Mosleysumner7844

In particular, in the existing models, Uranus and Neptune are assumed to have identical composition, nearly identical pressure-temperature profiles, and a single convecting middle layer ("mantle") made of a mixture of H2O/CH4/NH3 in the ratio of 56.532.511. Here, we provide new insights, shedding light into the difference of heat flows from Uranus and Neptune, which require them to have different compositions, pressure-temperature conditions, and a more complex internal structure.Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), a novel brominated flame retardant, can potentially cause lipid metabolism disorder; however, its biological effects on lipid homeostasis remain unknown. We investigated its ability to cause nonalcoholic fatty liver disease (NAFLD) in zebrafish. Female zebrafish were fed a high-fat diet (HFD, 24% crude fat) or normal diet (ND, 6% crude fat), and exposed to TBPH (0.02, 2.0 μM) for 2 weeks. Consequently, HFD-fed fish showed a higher measured concentration of TBPH than ND-fed fish. Further, TBPH-treated fish in the HFD group showed higher hepatic triglyceride levels and steatosis. In comparison to ND-fed fish, treating HFD-fed fish with TBPH led to an increase in the concentration of several proinflammatory markers (e.g., TNF-α, IL-6); TBPH exposure also caused oxidative stress. In addition, the mRNA levels of genes encoding peroxisome proliferator-activated receptors were increased, and the transcription of genes involved in lipid synthesis, transport, and oxidation was upregulated in both ND- and HFD-fed fish. Both the ND and HFD groups also showed demethylation of the peroxisome proliferator-activated receptor-γ coactivator 1-α gene promoter, accompanied by the upregulation of tet1 and tet2 transcription. To summarize, we found that TBPH amplified the disruption of lipid homeostasis in zebrafish, leading to the enhancement of diet-induced NAFLD progression.APOBEC3A (A3A) is a cytidine deaminase involved in innate immune response and is able to catalyze deamination on both DNA and RNA substrates. It was used in creating the CRISPR-mediated base editor, but has since been held back due to its dual activities. On the other hand, it has been a challenge to separate A3A's dual activities in order to enable it for single-base RNA editors. Here we developed the reporter system for C-to-U RNA editing and employed rational design for mutagenesis to differentiate deaminase activities on RNA and DNA substrates to obtain an RNA-specific editase. Generation and examination of 23 previous A3A mutants showed their deamination activity on RNA was mostly abolished when their activity on DNA was impaired, with the exception of mutant N57Q that displayed an inverse change. We designed new mutations on Loops 1 and 7 based on A3A's crystal structure and found mutants H29R and Y132G had differential effects on catalytic activity on RNA and DNA substrates. In order to engineer an A3A with RNA-specific deaminase activity, we combined Y132G with mutations in Loop 1 or helix 6 by rational design. Two multipoint mutants, Y132G/K30R and Y132G/G188A/R189A/L190A, were successful in retaining high deaminase activity on RNA substrate while eliminating deaminase activity on DNA. We, for the first time, created novel human A3A variants with RNA-specific cytidine deaminase activity, providing insight into A3A's mechanism on substrate recognition and a new addition of a toolset to the creation of a RNA-specific C-to-U base editor.

This study aimed to investigate the clinical characteristics of acute myeloid leukemia with myelodysplasia-related-changes (AML-MRC) according to the 2016 WHO classification and the preferred therapy of patients with AML-MRC and aged 60-75 years.

We retrospectively analyzed the differences of clinical data between 190 patients with AML-MRC and 667 patients with AML not otherwise specified (AML-NOS). And we compared different therapeutic regimens among patients with AML-MRC and aged 60-75 years.

Compared with AML-NOS, patients with AML-MRC had significantly different clinical characteristics as well as worse overall survival (OS) (9.2 vs 13.6 months; p<0.001) and complete remission (CR) rate (65.3% vs 76.2%; p=0.005). Gefitinib nmr Multivariate analysis performed in the whole group (patients with AML-MRC and AML-NOS) showed that AML-MRC was the independent prognostic factor (p=0.002). Additional multivariate analysis performed in 190 patients with AML-MRC indicated that age (p<0.001) and LDH (p=0.031) were independent prognostic factors. Compared with IA/DA regimen [idarubin and cytarabine (IA) or daunorubicin and cytarabine (DA)], DAC+CAG regimen [decitabine and half-dose CAG regimen (cytarabine, aclarubicin and granulocyte colony-stimulating factor)] was associated with better OS (4.5 vs 6.2 months; p=0.021) in patients aged 60-75 years and categorized into unfavorable-risk group.

AML-MRC exhibited worse clinical outcome compared with AML-NOS. Compared with IA/DA regimen, DAC+CAG regimen was the optimal choice for patients with AML-MRC in unfavorable-risk group and aged 60-75 years.

AML-MRC exhibited worse clinical outcome compared with AML-NOS. Compared with IA/DA regimen, DAC+CAG regimen was the optimal choice for patients with AML-MRC in unfavorable-risk group and aged 60-75 years.

To identify the clinical significance of

and common cytogenetic abnormalities.

114 patients with newly diagnosed MM and

3 abnormalities were selected from two large patient cohorts of collaborating hospitals from 2010 to 2017. The characteristics and outcomes of these patients were analyzed.

and other common mutations in MM patients were quantified by fluorescence in situ hybridization (FISH). Kaplan-Meier curves and Log-rank test were applied for survival analysis. Cox proportional hazard model for covariate analysis was used to determine the prognostic factors.

By extensive data analysis, we find

amplification is a strong positive predictor for complete response (CR) to therapy and positively correlated with patient survival. The number of simultaneous genomic abnormalities with

mutation has a modest impact on patient survival. Within these mutations, 1q21 amplification is associated with decreased CR (OR=4.209) and FGFR3 levels are positively correlated with patient progression-free and overall survival.