Spheroidal cancer cell cultures have been used to enrich cancer stem cells (CSC), which are thought to contribute to important clinical features of tumors. This study aimed to map the regulatory ...networks driven by circular RNAs (circRNAs) in CSC-enriched colorectal cancer (CRC) spheroid cells. The spheroid cells established from two CRC cell lines acquired stemness properties in pluripotency gene expression and multi-lineage differentiation capacity. Genome-wide sequencing identified 1503 and 636 circRNAs specific to the CRC parental and spheroid cells, respectively. In the CRC spheroids, algorithmic analyses unveiled a core network of mRNAs involved in modulating stemness-associated signaling pathways, driven by a circRNA-microRNA (miRNA)-mRNA axis. The two major circRNAs, hsa_circ_0066631 and hsa_circ_0082096, in this network were significantly up-regulated in expression levels in the spheroid cells. The two circRNAs were predicted to target and were experimentally shown to down-regulate miR-140-3p, miR-224, miR-382, miR-548c-3p and miR-579, confirming circRNA sponging of the targeted miRNAs. Furthermore, the affected miRNAs were demonstrated to inhibit degradation of six mRNA targets, viz. ACVR1C/ALK7, FZD3, IL6ST/GP130, SKIL/SNON, SMAD2 and WNT5, in the CRC spheroid cells. These mRNAs encode proteins that are reported to variously regulate the GP130/Stat, Activin/Nodal, TGF-β/SMAD or Wnt/β-catenin signaling pathways in controlling various aspects of CSC stemness. Using the CRC spheroid cell model, the novel circRNA-miRNA-mRNA axis mapped in this work forms the foundation for the elucidation of the molecular mechanisms of the complex cellular and biochemical processes that determine CSC stemness properties of cancer cells, and possibly for designing therapeutic strategies for CRC treatment by targeting CSC.
Meat quality and nutritional value hinge on many factors, including fat content in the adipose tissue. In the adipogenesis process, stem cells are first committed to become preadipocytes, followed by ...preadipocyte differentiation. In the later event, peroxisome proliferator activated receptor gamma (PPARγ) is the gateway through which adipogenic genes are activated. This review focuses on clarifying the effects of signaling transduction on PPARγ that have been experimentally established in the adipogenesis process. Furthermore, microRNA (miRNA) are validated to target the signaling factors and impact adipogenesis are appraised to establish the miRNA-signaling-PPARγ regulatory connection in adipogenesis. As opposed to red meat, chicken is white meat, which is increasingly appreciated for health and environmental reasons. Most works reported on the miRNA-signaling-PPARγ network in adipogenesis used human and other laboratory and farm animal models. We show here that database interrogation and bioinformatics analysis may be applied to extrapolate reported findings to chicken based on evolutionary conservation. Understanding molecular modulation of adipogenesis may contribute to clinical treatment of lipid disorders and obesity in humans, and improved meat quality and commercial value in chicken farming, and possibly in the creation of artificial meat.
Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30–50 million individuals and clinical hallmarks of AMD are observed in at least one ...third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 2011; Klein et al., 2011). Preventive interventions through dietary modulation are attractive strategies because many studies suggest a benefit of micro- and macronutrients with respect to AMD, as well as other age-related debilities, and with few, if any, adverse effects (Chiu, 2011). Preservation of vision would enhance quality of life for millions of elderly people, and alleviate the personal and public health financial burden of AMD (Frick et al., 2007; Wood et al., 2011). Observational studies indicate that maintaining adequate levels of omega-3 fatty acids (i.e. with 2 servings/week of fish) or a low glycemic index diet may be particularly beneficial for early AMD and that higher levels of carotenoids may be protective, most probably, against neovascular AMD. Intervention trials are needed to better understand the full effect of these nutrients and/or combinations of nutrients on retinal health. Analyses that describe effects of a nutrient on onset and/or progress of AMD are valuable because they indicate the value of a nutrient to arrest AMD at the early stages. This comprehensive summary provides essential information about the value of nutrients with regard to diminishing risk for onset or progress of AMD and can serve as a guide until data from ongoing intervention trials are available.
The purpose of this research was to investigate the effects of a computer-assisted concept mapping learning strategy on EFL college learners’ English reading comprehension. The research questions ...were: (1) what was the influence of the computer-assisted concept mapping learning strategy on different learners’ English reading comprehension? (2) did the computer-assisted concept mapping learning strategy affect learners’ use of other English reading strategies? One hundred ninety-four freshmen who were enrolled in the English course were divided into low-level and high-level groups according to their English proficiency. A computer-assisted concept mapping learning strategy was introduced to the learners in the experimental class to improve their reading ability. Through two-way ANOVA analysis, it was found that the computer-assisted concept mapping learning strategy had greater reading benefit for the low-level group than for the high-level group. In addition, the results of independent sample
t-test analysis indicated that the computer-assisted concept mapping learning strategy enhanced learners’ use of other English reading strategies–listing, enforcing, and reviewing.
