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85 ± 2.57 years (AFL without ablation group) and 8.31 ± 4.53 years (AFL ablation group). Atrial flutter with ablation patients had lower risks of all-cause mortality (HR 0.68, P < 0.001), CV deaths (HR 0.78, P = 0.001), HF hospitalization (HR 0.84, P = 0.01), and stroke (HR 0.80, P = 0.01).

Catheter ablation for AFL in patients without prior AF was associated with lower risks of all-cause mortality and CV events compared with AFL patients without ablation during long-term follow-ups.

Catheter ablation for AFL in patients without prior AF was associated with lower risks of all-cause mortality and CV events compared with AFL patients without ablation during long-term follow-ups.Cytosolic peptide N-glycanase (PNGase; NGLY1), an enzyme responsible for de-glycosylation of N-glycans on glycoproteins, is known to play pivotal roles in a variety of biological processes. In 2012, NGLY1 deficiency, a rare genetic disorder, was reported and since then, more than 100 patients have now been identified worldwide. Patients with this disease exhibit several common symptoms that are caused by the dysfunction of NGLY1. However, correlation between the severity of patient symptoms and the extent of the reduction in NGLY1 activity in these patients remains to be clarified, mainly due to the absence of a facile quantitative assay system for this enzyme, especially in a crude extract as an enzyme source. In this study, a quantitative, non-radioisotope (RI)-based assay method for measuring recombinant NGLY1 activity was established using a BODIPY-labeled asialoglycopeptide (BODIPY-ASGP) derived from hen eggs. With this assay, the activities of 27 recombinant NGLY1 mutants that are associated with the deficiency were examined. It was found that the activities of 3 (R469X, R458fs, and H494fs) out of the 27 recombinant mutant proteins were 30-70 percent of the activities of wild-type NGLY1. We further developed a method for measuring endogenous NGLY1 activity in crude extracts derived from cultured cells, patients' fibroblasts, iPS cells or peripheral blood mononuclear cells (PBMCs), using a glycosylated cyclopeptide (GCP) that exhibited resistance to the endogenous proteases in the extract. Our methods will not only provide new insights into the molecular mechanism responsible for this disease but also promises to be applicable for its diagnosis.The urocortins (Ucns) belong to the corticotropin-releasing factor (CRF) family of peptides and have multiple effects within the central nervous and the cardiovascular systems. With growing evidence indicating significant cardioprotective properties and cardiovascular actions of these peptides, the question arises as to whether the plasma profiles of the Ucns are altered in pathologic settings. While reports have shown conflicting results and findings have not been corroborated in multiple independent cohorts, it seems likely that plasma Ucn concentrations are elevated in multiple cardiovascular conditions. The degree of increase and accurate determination of circulating values of the Ucns requires further validation.The light attenuation process within a plant canopy defines energy capture and vertical distribution of light and nitrogen (N). The vertical light distribution can be quantitatively described with the extinction coefficient (k), which associates the fraction of intercepted photosynthetically active radiation (fPARi) with the leaf area index (LAI). Lower values of k correspond to upright leaves and homogeneous vertical light distribution, increasing radiation use efficiency (RUE). Yield gains in maize (Zea mays L.) were accompanied by increases in optimum plant density and leaf erectness. Thus, the yield-driven breeding programs and management changes, such as reduced row spacing, selected a more erect leaf habit under different maize production systems (e.g., China and the USA). In this study, data from Argentina revealed that k decreased at a rate of 1.1% year-1 since 1989, regardless of plant density and in agreement with Chinese reports (1.0% year-1 since 1981). A reliable assessment of changes in k over time is critical for predicting (i) modifications in resource use efficiency (e.g. CHIR-99021 research buy radiation, water, and N), improving estimations derived from crop simulation models; (ii) differences in productivity caused by management practices; and (iii) limitations to further exploit this trait with breeding.Synthetic sugar analogs are widely applied in metabolic oligosaccharide engineering (MOE) and as novel drugs to interfere with glycoconjugate biosynthesis. However, mechanistic insights on their exact cellular metabolism over time are mostly lacking. We combined ion-pair UHPLC-QqQ mass spectrometry using tributyl- and triethylamine buffers for sensitive analysis of sugar metabolites in cells and organisms and identified low abundant nucleotide sugars, such as UDP-arabinose in human cell lines and CMP-sialic acid (CMP-NeuNAc) in Drosophila. Furthermore, MOE revealed that propargyloxycarbonyl (Poc) labeled ManNPoc was metabolized to both CMP-NeuNPoc and UDP-GlcNPoc. link2 Finally, time-course analysis of the effect of antitumor compound 3Fax-NeuNAc by incubation of B16-F10 melanoma cells with N-acetyl-D-[UL-13C6]glucosamine revealed full depletion of endogenous ManNAc 6-phosphate and CMP-NeuNAc within 24 hour. Thus, dynamic tracing of sugar metabolic pathways provides a general approach to reveal time-dependent insights into the metabolism of synthetic sugars, which is important for the rational design of analogs with optimized effects.We recently discovered that human neutrophils express immunomodulatory glycoproteins carrying unusual and highly truncated paucimannosidic N-glycans (Man1-3GlcNAc2Fuc0-1), but their biosynthesis remains elusive. Guided by the well-characterized truncation pathway in invertebrates and plants in which the N-acetyl-β-D-hexosaminidase (Hex) isoenzymes catalyze paucimannosidic protein (PMP) formation, we here set out to test if the homologous human Hex α and β subunits encoded by HEXA and HEXB drive a similar truncation pathway in human neutrophils. To this end, we performed quantitative glycomics and glycoproteomics of several CRISPR-Cas9-edited Hex-disrupted neutrophil-like HL-60 mutants (HEXA-KO and HEXB-KO) and matching unedited cell lines. Hex disruption was validated using next-generation sequencing, enzyme-linked immunosorbent assay (ELISA), quantitative proteomics and Hex activity assays. link3 Excitingly, all Hex-disrupted mutants displayed significantly reduced levels of paucimannosylation, particularly Man2-3GlcNAc2Fuc1, relative to unedited HL-60 suggesting that both HEXA and HEXB contribute to PMP formation via a hitherto unexplored truncation pathway in neutrophils. Quantitative N-glycomics indeed demonstrated reduced utilization of a putative noncanonical truncation pathway in favor of the canonical elongation pathway in all Hex-disrupted mutants relative to unedited controls. Quantitative glycoproteomics recapitulated the truncation-to-elongation switch in all Hex-disrupted mutants and showed a greater switch for N-glycoproteins cotrafficking with Hex to the azurophilic granules of neutrophils such as myeloperoxidase. Finally, we supported the Hex-PMP relationship by documenting that primary neutrophils isolated from an early-onset Sandhoff disease patient (HEXB-/-) displayed dramatically reduced paucimannosylation relative to neutrophils from an age-matched unaffected donor. We conclude that both human Hex α and β mediate PMP formation via a putative noncanonical truncation pathway in neutrophils.

