Identification of new molecular targets for the treatment of endometrial cancer (EC) is an important clinical goal, especially for the patients which were resistant to conventional therapies. The ...aryl hydrocarbon receptor (AhR) is a ligand- activated transcription factor known primarily as the mediator of dioxin toxicity. However, the AhR can also inhibit cellular proliferation in a ligand-dependent manner and act as a tumor suppressor in mice, thus may be a potential anticancer target. In this study, we investigated if the endogenous AhR ligand 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) regulated proliferation and migration of EC cells via AhR.
We used quantitative real-time PCR and western blot to assess the expression of AhR in EC tissues and paired adjacent normal tissues. In addition, we conducted transwell assay to test whether the treatment of ITE altered the locomotive potential and proliferation of EC cells. Next, we conducted mouse xenograft models to further explore the in vivo effect of ITE.
We found that the AhR protein and RNA levels were increased mildly in EC tissues relative to the para-tumor normal endometrial tissues. Besides, ITE suppressed EC cells proliferation and migration in vitro, and also suppressed EC cells xenograft growth in mice.
Our results strongly supported the possibility of using the ITE as a small molecular compound for the treatment of EC.
Low-cost and efficient activated carbon (AC) was prepared from Typha orientalis via phosphoric acid activation for chloramphenicol (CAP) removal. The adsorption capacity and mechanisms of CAP on AC ...were investigated. The physicochemical properties of AC were characterized by an N2 adsorption/desorption isotherm, elemental analysis, Boehm’s titration and X-ray photoelectron spectroscopy (XPS). The effects of experimental parameters were investigated to study the adsorption behaviors of CAP on AC, including contact time, initial concentration, ionic strength, and initial pH. AC had a micro-mesoporous structure with a relatively large surface area (794.8 m2/g). The respective contents of acidic and basic functional groups on AC were 2.078 and 0.995 mmol/g. The adsorption kinetic that was well described by a pseudo-second-order rate model implied a chemical controlling step. The adsorption isotherm was well fitted with the Freundlich isotherm model, and the maximum CAP adsorption capacity was 0.424 mmol/g. The ionic strength and pH had minimal effects on CAP adsorption. The dominant CAP adsorption mechanisms on AC were evaluated and attributed to π-π electron-donor-acceptor (EDA) interaction, hydrophobic interaction, in conjunction with hydrogen-bonding interaction. Additionally, AC exhibited an efficient adsorption performance of CAP in a realistic water environment.
A more general narrowband regular-shaped geometry-based statistical model (RS-GBSM) combined with the line of sight (LoS) and single bounce (SB) rays for unmanned aerial vehicle (UAV) multiple-input ...multiple-output (MIMO) channel is proposed in this paper. The channel characteristics, including space-time correlation function (STCF), Doppler power spectral density (DPSD), level crossing rate (LCR) and average fade duration (AFD), are derived based on the single sphere reference model for a non-isotropic environment. The corresponding sum-of-sinusoids (SoS) simulation models including both the deterministic model and statistical model with finite scatterers are also proposed for practicable implementation. The simulation results illustrate that the simulation models well reproduce the channel characteristics of the single sphere reference model with sufficient simulation scatterers. And the statistical model has a better approximation of the reference model in comparison with the deterministic one when the simulation trials of the stochastic model are sufficient. The effects of the parameters such as flight height, moving direction and Rice factor on the characteristics are also studied.
Purpose
Glutamate weighted Chemical Exchange Saturation Transfer (GluCEST) MRI is a noninvasive technique for mapping parenchymal glutamate in the brain. Because of the sensitivity to field (B0) ...inhomogeneity, the total acquisition time is prolonged due to the repeated image acquisitions at several saturation offset frequencies, which can cause practical issues such as increased sensitivity to patient motions. Because GluCEST signal is derived from the small z‐spectrum difference, it often has a low signal‐to‐noise‐ratio (SNR). We proposed a novel deep learning (DL)‐based algorithm armed with wide activation neural network blocks to address both issues.
Methods
B0 correction based on reduced saturation offset acquisitions was performed for the positive and negative sides of the z‐spectrum separately. For each side, a separate deep residual network was trained to learn the nonlinear mapping from few CEST‐weighted images acquired at different ppm values to the one at 3 ppm (where GluCEST peaks) in the same side of the z‐spectrum.
Results
All DL‐based methods outperformed the “traditional” method visually and quantitatively. The wide activation blocks‐based method showed the highest performance in terms of Structural Similarity Index (SSIM) and peak signal‐to‐noise ratio (PSNR), which were 0.84 and 25dB respectively. SNR increases in regions of interest were over 8dB.
