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Gene alterations are recognized as important events in acute myeloid leukemia (AML) progression. Studies on hematopoiesis of altered genes contribute to a better understanding on their roles in AML progression. Our previous work reported a DEAH box helicase 15 (DHX15) R222G mutation in AML patients, and we showed DHX15 overexpression is associated with poor prognosis in AML patients. In this work, we further study the role of dhx15 in zebrafish developmental hematopoiesis by generating dhx15−/− zebrafish using transcription activator‐like effector nuclease technology. Whole‐mount in situ hybridization (WISH) analysis showed hematopoietic stem/progenitor cells were dramatically perturbed when dhx15 was deleted. Immunofluorescence staining indicated inhibited hematopoietic stem/progenitor cell (HSPC) proliferation instead of accelerated apoptosis were detected in dhx15−/− zebrafish. Furthermore, our data showed that HSPC defect is mediated through the unfolded protein response (UPR) pathway. DHX15 R222G mutation, a recurrent mutation identified in AML patients, displayed a compromised function in restoring HSPC failure in dhx15−/−; Tg (hsp: DHX15 R222G) zebrafish. Collectively, this work revealed a vital role of dhx15 in the maintenance of definitive hematopoiesis in zebrafish through the unfolded protein respone pathway. The study of DHX15 and DHX15 R222G mutation could hold clinical significance for evaluating prognosis of AML patients with aberrant DHX15 expression., Dhx15 is essential for hematopoietic stem/progenitor cell (HSPC) development in zebrafish; HSPC failure is mediated by the unfolded protein response (UPR) pathway in dhx15−/− zebrafish.

Since noninvasive central blood pressure (BP) measuring devices are readily available, central BP has gained growing attention regarding its clinical application in the management of hypertension. The disagreement between central and peripheral BP has long been recognized. Some previous studies showed that noninvasive central BP may be better than the conventional brachial BP in association with target organ damages and long‐term cardiovascular outcomes. Recent studies further suggest that the central BP strategy for confirming a diagnosis of hypertension may be more cost‐effective than the conventional strategy, and guidance of hypertension management with central BP may result in less use of medications to achieve BP control. Despite the use of central BP being promising, more randomized controlled studies comparing central BP‐guided therapeutic strategies with conventional care for cardiovascular events reduction are required because noninvasive central and brachial BP measures are conveniently available. In this brief review, the rationale supporting the utility of central BP in clinical practice and relating challenges are summarized.

Aims It remains inconclusive whether the use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk of atrial fibrillation (AF), especially in middle-aged Asian populations. In this study, we evaluated the association between NSAID use and the risk of AF in a nationwide population-based study of middle-aged individuals in Taiwan. Methods A nested case-control study was conducted using the National Health Insurance Research Database (NHIRD) in Taiwan. We identified the cases with a diagnosis of AF (ICD-9-CM codes: 427.31) and the matched controls from three independent Longitudinal Health Insurance Databases (LHIDs) derived from the NHIRD from data collected from 2001 to 2013. Conditional logistic regression models with covariate adjustment were performed to evaluate the association between NSAID use and the risk of AF. Results A total of 57 058 participants (28 529 AF cases and 28 529 matched controls) were included. Participants with NSAID use had an elevated risk of AF compared to non-users [adjusted odds ratio (AOR) = 1.18, 95% confidence interval (CI): 1.14-1.23]. When further assessing the effects of different classes of NSAIDs on the risk of AF, the results showed that participants who used non-selective NSAIDs had a significantly elevated risk of AF (AOR = 1.18, 95% CI: 1.13-1.23), as did participants with a combined use of selective and non-selective NSAIDs (AOR = 1.30, 95% CI: 1.21-1.39). Conclusions NSAID use was associated with an increased risk of AF occurrence among the participants included in our study cohort. Closely monitoring the adverse effects of NSAID treatment on the risk of AF will be important, particularly among individuals at high risk.

