A regulator of the protein phosphatase 2A (PP2A), α4, has been implicated in a variety of functions that regulate many cellular processes. To explore the role of α4 in human cell transformation and ...tumorigenesis, we show that α4 is highly expressed in human cells transformed by chemical carcinogens including benzo(a)pyrene, aflatoxin B(1), N-methyl-N'-nitro-N-nitrosoguanidine, nickel sulfate and in several hepatic and lung cancer cell lines. In addition, overexpression of α4 was detected in 87.5% (74/80) of primary hepatocellular carcinomas, 84.0% (21/25) of primary lung cancers and 81.8% (9/11) of primary breast cancers, indicating that α4 is ubiquitously highly expressed in human cancer. Functional studies revealed that elevated α4 expression results in an increase in cell proliferation, promotion of cell survival and decreased PP2A-attributable activity. Importantly, ectopic expression of α4 permits non-transformed human embryonic kidney cells (HEKTER) and L02R cells to form tumors in immunodeficient mice. Furthermore, we show that the highly expressed α4 in transformed cells or human tumors is not regulated by DNA hypomethylation. A microRNA, miR-34b, that suppresses the expression of α4 through specific binding to the 3'-untranslated region of α4 is downregulated in transformed or human lung tumors. Taken together, these observations identify that α4 possesses an oncogenic function. Reduction of PP2A activity due to an enhanced α4-PP2A interaction contributes directly to chemical carcinogen-induced tumorigenesis.
To reduce the cost of bacterial cellulose (BC) production, the possibility of using acetone‐butanol‐ethanol (ABE) fermentation wastewater with high COD value (18 050 mg l⁻¹) for BC production by ...Gluconacetobacter xylinus was evaluated. After 7 days of fermentation, the highest BC yield (1·34 g l⁻¹) was obtained. The carbon sources including sugars (glucose and xylose), organic acids (acetic acid and butyric acid) and alcohol compounds (ethanol and butanol) were utilized by G. xylinus simultaneously during fermentation. Although the COD decrease ratio (about 14·7%) was low, the highest BC yield on COD consumption (56·2%, g g⁻¹) was relatively high and the remaining wastewater could be used for further BC fermentation. Besides, the environment of ABE fermentation wastewater showed small influence on the BC structure by comparison with the BC products obtained in traditional HS medium using field emission scanning electron microscope (FE‐SEM), Fourier transform infrared spectroscopy (FTIR) and X‐ray diffraction (XRD). Overall, ABE fermentation wastewater is one promising substrate for BC production. SIGNIFICANCE AND IMPACT OF THE STUDY: The possibility of using acetone‐butanol‐ethanol (ABE) fermentation wastewater for bacterial cellulose (BC) production by Gluconacetobacter xylinus was evaluated in this study. This is the first time that ABE fermentation wastewater was used as substrate for BC fermentation. The results provide detail information of metabolism of G. xylinus in ABE fermentation wastewater and the influence of wastewater environment on the structure of BC samples. Overall, this bioconversion could reduce the cost of BC production greatly.
Background and purpose
Facial‐sparing scapular myopathy (SHD) is the most common atypical form of facioscapulohumeral muscular dystrophy (FSHD), clinically defined as without apparent facial muscle ...weakness on neurological examination. The clinical profiles and genetic features of SHD are limited.
Methods
A cohort of 21 Chinese patients with SHD were confirmed by molecular genetic analysis based on pulsed‐field gel electrophoresis. The clinical assessments and methylation analysis were noted.
Results
The patients had FSHD‐related EcoRI fragments with 4qA haplotype ranging from 18 kb to 33 kb (mean 26.3 ± 4.6 kb). The mean onset age was 25.52 ± 8.3 years. Over half of the patients had scapular winging and asymmetry weakness consistent with FSHD, without facial symptoms during their visit. Their facial electromyogram results were almost normal or mild myogenic damage, as well as the myopathology and serum creatine kinase. A conflict was unexpectedly found in intergenerational DR1 methylation analysis.
Conclusion
Facial‐sparing scapular myopathy is characterized as mild myopathic symptoms and chronic progression of weakness. The diagnosis should be accurately confirmed through FSHD‐sized fragment detection and 4qA/B variant determination. Although the next generations of SHD had more severe muscular symptoms, local hypomethylation within D4Z4 was not found as a modifier for clinical heterogeneity.
