1 inhibits the canonical NF-κB pathway in carcinoma lines by inhibiting the phosphorylation of IKKα/β. In agreement with this observation we find a reduction in the phosphorylation of IκBα and reduced phosphorylation and nuclear translocation of p65, resulting in a reduction in the amount of p65 in nuclear NF-κB complexes. Similar effects were also found in carcinoma lines infected with recombinant EBV and in the EBV-positive NPC-derived cell line C666-1. Inhibition of NF-κB was dependent upon regions of EBNA1 essential for gene transactivation whilst the interaction with the deubiquitinating enzyme, USP7, was entirely dispensable. Furthermore, in agreement with EBNA1 inhibiting p65 NF-κB we demonstrate that p65 was exclusively cytoplasmic in 11 out of 11 NPC tumours studied. Conclusions Inhibition of p65 NF-κB in murine and human epidermis results in tissue hyperplasia and the development of squamous cell carcinoma. In line with this, p65 knockout fibroblasts have a transformed phenotype. Inhibition of p65 NF-κB by EBNA1 may therefore contribute to the development of NPC by inducing tissue hyperplasia. Furthermore, inhibition of NF-κB is employed by viruses as an immune evasion strategy which is also closely linked to oncogenesis during persistent viral infection. Our findings therefore further implicate EBNA1 in playing an important role in the pathogenesis of NPC

Case report: Identification of atypical mantle cell lymphoma with CCND3 rearrangement by next-generation sequencing

The t(11;14) (q13;q32) translocation resulting in overexpression of cyclin D1 is the major oncogenic mechanism in mantle cell lymphoma (MCL). Most MCLs can be diagnosed based on morphological features, cyclin D1 expression, and IGH/CCND1 rearrangement. However, in some atypical cases where conventional FISH studies fail to detect IGH/CCND1 rearrangement or immunohistochemistry for cyclin D1 is negative, the diagnosis of the disease can be difficult. Hence, next-generation sequencing (NGS) may allow the identification of molecular alterations and assist in the diagnosis of atypical MCL. In this study, we reported a case of a patient diagnosed as asymptomatic MCL who presented with lymphadenopathy during the initial assessment. A lymph node biopsy was performed and the results revealed a high Ki67 index. However, initial diagnosis of aggressive MCL was difficult since the IGH/CCND1 rearrangement result was negative. Ultimately, by the aid of NGS we identified a rare CCND3 rearrangement in the patient, which lead to overexpression of cyclin D3, thereby facilitating the diagnosis of MCL

Dirac Cosmology and the Acceleration of the Contemporary Universe

A model is suggested to unify the Einstein GR and Dirac Cosmology. There is one adjusted parameter $b_2$ in our model. After adjusting the parameter $b_2$ in the model by using the supernova data, we have calculated the gravitational constant $\bar G$ and the physical quantities of $a(t)$, $q(t)$ and $\rho_r(t)/ \rho_b(t)$ by using the present day quantities as the initial conditions and found that the equation of state parameter $w_{\theta}$ equals to -0.83, the ratio of the density of the addition creation $\Omega_{\Lambda}=0.8$ and the ratio of the density of the matter including multiplication creation, radiation and normal matter $\Omega_m =0.2$ at present. The results are self-consistent and in good agreement with present knowledge in cosmology. These results suggest that the addition creation and multiplication creation in Dirac cosmology play the role of the dark energy and dark matter.Comment: 13 pages, 8 figure

Gas Sensors Based on Electrospun Nanofibers

Nanofibers fabricated via electrospinning have specific surface approximately one to two orders of the magnitude larger than flat films, making them excellent candidates for potential applications in sensors. This review is an attempt to give an overview on gas sensors using electrospun nanofibers comprising polyelectrolytes, conducting polymer composites, and semiconductors based on various sensing techniques such as acoustic wave, resistive, photoelectric, and optical techniques. The results of sensing experiments indicate that the nanofiber-based sensors showed much higher sensitivity and quicker responses to target gases, compared with sensors based on flat films

Study on the Deformation Induced by Vertical Two-Layer Large Diameter Pipe-Jacking in the Soil-Rock Composite Stratum

Aiming at the features of deformation caused by large diameter vertical two-layer pipe jacking in the soil-rock composite stratum, on-site monitoring and numerical analysis has been done based on an electric power tunnel project constructed with the pipe jacking method, in which the upper tunnel is located in the soil layer and the lower tunnel is partially located in the rock layer. The research shows that: (1) During upper pipe jacking construction, the maximum transverse and longitudinal ground settlements are about three times those of the lower pipe jacking construction, and the maximum horizontal lateral displacement is about 3.3 times the lower pipe jacking construction. (2) Total ground settlement increases rapidly with the reduction of vertical clear spacing of the upper and lower pipe, and the superimposed effect should be taken into consideration during the vertical arranged pipe-jacking construction. (3) The Peck formula, which is used to estimate lateral surface subsidence distribution, is modified to make it more applicable in the soil–rock composite stratum to calculate the ground settlement induced by the construction of pipe-jacking

Study on Transverse Seismic Response Characteristics of Large Diameter Vertical Double-Layer Overlapping Pipe Jacking in the Soil-Rock Composite Stratum