Conclusion
We demonstrated that the new DL‐based method can reduce the entire GluCEST imaging time by ˜50% and yield higher SNR than current state‐of‐the‐art.
Eastern North America records a tectonic history of over 3 Ga in duration. Much of this record is preserved within the lithosphere and may be unraveled by detailed studies of its interior structure. ...Past episodes of tectonic activity likely left their imprints in the form of anisotropy‐forming rock fabric presently preserved in the lithosphere of the continent. We perform shear wave splitting measurements using observations of core‐refracted waves collected from a ~1,300‐km‐long array extending from James Bay in Quebec to the Fundy basin in Maine, with lateral spacing of 10–100 km between instruments. Close spacing of instruments helps us associate anisotropic properties with geological boundaries. We find that the fast polarizations concentrate between N60°E and N90°E with an average of N80°E and change systematically with backazimuth. In addition, we observe a lateral increase in delay time from 0.56 ±0.25 s at the NW end of the array to 0.90 ± 0.41 s at the SE end. The location of lateral change in delay time does not match geological boundaries on the surface but seems to match the geophysical boundary at depth of 160 km. We interpret this boundary in splitting values to be the edge of cratonic lithosphere at depth. Our observations suggest that the anisotropic structure beneath our study area is complex and possibly both multilayered and laterally variable.
Key Points
We made consistent shear wave splitting measurements from 24 earthquakes along a 1,300‐km‐long transect in eastern North America
Fast polarizations vary systematically with backazimuth, while delay times increase from the center of the continent to the coast
We interpret the anisotropic structure to be multilayered, and propose that the lateral change in delay time marks the edge of the craton at depth
The gut-uterus axis plays a pivotal role in the pathogenesis of endometrial cancer (EC). However, the correlations between the endometrial microbiome and endometrial tumor transcriptome in patients ...with EC and the impact of the endometrial microbiota on hematological indicators have not been thoroughly clarified. In this prospective study, endometrial tissue samples collected from EC patients (n = 30) and healthy volunteers (n = 10) were subjected to 16S rRNA sequencing of the microbiome. The 30 paired tumor and adjacent nontumor endometrial tissues from the EC group were subjected to RNAseq. We found that
Pelomonas
and
Prevotella
were enriched in the EC group with a high tumor burden. By integrating the microbiome and hematological indicators, a correlation was observed between
Prevotella
and elevated serum D-dimer (DD) and fibrin degradation products (FDPs). Further transcriptome analysis identified 8 robust associations between
Prevotella
and fibrin degradation-related genes expressed within ECs. Finally, the microbial marker of
Prevotella
along with DD and FDPs showed a high potential to predict the onset of EC (AUC = 0.86). Our results suggest that the increasing abundance of
Prevotella
in endometrial tissue combined with high serum DD and FDP contents may be important factors associated with tumor burden. The microbe-associated transcripts of host tumors can partly explain how
Prevotella
promotes DD and FDPs.
The genus Acidithiobacillus has been widely concerned due to its superior survival and oxidation ability in acid mine drainage (AMD). However, the contribution of insertion sequence (IS) to their ...biological evolution and environmental adaptation is very limited. ISs are the simplest kinds of mobile genetic elements (MGEs), capable of interrupting genes, operons, or regulating the expression of genes through transposition activity. ISs could be classified into different families with their own members, possessing different copies.
In this study, the distribution and evolution of ISs, as well as the functions of the genes around ISs in 36 Acidithiobacillus genomes, were analyzed. The results showed that 248 members belonging to 23 IS families with a total of 10,652 copies were identified within the target genomes. The IS families and copy numbers among each species were significantly different, indicating that the IS distribution of Acidithiobacillus were not even. A. ferrooxidans had 166 IS members, which may develop more gene transposition strategies compared with other Acidithiobacillus spp. What's more, A. thiooxidans harbored the most IS copies, suggesting that their ISs were the most active and more likely to transpose. The ISs clustered in the phylogenetic tree approximately according to the family, which were mostly different from the evolutionary trends of their host genomes. Thus, it was suggested that the recent activity of ISs of Acidithiobacillus was not only determined by their genetic characteristics, but related with the environmental pressure. In addition, many ISs especially Tn3 and IS110 families were inserted around the regions whose functions were As/Hg/Cu/Co/Zn/Cd translocation and sulfur oxidation, implying that ISs could improve the adaptive capacities of Acidithiobacillus to the extremely acidic environment by enhancing their resistance to heavy metals and utilization of sulfur.