The introduction of the Simian virus 40 (SV40) early region, the telomerase catalytic subunit (hTERT) and an oncogenic allele of H-Ras directly transforms primary human cells. SV40 small T antigen ...(ST), which forms a complex with protein phosphatase 2A (PP2A) and inhibits PP2A activity, is believed to have a critical role in the malignant transformation of human cells. Recent evidence has shown that aberrant microRNA (miRNA) expression patterns are correlated with cancer development. Here, we identified miR-27a as a differentially expressed miRNA in SV40 ST-expressing cells. miR-27a is upregulated in SV40 ST-transformed human bronchial epithelial cells (HBERST). Suppression of miR-27a expression in HBERST cells or lung cancer cell lines (NCI-H226 and SK-MES-1) that exhibited high levels of miR-27a expression lead to cell growth arrested in the G(0)-G(1) phase. In addition, suppression of miR-27a in HBERST cells attenuated the capacity of such cells to grow in an anchorage-independent manner. We also found that suppression of the PP2A B56γ expression resulted in upregulation of miR-27a similar to that achieved by the introduction of ST, indicating that dysregulation of miR-27a expression in ST-expressing cells was mediated by the ST-PP2A interaction. Moreover, we discovered that Fbxw7 gene encoding F-box/WD repeat-containing protein 7 was a potential miR-27a target validated by dual-luciferase reporter system analysis. The inverse correlation between miR-27a expression levels and Fbxw7 protein expression was further confirmed in both cell models and human tumor samples. Fbxw7 regulates cell-cycle progression through the ubiquitin-dependent proteolysis of a set of substrates, including c-Myc, c-Jun, cyclin E1 and Notch 1. Thus, promotion of cell growth arising from the suppression of Fbxw7 by miR-27a overexpression might be responsible for the viral oncoprotein ST-induced malignant transformation. These observations demonstrate that miR-27a functions as an oncogene in human tumorigenesis.
Resting-state functional MR imaging has been used for motor mapping in presurgical planning but never used intraoperatively. This study aimed to investigate the feasibility of applying intraoperative ...resting-state functional MR imaging for the safe resection of gliomas using real-time motor cortex mapping during an operation.
Using interventional MR imaging, we conducted preoperative and intraoperative resting-state intrinsic functional connectivity analyses of the motor cortex in 30 patients with brain tumors. Factors that may influence intraoperative imaging quality, including anesthesia type (general or awake anesthesia) and tumor cavity (filled with normal saline or not), were studied to investigate image quality. Additionally, direct cortical stimulation was used to validate the accuracy of intraoperative resting-state fMRI in mapping the motor cortex.
Preoperative and intraoperative resting-state fMRI scans were acquired for all patients. Fourteen patients who successfully completed both sufficient intraoperative resting-state fMRI and direct cortical stimulation were used for further analysis of sensitivity and specificity. Compared with those subjected to direct cortical stimulation, the sensitivity and specificity of intraoperative resting-state fMRI in localizing the motor area were 61.7% and 93.7%, respectively. The image quality of intraoperative resting-state fMRI was better when the tumor cavity was filled with normal saline (
= .049). However, no significant difference between the anesthesia types was observed (
= .102).
This study demonstrates the feasibility of using intraoperative resting-state fMRI for real-time localization of functional areas during a neurologic operation. The findings suggest that using intraoperative resting-state fMRI can avoid the risk of intraoperative seizures due to direct cortical stimulation and may provide neurosurgeons with valuable information to facilitate the safe resection of gliomas.
Abstract
The BOUT++ transport code is run to study the effects of plasma drifts on the divertor out-in asymmetries (DOIAs) of particle and heat fluxes and their decay widths for EAST lower single ...null H-mode discharges. The diamagnetic drift seems to have no effects on the DOIAs of total particle and heat fluxes due to its divergence-free nature. However, it could significantly increase the DOIAs of peak particle and heat fluxes and the flux decay widths. The E × B drift is found to induce a large plasma flow to the divertor region, enhancing the DOIAs of both total and peak particle and heat fluxes and the flux decay widths. Both the radial and poloidal components of the E × B drift are necessary in increasing the DOIAs, however, the radial E × B drift seems to play a more important role. The effects on the DOIAs caused by both diamagnetic and E × B drifts are reversed with the reverse of toroidal magnetic field. The heat flux decay width
λ
q
and spreading width
S
q
are important physical and engineering parameters for the divertors and could be obtained by fitting the heat flux profiles at divertor targets. The
λ
q
at the outer target from the simulation case with all drifts could well match with the multi-machine scaling proposed by Eich and the DOIA of
λ
q
is in reasonable agreement with the scaling proposed by Goldston.