Cell composition deconvolution (CCD) is a type of bioinformatic task to estimate the cell fractions from bulk gene expression profiles, such as RNA-seq. Many CCD models were developed to perform ...linear regression analysis using reference gene expression signatures of distinct cell types. Reference gene expression signatures could be generated from cell-specific gene expression profiles, such as scRNA-seq. However, the batch effects and dropout events frequently observed across scRNA-seq datasets have limited the performances of CCD methods. We developed a deep neural network (DNN) model, HASCAD, to predict the cell fractions of up to 15 immune cell types. HASCAD was trained using the bulk RNA-seq simulated from three scRNA-seq datasets that have been normalized by using a Harmony-Symphony based strategy. Mean square error and Pearson correlation coefficient were used to compare the performance of HASCAD with those of other widely used CCD methods. Two types of datasets, including a set of simulated bulk RNA-seq, and three human PBMC RNA-seq datasets, were arranged to conduct the benchmarks. HASCAD is useful for the investigation of the impacts of immune cell heterogeneity on the therapeutic effects of immune checkpoint inhibitors, since the target cell types include the ones known to play a role in anti-tumor immunity, such as three subtypes of CD8 T cells and three subtypes of CD4 T cells. We found that the removal of batch effects in the reference scRNA-seq datasets could benefit the task of CCD. Our benchmarks showed that HASCAD is more suitable for analyzing bulk RNA-seq data, compared with the two widely used CCD methods, CIBERSORTx and quanTIseq. We applied HASCAD to analyze the liver cancer samples of TCGA-LIHC, and found that there were significant associations of the predicted abundance of Treg and effector CD8 T cell with patients' overall survival. HASCAD could predict the cell composition of the PBMC bulk RNA-seq and classify the cell type from pure bulk RNA-seq. The model of HASCAD is available at https://github.com/holiday01/HASCAD.
Purpose We hypothesized that major American dietary patterns are associated with risk for age-related macular degeneration (AMD). Design Cross-sectional study. Methods We classified 8103 eyes in 4088 ...eligible participants in the baseline Age-Related Eye Disease Study (AREDS). They were classified into control (n = 2739), early AMD (n = 4599), and advanced AMD (n = 765) by the AREDS AMD Classification System. Food consumption data were collected by using a 90-item food frequency questionnaire. Results Two major dietary patterns were identified by factor (principal component) analysis based on 37 food groups and named Oriental and Western patterns. The Oriental pattern was characterized by higher intake of vegetables, legumes, fruit, whole grains, tomatoes, and seafood. The Western pattern was characterized by higher intake of red meat, processed meat, high-fat dairy products, French fries, refined grains, and eggs. We ranked our participants according to how closely their diets line up with the 2 patterns by calculating the 2 factor scores for each participant. For early AMD, multivariate-adjusted odds ratio (OR) from generalized estimating equation logistic analysis comparing the highest to lowest quintile of the Oriental pattern score was ORE5O = 0.74 (95% confidence interval (CI): 0.59–0.91; Ptrend =0.01), and the OR comparing the highest to lowest quintile of the Western pattern score was ORE5W = 1.56 (1.18–2.06; Ptrend = 0.01). For advanced AMD, the ORA5O was 0.38 (0.27–0.54; Ptrend < 0.0001), and the ORA5W was 3.70 (2.31–5.92; Ptrend < 0.0001). Conclusions Our data indicate that overall diet is significantly associated with the odds of AMD and that dietary management as an AMD prevention strategy warrants further study.
Cardiac valve calcification (CVC), characterized by the accumulation of calcium in the heart valves, is highly prevalent among patients undergoing dialysis. This meta-analysis aimed to provide an ...updated summary of recent studies on the prognostic value of CVC in patients undergoing dialysis. We conducted a search of PubMed, Embase, and Web of Science to identify observational studies investigating cardiovascular or all-cause mortality associated with CVC in dialysis patients until March 2023. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated for the meta-analysis, and the strength and significance of the associations between CVC and mortality outcomes in dialysis patients were assessed. From 6218 initially identified studies, we included 10 critical studies with a total of 3376 dialysis patients in a further meta-analysis. Pooled analyses demonstrated a significant association between CVC and an elevated risk of all-cause and cardiovascular mortality in dialysis patients. In our study, we discovered HRs of 1.592 (95% CI 1.410-1.797) for all-cause mortality and 2.444 (95% CI 1.632-3.659) for cardiovascular mortality. Furthermore, subgroup analysis revealed elevated all-cause mortality among patients with mitral valve calcification (HR 1.572; 95% CI 1.200-2.060) compared to those with aortic valve calcification (HR 1.456; 95% CI 1.105-1.917). Similarly, patients undergoing peritoneal dialysis faced a greater risk for all-cause mortality (HR 2.094; 95% CI 1.374-3.191) than those on hemodialysis (HR 1.553; 95% CI 1.369-1.763). This highlights the possibility of CVC being an independent risk factor for dialysis patients, particularly in relation to mitral valve calcification or peritoneal dialysis.
An enantioselective synthesis of 1‐substituted tetrahydroisoquinolines from L–Dopa methyl ester through intramolecular aryl radical cyclization is demonstrated. The strategy consists of bromination ...of (S)‐2‐amino‐3‐(2‐bromo‐4,5‐dimethoxyphenyl)propanoate followed by condensation with various aldehydes to afford bromoimidate ester. Aryl radicals generated from bromoimidate ester under the radical generating conditions (nBu3SnH/AIBN) cyclizes via 6‐endo mode to afford cis‐1‐substituted tetrahydroisoquinolines exclusively in 99% ee. The utility of this synthetic protocol is demonstrated in the synthesis of (6S, 12aS) Tadalafil (5 steps, 21%, 99% ee).
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