Hydrogels based on N-acryloyl-NЈ-methylpiperazine (AcrNMP) swelled extensively in solutions of low pH due to the protonation of the tertiary amine. The water transport in the gels under an acidic condition was non-Fickian and nearly Fickian in neutral pH with the collective diffusion coefficients determined as 2.08 ϫ 10 Ϫ7 and 5.00 ϫ 10 Ϫ7 cm Ϫ2 s Ϫ1 , respectively. These gels demonstrated good metal-uptake behavior with various divalent metal ions, in particular, copper and nickel, with the uptake capacity increased with increasing pH. The swelling ratio of the gel in the presence of metal ions decreased with increasing metal ion uptake. The results suggest that high metal ion uptake can lead to physical crosslinking arising from the interchain metal complex formation. The metal-loaded gels could be stripped easily with 1M H 2 SO 4 without any loss in their uptake capacity.
The prediction utility of Framingham Risk Score in populations with low conventional cardiovascular risk burden is limited, particularly among women. Gender-specific markers to predict cardiovascular risk in overtly healthy people are lacking. In this study we hypothesize that postprandial responses triggered by a high-calorie meal test differ by gender in their ability to triage asymptomatic subjects into those with and without subclinical atherosclerosis. A total of 101 healthy Chinese subjects (46 females, 55 males) at low risk of coronary heart disease completed the study. Subjects underwent cardiovascular imaging and postprandial blood phenotyping after consuming a standardized macronutrient meal. Prediction models were developed using logistic regression and subsequently subjected to cross-validation to obtain a de-optimized receiver operating characteristic (ROC) curve. Distinctive gender differences in postprandial trajectories of glucose, lipids and inflammatory markers were observed. We used gender-specific association with different combinations of postprandial predictors to develop 2 models for predicting risk of subclinical atherosclerosis in males (ROC AUC = 0.7867, 95% CI 0.6567, 0.9166) and females (ROC AUC = 0.9161, 95% CI 0.8340, 0.9982) respectively. We report novel postprandial models for predicting subclinical atherosclerosis in apparently healthy Asian subjects using a gender-specific approach, complementing the conventional Framingham Risk Score.Clinical Trial Registration: The trial was registered at clinicaltrials.gov as NCT03531879.
Non-Hodgkin’s lymphoma (NHL) is a diverse group of malignancies, encompassing the most common diffuse large B-cell lymphoma (DLBCL) to the rarer T-cell lymphomas. DDX3X is an RNA helicase and, depending on tumour type, plays tumour suppressive or oncogenic roles in cancer. However, its role in NHL is not clear. Targeted sequencing of DDX3X hotspots on exons 8-15 in a cohort of 158 unselected DLBCL subjects showed DDX3X mutations in 5 cases; whereas whole exome sequencing in a cohort of 9 relapsed/refractory DLBCL patients treated with R-CHOP identified DDX3X mutations in 4 cases. DLBCL patients (n=223) with DDX3X mutations had worse 5-year overall survival (22%) compared to patients with wild-type DDX3X (72%, p=0.021). Using DLBCL and cutaneous T-cell lymphoma (CTCL) cell lines, we showed that the expression of mutant DDX3X-R475C or DDX3X knockdown significantly enhanced cell migratory/invasive potential and elevated the phosphorylation of STAT3, Akt and p42/44. DDX3X loss increased resistance to doxorubicin and histone deacetylase targeting drugs in DLBCL and CTCL cells, respectively. Importantly, B- and T-cell lineage DDX3X-depleted cells remained sensitive to STAT3 inhibition. We conclude that DDX3X mutations are important driver lesions in NHL subtypes and are associated with chemoresistance but may be countered with a STAT3 inhibitor.
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