This study provided the genomic evidence for the contribution of IS to evolution and adaptation of Acidithiobacillus, opening novel sights into the genome plasticity of those acidophiles.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Ecological restoration (ER) programs play an important role in local and global climate change and carbon management policy interventions. Water resource is a key criterion for assessing the ...sustainability of ERs. Herein, we explored the spatiotemporal patterns of rainfall interception (RI, an important component of ecosystem water budgets), and its drivers after ER implementation in China. Further, we assessed whether ERs are sustainable by analyzing the trends of RI and water supply. As expected, we found that ERs caused an increase in RI in China from 2001 to 2018 (0.64 mm yr
−1
,
p
< 0.01). Changes in the normalized difference vegetation index and leaf area index contributed to a higher change in RI compared with other drivers. The decrease in RI was mainly recorded in the Qinghai–Tibet Plateau in Southwest, northern North, and southern Central and Southern China. Conversely, an increasing trend of RI was recorded in the Loess Plateau in Northwest, Northeast, and East China. Moreover, ERs are not always unsustainable in China, especially in Northeast, East, Central and Southern, and high-latitude regions of northern North China. Even in the Loess Plateau, which was criticized by previous studies, the unsustainability occurred only in the semi-humid region. Future ERs should be prioritized in southern parts of Eastern, Central, and Southern China, and must be appropriately considered in the Northeast and high-latitude regions in North China. It should be alert to the pressures of ERs on water supply, and its demand remains vigilant in the Qinghai–Tibet Plateau and semihumid areas of the Loess Plateau. This study provides new ideas for accurately evaluating the impact of ERs on water security and the sustainability of ERs.
Strain-stiffening properties derived from biological tissue have been widely observed in biological hydrogels and are essential in mimicking natural tissues. Although strain-stiffening has been ...studied in various protein-based hydrogels, effective approaches for tuning the strain-stiffening properties of protein hydrogels have rarely been explored. Here, we demonstrated a new method to tune the strain-stiffening amplitudes of protein hydrogels. By adjusting the surface charge of proteins inside the hydrogel using negatively/positively charged molecules, the strain-stiffening amplitudes could be quantitively regulated. The strain-stiffening of the protein hydrogels could even be enhanced 5-fold under high deformations, while the bulk property, recovery ability and biocompatibility remained almost unchanged. The tuning of strain-stiffening amplitudes using different molecules or in different protein hydrogels was further proved to be feasible. We anticipate that surface charge adjustment of proteins in hydrogels represents a general principle to tune the strain-stiffening property and can find wide applications in regulating the mechanical behaviors of protein-based hydrogels.
The morbidity and mortality of endometrial tumors, a common type of malignant cancer in women, have increased in recent years. POLE encodes the DNA polymerase ε, which is responsible for the leading ...strand DNA replication. Somatic mutations of POLE have been acknowledged in numerous cancers, resulting in the accumulation of DNA errors, leading to ultra-mutated tumors. Mutations in the exonuclease domain of POLE have been reported to improve progression-free survival in endometrial cancer. However, the potential relationship and underlying mechanism between POLE mutations and the prognosis of endometrial cancer patients remains unclear.
The whole exome sequencing data, RNA sequencing data, and clinical information were obtained from the TCGA database and employed for the analyses in this study. The detailed mutational information was analyzed using whole exome sequencing data and the mutated genes were shown with OncoPlot. The survival curves and cox proportional hazards regression analysis were used to accessed patient prognosis, the association of clinical characteristics and prognosis. Differentially expressed genes were analyzed by the edgeR R/Bioconductor package, then the GSEA Pre-ranked tool was used for Gene Set Enrichment Analysis (GSEA) to estimate the function of genes. Expression values were clustered using hierarchical clustering with Euclidean distance and ward linkage by the dendextend R package.
POLE mutational status was proven to be an independent prognostic factor for endometrial cancer patients. Patients with somatic POLE mutations presented a favorable prognosis. POLE mutations regulated glycolysis and cytokine secretion, affecting cell metabolism and immune response. Autocrine motility factor (AMF)/PGI and AMFR/gp78 exhibited higher expression levels in POLE mutant patients. The comprehensive high expressions of AMFR/gp78 and low expression of POLE were associated with the favorable prognosis of endometrial cancer patients.
This study showed the POLE mutations a vital factor in endometrial cancer patients, leading to a higher expression of AMF/PGI and AMFR/gp78. These results suggested comprehensive consideration of the POLE mutations, expression of AMF/PGI and AMFR/gp78 may provide a more feasible and effective approach for the treatment of endometrial cancer, which might improve the prognosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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