Prior research is limited and inconsistent on the degree to which elder mistreatment (EM) is associated with mortality. This study uses data from a 10-year, prospective, population-based study of EM to determine the adjusted effects of EM on older adult mortality, after controlling for other health and socioeconomic covariates.

The New York State Elder Mistreatment Prevalence Study conducted a random-sample telephone survey of older adults (n = 4 156) in 2009 (Wave 1). The current study employs EM and covariate data from Wave 1 and data on mortality status through Wave 2 (2019). EM was operationalized both as experiencing EM and as severity of EM. The survey measured overall EM and separate subtypes (emotional, physical, and financial abuse, and neglect).

The hypothesis was not supported that abused and neglected older people would have higher rates of death over the study. Individuals who were victims of EM were no more likely to die over the following 10 years, compared with those who were not mistreated, after controlling for covariates. Furthermore, the severity of EM, as measured by the frequency of mistreatment behaviors, also was not associated with mortality risk.

The finding that self-reported EM did not raise the risk of earlier death in this sample is encouraging. Future research should work to identify factors that may moderate the relationship between EM and mortality, such as social support/isolation, quality of family relationships, or involvement with formal support service systems.

The finding that self-reported EM did not raise the risk of earlier death in this sample is encouraging. Future research should work to identify factors that may moderate the relationship between EM and mortality, such as social support/isolation, quality of family relationships, or involvement with formal support service systems.O-GlcNAcylation is a post-translational modification that links metabolism with signal transduction. High O-GlcNAcylation appears to be the general characteristic of cancer cells. It promotes the invasion, metastasis, proliferation and survival of tumor cells, and alters many metabolic pathways. Glycogen metabolism increases in a wide variety of tumors, suggesting that it is an important aspect of cancer pathophysiology. Herein we focused on the O-GlcNAcylation of liver glycogen phosphorylase (PYGL), an important catabolism enzyme in the glycogen metabolism pathway. PYGL expressed in both HEK 293 T and HCT116 were modified by O-GlcNAc. And both PYGL O-GlcNAcylation and phosphorylation of Ser15 (pSer15) were decreased under glucose and insulin, while increased under glucagon and Na2S2O4 (hypoxia) conditions. Then, we identified the major O-GlcNAcylation site to be Ser430, and demonstrated that pSer15 and Ser430 O-GlcNAcylation were mutually reinforced. Lastly, we found that Ser430 O-GlcNAcylation was fundamental for PYGL activity. Thus, O-GlcNAcylation of PYGL positively regulated pSer15 and therefore its enzymatic activity. Our results provided another molecular insight into the intricate post-translational regulation network of PYGL.Cluster randomized trials (CRTs) randomly assign an intervention to groups of individuals (e.g., clinics or communities) and measure outcomes on individuals in those groups. While offering many advantages, this experimental design introduces challenges that are only partially addressed by existing analytic approaches. First, outcomes are often missing for some individuals within clusters. Failing to appropriately adjust for differential outcome measurement can result in biased estimates and inference. Second, CRTs often randomize limited numbers of clusters, resulting in chance imbalances on baseline outcome predictors between arms. Failing to adaptively adjust for these imbalances and other predictive covariates can result in efficiency losses. To address these methodological gaps, we propose and evaluate a novel two-stage targeted minimum loss-based estimator to adjust for baseline covariates in a manner that optimizes precision, after controlling for baseline and postbaseline causes of missing outcomes. Finite sample simulations illustrate that our approach can nearly eliminate bias due to differential outcome measurement, while existing CRT estimators yield misleading results and inferences.