The sharp change of stiffness in the soil–rock combination stratum is the weak point in the seismic design of the pipe jacking structure. To study the seismic response characteristics of vertical double-layer overlapping pipe jacking, based on the typical soil–rock combination strata in Jinan, two electric power pipe jacking tunnels of 3.6 m diameter were studied as the research objects, where the upper pipe jacking is located in the soil and the lower pipe jacking is located in the composite stratum of half soil and half rock. The soil–rock-overlapping tunnel system was deemed as a plane strain problem. By using the dynamic time history method and considering the non-linearity of material, the seismic response characteristics of a vertical overlapping pipe jacking tunnel under seismic wave were discussed from five aspects, acceleration response, displacement response, stress response, soil interlayer response and the influence of soil–rock combination stratum. The results indicate that under the action of ground motion, the peak acceleration and relative horizontal displacement of the upper pipe jacking are greater than those of the lower pipe jacking; small pipe jacking spacing will lead to the aggravating earthquake failure effect; due to the stiffness difference, the relative horizontal displacement and stress of pipe jacking structure at the soil–rock interface change abruptly. The vertical double-layer arrangement of the pipe jacking increases the buried depth, and the stratum is prone to be uneven hardness. Therefore, the seismic design and relevant structural measures of large diameter vertical overlapping pipe jacking structure should be strengthened

The Diagnostic Value of Serum PIVKA-II Alone or in Combination with AFP in Chinese Hepatocellular Carcinoma Patients

Background. At present, the diagnostic accuracy of alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance is insufficient. It remains controversial whether prothrombin induced by vitamin K absence II (PIVKA-II) has a better diagnostic value than AFP for HCC patients. Objective. To investigate the diagnostic role of PIVKA-II alone or in combination with AFP in Chinese HCC patients. Methods. Serum AFP and PIVKA-II levels were detected and analyzed in 308 HCC afflicted patients and 120 unafflicted controls. The receiver operator curve (ROC) and area under the curve (AUC) were conducted to evaluate the clinical value of AFP and PIVKA-II for diagnosing HCC and early HCC. Results. In the whole HCC cohort, the diagnostic values of PIVKA-II were better than that of AFP. The AUC of PIVKA-II and AFP was 0.90 (95% CI 0.87-0.94) and 0.79 (95% CI 0.74-0.84), respectively. “AFP + PIVKA-II” yielded a high sensitivity of 95.1% and a specificity of 83.3%, with the AUC 0.89 (95% CI 0.85-0.93). In the early stage HCC group, the diagnostic accuracy of PIVKA-II was also better than that of AFP. The AUC of PIVKA-II and AFP was 0.83 (95% CI 0.77-0.89) and 0.75 (95% CI 0.68-0.81), respectively. “AFP + PIVKA-II” achieved the sensitivity of 83.3% and specificity of 89.1%, with an AUC of 0.86 (95% CI 0.81-0.91). Moreover, for AFP-negative HCC patients, serum PIVKA-II showed good diagnostic performance, with an AUC of 0.804 (95% CI 0.720-0.887). Besides, elevated PIVKA-II level was a strong independent risk factor for HCC patients with portal vein tumor thrombus (PVTT) (OR=4.890, P=0.020). Conclusion. PIVKA-II is superior to AFP in HCC screening, and AFP in combination with PIVKA-II significantly improves the diagnostic value for Chinese HCC patients. PIVKA-II could effectively indicate HCC accompanied by PVTT and help to optimize the therapeutic strategy

Comprehension of the Synergistic Effect between m&t-BiVO4/TiO2-NTAs Nano-Heterostructures and Oxygen Vacancy for Elevated Charge Transfer and Enhanced Photoelectrochemical Performances

Through the utilization of a facile procedure combined with anodization and hydrothermal synthesis, highly ordered alignment TiO2 nanotube arrays (TiO2-NTAs) were decorated with BiVO4 with distinctive crystallization phases of monoclinic scheelite (m-BiVO4) and tetragonal zircon (t-BiVO4), favorably constructing different molar ratios and concentrations of oxygen vacancies (Vo) for m&t-BiVO4/TiO2-NTAs heterostructured nanohybrids. Simultaneously, the m&t-BiVO4/TiO2-NTAs nanocomposites significantly promoted photoelectrochemical (PEC) activity, tested under UV–visible light irradiation, through photocurrent density testing and electrochemical impedance spectra, which were derived from the positive synergistic effect between nanohetero-interfaces and Vo defects induced energetic charge transfer (CT). In addition, a proposed self-consistent interfacial CT mechanism and a convincing quantitative dynamic process (i.e., rate constant of CT) for m&t-BiVO4/TiO2-NTAs nanoheterojunctions are supported by time-resolved photoluminescence and nanosecond time-resolved transient photoluminescence spectra, respectively. Based on the scheme, the m&t-BiVO4/TiO2-NTAs-10 nanohybrids exhibited a photodegradation rate of 97% toward degradation of methyl orange irradiated by UV–visible light, 1.14- and 1.04-fold that of m&t-BiVO4/TiO2-NTAs-5 and m&t-BiVO4/TiO2-NTAs-20, respectively. Furthermore, the m&t-BiVO4/TiO2-NTAs-10 nanohybrids showed excellent PEC biosensing performance with a detection limit of 2.6 μM and a sensitivity of 960 mA cm−2 M−1 for the detection of glutathione. Additionally, the gas-sensing performance of m&t-BiVO4/TiO2-NTAs-10 is distinctly superior to that of m&t-BiVO4/TiO2-NTAs-5 and m&t-BiVO4/TiO2-NTAs-20 in terms of sensitivity and response speed