DHX15 plays a role in leukaemogenesis and leukaemia relapse. However, the mechanism underlying the transcriptional regulation of DHX15 in ALL has not been elucidated. Our present study aimed to explore the functional promoter region of DHX15 and to investigate the transcription factors controlling the transcription of this gene. A luciferase assay performed with several truncated constructs identified a 501‐bp region as the core promoter region of DHX15. Site‐directed mutagenesis, electrophoretic mobility shift and chromatin immunoprecipitation assays showed that ETS1 and SP1 occupied the DHX15 promoter. Furthermore, knockdown of ETS1 and SP1 resulted in suppression of DHX15, whereas the overexpression of these genes led to up‐regulation of DHX15. Interestingly, in samples obtained from patients with ALL at diagnosis, both ETS1 and SP1 correlated positively with DHX15 expression. Additionally, differences in methylation of the DHX15 core promoter region were not observed between the patients and controls. In conclusion, we identified the core promoter region of DHX15 and demonstrated that ETS1 and SP1 regulated DHX15 expression in ALL.

Objectives To investigate whether dietary patterns are associated with frailty phenotypes in an elderly Taiwanese population. Design Cross-sectional. Setting Nutrition and Health Survey in Taiwan (NAHSIT), 2014–2016. Participants Noninstitutionalized Taiwanese nationals aged 65 years and older enrolled in the NAHSIT (N = 923). Measurements Dietary intake was assessed using a 79-item food-frequency questionnaire (FFQ). Presence of 5 frailty phenotypes was determined using modified Fried criteria and are summed into a frailty score. Using data from the NAHSIT (2014–15), reduced rank regression was used to find a dietary pattern that explained maximal degree of variation of the frailty scores. Logistic regression models were used to estimate the association between frailty and dietary pattern. The findings were validated with data from 2016. Results The derived dietary pattern was characterized with a high consumption of fruit, nuts and seeds, tea, vegetables, whole grains, shellfish, milk, and fish. The prevalence of frailty was 7.8% and of prefrailty was 50.8%, defined using the modified Fried criteria. Using data from the NAHSIT (2014–15), the dietary pattern score showed an inverse dose-response relationship with prevalence of frailty and pre-frailty. Individuals in the second dietary pattern tertile were one-third as likely to be frail as those in the first tertile (adjusted odds ratio (aOR) = 0.32, 95% confidence interval (CI) = 0.12−0.85), and those in the third tertile were 4% as likely to be frail as those in the first tertile (aOR = 0.04, 95% CI = 0.01−0.18). The dietary pattern score estimated using FFQ data from the NAHSIT 2016 was also significantly and inversely associated with frailty. Conclusion Individuals with a dietary pattern with more phytonutrient-rich plant foods, tea, omega-3-rich deep-sea fish, and other protein-rich foods such as shellfish and milk had a reduced prevalence of frailty. Further research is necessary to confirm these findings and investigate whether related dietary interventions can reduce frailty in older adults.

Lignocellulosic biomass is a promising feedstock for sustainable production of non-food building-block sugars. This bioconversion process is preferentially carried out through the whole slurry enzymatic saccharification of the pre-treated lignocellulosic substrates. However, dissolved lignin, residual lignin, and lignin-derived phenolic molecules in the pre-treated biomass slurry can all trigger the decrease in activity and stability of cellulases, as well as the unfavorable enzyme recyclability. The hydrolyzing efficiencies can be considerably hindered by the lignin-induced non-productive binding of cellulases through various mechanisms. Three major non-covalent forces, i.e., hydrophobic, electrostatic, and hydrogen bonds interactions, can occur between the amino acid residues in cellulases and the functional groups in lignin. Various strategies such as enzyme engineering, substrate modification, additive blocking have been intensively developed to minimize the cellulase-lignin interactions. To investigate the impacts and benefits of different mechanisms and processes, this paper provides a systematic overview of the current opinions about the non-productive binding of cellulase to lignin. Through better understanding of their interactions it is our hope that the enzyme binding groups in lignin could be properly quenched by using new pre-treatment methods and/or biochemical processing strategies to increase the efficiency of cellulose bioconversion. © 2016 Society of Chemical Industry and John Wiley & Sons, Ltd