Search

Methionine adenosyltransferase 1A (MAT1A) is a tumor suppressor downregulated in hepatocellular carcinoma and cholangiocarcinoma, two of the fastest rising cancers worldwide. We compared MATα1 (protein encoded by MAT1A) interactome in normal versus cancerous livers by mass spectrometry to reveal interactions with 14-3-3ζ. The MATα1/14-3-3ζ complex was critical for the expression of 14-3-3ζ. Similarly, the knockdown and small molecule inhibitor for 14-3-3ζ (BV02), and ChIP analysis demonstrated the role of 14-3-3ζ in suppressing MAT1A expression. Interaction between MATα1 and 14-3-3ζ occurs directly and is enhanced by AKT2 phosphorylation of MATα1. Blocking their interaction enabled nuclear MATα1 translocation and inhibited tumorigenesis. In contrast, overexpressing 14-3-3ζ lowered nuclear MATα1 levels and promoted tumor progression. However, tumor-promoting effects of 14-3-3ζ were eliminated when liver cancer cells expressed mutant MATα1 unable to interact with 14-3-3ζ. Taken together, the reciprocal negative regulation that MATα1 and 14-3-3ζ exert is a key mechanism in liver tumorigenesis.

Background and aimsForkhead box M1 (FOXM1) and nuclear factor kappa B (NF-ĸB) are oncogenic drivers in liver cancer that positively regulate each other. We showed that methionine adenosyltransferase 1A (MAT1A) is a tumor suppressor in the liver and inhibits NF-ĸB activity. Here, we examined the interplay between FOXM1/NF-κB and MAT1A in liver cancer.Approach and resultsWe examined gene and protein expression, effects on promoter activities and binding of proteins to promoter regions, as well as effects of FOXM1 inhibitors T0901317 (T0) and forkhead domain inhibitory-6 (FDI-6) in vitro and in xenograft and syngeneic models of liver cancer. We found, in both hepatocellular carcinoma and cholangiocarcinoma, that an induction in FOXM1 and NF-κB expression is accompanied by a fall in MATα1 (protein encoded by MAT1A). The Cancer Genome Atlas data set confirmed the inverse correlation between FOXM1 and MAT1A. Interestingly, FOXM1 directly interacts with MATα1 and they negatively regulate each other. In contrast, FOXM1 positively regulates p50 and p65 expression through MATα1, given that the effect is lost in its absence. FOXM1, MATα1, and NF-κB all bind to the FOX binding sites in the FOXM1 and MAT1A promoters. However, binding of FOXM1 and NF-κB repressed MAT1A promoter activity, but activated the FOXM1 promoter. In contrast, binding of MATα1 repressed the FOXM1 promoter. MATα1 also binds and represses the NF-κB element in the presence of p65 or p50. Inhibiting FOXM1 with either T0 or FDI-6 inhibited liver cancer cell growth in vitro and in vivo. However, inhibiting FOXM1 had minimal effects in liver cancer cells that do not express MAT1A.ConclusionsWe have found a crosstalk between FOXM1/NF-κB and MAT1A. Up-regulation in FOXM1 lowers MAT1A, but raises NF-κB, expression, and this is a feed-forward loop that enhances tumorigenesis.

Although insulated-gate bipolar-transistor (IGBT) turn-on losses can be comparable to turn-off losses, IGBT turn-on has not been as thoroughly studied in the literature. In the present work IGBT turn on under resistive and inductive load conditions is studied in detail through experiments, finite element simulations, and circuit simulations using physics-based semiconductor models. Under resistive load conditions, it is critical to accurately model the conductivity-modulation phenomenon. Under clamped inductive load conditions at turn-on there is strong interaction between the IGBT and the freewheeling diode undergoing reverse recovery. Physics-based IGBT and diode models are used that have been proved accurate in the simulation of IGBT turn-off. Index Terms--Compact semiconductor device models, insulated-gate bipolar-transistor (IGBT) turn-on, interaction, physics-based semiconductor modeling.