Members of the genus Aeromonas are opportunistic pathogen of a variety of aquatic animals that exhibits multidrug resistance, phenotypes, virulence genes and virulence. The present study described ...the species distribution and the potential pathogenicity of Aeromonas isolated from healthy Northern snakehead (Channa argus) in China. Molecular identification revealed that A. veronii biovar veronii (69/167; 41·3%) and A. hydrophila (41/167; 24·6%) were the most common species found in Northern snakehead intestine based on sequencing of the 16S rRNA gene and DNA gyrase subunit B protein. The distribution of seven virulence factors including aer (84·4%), act (80·8%), ser (40·1%), Aha (27·5%), lip (23·4%), exu (15·0%) and LuxS (12·6%) were determined exclusively in Aeromonas isolates. All the seven virulence genes were present in 9·6% (16/167), among which 11 strains were identified as A. veronii biovar veronii. For the strains harbouring seven virulence genes, the 50% lethal doses (LD50) of isolates were lower compared to the isolates carrying two virulence genes. The challenge tests revealed that isolate W31 had the lowest lethal dose, causing 50% mortality at 4·5 × 103 colony‐forming units (CFU) per ml. Furthermore, histopathology of Northern snakehead infected with Aeromonas strains showed necrosis and congestion in liver, spleen and kidney and also damage to the intestine. This study confirms that the Aeromonas strains isolated from healthy Northern snakehead may be a cause of concern for public health.
Significance and Impact of the Study
Aeromonas species are widely distributed in aquatic environments and have considerable virulence potential. The aim of this study was to identify Aeromonas strains isolated from healthy Northern snakehead, and to investigate if Aeromonas species isolated from healthy fish potential pathogenicity with special reference to virulence and epidemiology studies.
Significance and Impact of the Study: Aeromonas species are widely distributed in aquatic environments and have considerable virulence potential. The aim of this study was to identify Aeromonas strains isolated from healthy Northern snakehead, and to investigate if Aeromonas species isolated from healthy fish potential pathogenicity with special reference to virulence and epidemiology studies.
Highly pathogenic avian influenza (HPAI) is continuously causing significant economic losses with massive poultry depopulations. Airborne transmission of HPAI was suspected, as initial bird ...mortalities were reported near air inlets of poultry houses. In addition, infected farms were distant, indicating that the viruses carried by dust particles might help the viruses travel for long distances in the environment. The objective of this study focused on simulating the airborne transmission of HPAI by using computational modeling to assess the risk of airborne and deposited avian influenza (AI) carried by poultry-litter dust particles. The Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) modeling was used in this study. Data from 168 infected cases in the Mid-Western area of U.S. were obtained from the Animal and Plant Health Inspection Service (APHIS) and Watt Poultry. The concentration simulation modeling was performed to estimate the airborne and deposited AI concentration carried by PM2.5 dust particles. Results showed that concentrations of airborne AI, deposited AI, and combined AI transmitted to other farms in a day were lower than the minimal infective dose for poultry. In most of the scenarios, the predicted probability of infection showed that Iowa-infected farms and turkey poultry houses had the highest infection probability. The findings may provide an understanding of the risk of airborne HPAI virus carried by dust particles and suggest the factors that influence long-distance airborne transmission.
Summary
Long‐term prognosis varies widely among patients with hepatitis B virus (HBV)‐related liver cirrhosis. Our study aimed to investigate the applicability of albumin‐bilirubin (ALBI), Child‐Pugh ...and model for end‐stage liver disease (MELD) scores to the long‐term prognosis prediction of HBV‐related cirrhosis. Patients diagnosed with HBV‐associated cirrhosis from the First Affiliated Hospital of Wenzhou Medical University between January 2010 and December 2015 were enrolled in this study. The patients were followed up every 3 months. The prognostic performance of ALBI in long‐term outcome prediction for HBV‐related cirrhosis was compared with Child‐Pugh and MELD scores using time‐dependent receiver operating characteristic curve (tdROC) and decision curve analysis. A total of 806 patients were included in our study with 275 (34.1%) deceased during the follow‐up. Multivariate Cox regression analysis showed that ALBI grade was an independent predictor associated with mortality. The tdROC analysis showed that ALBI score (0.787, 0.830 and 0.833) was superior to MELD (0.693, P=.003; 0.717, P<.001; 0.744, P<.001) and Child‐Pugh score (0.641, P<.001; 0.649, P<.001; 0.657, P<.001) for predicting 1‐year, 2‐year and 3‐year mortality. Additionally, decision curves also got the similar results. In addition, patients with lower ALBI score had a longer life expectancy, even among patients within the same Child‐Pugh class. Thus, ALBI score was effective in predicting the long‐term prognosis for patients with HBV‐related cirrhosis and more accurate than Child‐Pugh and MELD scores.
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