This paper presents the development and implementation of a physics-based diode model which can simulate aspects of high-voltage diodes such as snappy recovery during punch-through and the modified carrier density profile due to local lifetime control. It uses a Fourier series solution for the ambipolar diffusion equation in the lightly doped base region. The model is compared with finite-element device simulations. A parameter extraction procedure for the diode with lifetime control is proposed in Part II. Index Terms--Lifetime control, physics-based model, p-i-n diode model, power semiconductor modeling, variable lifetime.

In this paper, a parameter extraction procedure for high-voltage diodes with local lifetime control is proposed. It is designed for use with the physics-based diode model described in Part I, which is capable of simulating diodes with local lifetime control. The parameter extraction procedure described requires a forward characteristic and a reverse recovery measurement. The parameter extraction procedure is illustrated using finite-element simulations. The physics-based model using the parameters extracted is then compared with experimental results. Index Terms--Lifetime control, physics-based model, p-i-n diode model, power semiconductor modeling, variable lifetime.

Summary: Citrus fruit has a unique structure with soft leathery peel and pulp containing vascular bundles and several segments with many juice sacs. The function and morphology of each fruit tissue are different. Therefore, analysis at the organ‐wide or mixed‐tissue level inevitably obscures many tissue‐specific phenomena. High‐throughput RNA sequencing was used to profile Citrus sinensis fruit development based on four fruit tissue types and six development stages from young fruits to ripe fruits. Using a coexpression network analysis, modules of coexpressed genes and hub genes of tissue‐specific networks were identified. Of particular, importance is the discovery of the regulatory network of phytohormones during citrus fruit development and ripening. A model was proposed to illustrate how ABF2 mediates the ABA signalling involved in sucrose transport, chlorophyll degradation, auxin homoeostasis, carotenoid and ABA biosynthesis, and cell wall metabolism during citrus fruit development. Moreover, we depicted the detailed spatiotemporal expression patterns of the genes involved in sucrose and citric acid metabolism in citrus fruit and identified several key genes that may play crucial roles in sucrose and citric acid accumulation in the juice sac, such as SWEET15 and CsPH8. The high spatial and temporal resolution of our data provides important insights into the molecular networks underlying citrus fruit development and ripening. [ABSTRACT FROM AUTHOR]

Background: Identifying a specific biomarker will facilitate the diagnosis and prediction of non-small cell lung cancer (NSCLC). The aim of this study was to investigate the serum SH2B1 in patients with NSCLC and healthy volunteers and establish a novel prediction model., Methods: A total 103 NSCLC patients and 108 healthy volunteers were selected from December 2019 to December 2020. Their serum and important clinical data were collected. Serum SH2B1 concentration was determined by ELISA. A novel prediction model for NSCLC was established according to these significant factors., Results: Multivariate logistic regression analysis indicated that the chronic pulmonary diseases; NLR ≥ 2.07; hemoglobin level ≥ 136.56 g/L; albumin level ≥ 42.59 g/L and serum SH2B1 concentration ≥615.28 pg/mL were considered as statistically significant difference (p < 0.05). A comprehensive nomogram was established based on serum SH2B1 concentration combined with significant clinical indicators to predict an individual's probability of NSCLC., Conclusion: The serum SH2B1 concentration ≥ 615.28 pg/mL is a significant predictive factor for NSCLC. Significantly, the prediction model based on serum SH2B1 has good stability and accuracy, which provides new insights of prediction assessment for NSCLC., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

We present a case of two-year old boy with solitary atypical adenomatous hyperplasia (AAH) in extralobar sequestration (ELS), which was misdiagnosed as diaphragmatic hernia before surgery. Review of AAH and pulmonary sequestration (PS) revealed that the present case is the youngest of solitary AAH and also the first report of solitary AAH arising in ELS without a primary lung cancer. In a sense, the present case firstly supports the hypothesis that ELS may be an underlying cancer predisposition syndrome, so aggressive surgical therapy should be recommended for ELS.