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Aggregation-induced emission luminogens disclose cellular cycle-dependent telomerase action within cancer malignancy tissue.
Introduction Antiarrhythmic drugs therapies are currently going through a turning point. The high risk that exists during the treatments has led to an ongoing search for new non-invasive toxicity risk biomarkers. Methods We propose the use of spatial biomarkers obtained through the quaternion algebra, evaluating the dynamics of the cardiac electrical vector in a non-invasive way in order to detect abnormal changes in ventricular heterogeneity. In groups of patients with and without history of Torsade de Pointes undergoing a Sotalol challenge, we compute the radius and the linear and angular velocities of QRS complex and T-wave loops. From these signals we extract significant features in order to compute a risk patient classifier. Results Using machine learning techniques and statistical analysis, the combinations of few indices reach a pair of sensitivity/specificity of 100%/100% when separating patients with arrhythmogenic substrate. Several biomarkers not only measure drug-induced changes significantly but also observe differences in at-risk patients outperforming current standards. Discussion Alternative biomarkers were able to describe pre-existing risk of patients. Given the high levels of significance and performance, these results could contribute to a better understanding of the torsadogenic substrate and to the safe development of drug therapies.This study reports on a comparative study of acid hydrotropic fractionation (AHF) of birch wood using maleic acid (MA) and p-toluenesulfonic acid (p-TsOH). Under the same level of delignification, lignin dissolved by MA is much less condensed with a higher content of ether aryl β-O-4 linkages. Lignin depolymerization dominated in MA hydrotropic fractionation (MAHF) and resulted in a single lower Mw peak, in contrast to the competitive depolymerization and repolymerization in p-TsOH HF with a bimodal distribution. The less condensed MA-dissolved lignin facilitated catalytic conversion to monophenols. Carboxylation of residual lignin in fractionated cellulosic solids (WIS) enhanced enzymatic saccharification by decreasing nonproductive cellulase binding to lignin. At a low cellulase loading of 10 FPU g-1 glucan, saccharification of WIS-MT120 from MAHF at 120 °C was 95% compared with 48% for WIS-PT85 from p-TsOH HF at 85 °C under the same level of delignification of 63%. Residual lignin carboxylation also facilitated nanofibrillation of WIS for producing lignin-containing cellulose nanofibrils (LCNFs) through an enhanced lignin lubrication effect to substantially decrease fibrillation energy. LCNFs from only one pass of microfluidization of WIS-MT120 have the same morphology as those from WIS-PT85 after three passes. MA also has a lower solubility and higher minimal hydrotropic concentration, which facilitated acid recovery. MA is FDA-approved as an indirect food additive (21CFR175-177), affording significant advantages compared with p-TsOH for biorefinery applications.No funding was required for this project. The authors are or have been members of the Format Executive Committee.No funding supported the writing of this commentary. The author has nothing to disclose.Objective This study aimed to clarify whether plasma acrolein level actually increases in rheumatoid arthritis (RA) patients, and to elucidate whether any relationship exists between the levels and the RA background variables.Methods Plasma levels of protein-conjugated acrolein (PC-Acro) in 84 patients (RA group) and 298 normal individuals (Control group) were measured by enzyme-linked immunosorbent assay procedures. The data were statistically analyzed with Wilcoxon rank-sum test, multiple logistic regression analyses and Spearman's rank correlation coefficient.Results The RA group showed significantly higher PC-Acro levels than the Control group (median [interquartile range] 80.5 [63.2-105.2] and 65.9 [58.9-78.1] nmol/ml, respectively). Of background factors giving influence to PC-Acro level in the combination of the two groups, "diagnosis of RA positive" indicated strong correlation to high PC-Acro level (odds ratio 2.96; 95% confidence interval 1.54-5.71). These increases of PC-Acro in the RA patients did not correlate to their disease duration and/or inflammatory variables PC-Acro level could elevate even in early RA patients showing negative inflammatory findings.Conclusion Plasma levels of PC-Acro increased with RA, but the levels did not correlate with RA background variables. This report provides the basis for further studies of early diagnosis of RA as well as its pathogenesis.Trypanosoma cruzi, the etiological agent of Chagas disease, is responsible for the infection of millions of people worldwide and it is a public health problem, without an effective cure. Four fragments with antimicrobial potential from the hemocyanin of Penaeus monodon shrimp were identified using a computer software AMPA. The present study aimed to evaluate the antichagasic effect of these four peptides (Hmc364-382, Hmc666-678, Hmc185-197 and Hmc476-498). The peptides were tested against the epimastigote, trypomastigote and amastigote forms of Trypanosoma cruzi Y strain (benznidazole-resistant strain) and cytotoxicity in mammalian cells was evaluated against LLC-MK2 lineage cells. Two fragments (Hmc364-382, Hmc666-678) showed activity against the epimastigote and trypomastigote forms and their selectivity index (SI) was calculated. The Hmc364-382 peptide was considered the most promising (SI > 50) one and it was used for further studies, using flow cytometry analyses with specific molecular probes and scanning electron microscopy (SEM). Hmc364-382 was able to induce cell death in T. cruzi through necrosis, observed by loss of membrane integrity in flow cytometry analyses and pore formation in SEM. Overall, Hmc364-382 open perspectives to the development of new antichagasic agents.Species within the green algal order, Cladophorales, have an unconventional plastome structure where individual coding regions or small numbers of genes occur as linear single-stranded DNAs folded into hairpin structures. Another group of photosynthetic organisms with an equivalently reduced chloroplast genome are the peridinin dinoflagellates of the Alveolata eukaryotic lineage whose plastomes are mini-circles carrying one or a few genes required for photosynthesis. One unusual aspect of the Alveolata is the polyuridylylation of mRNA 3' ends among non-peridinin dinoflagellates, and the chromerid algae. This study was conducted to understand if an unconventional highly-reduced plastome structure co-occurs with unconventional RNA processing. To address this, the 5' and 3' mRNA termini of the known chloroplast genes of Pithophora roettleri (order Cladophorales), were analyzed for evidence of post-transcriptional processing. check details Circular Reverse Transcriptase PCR (cRT-PCR) followed by deep sequencing of the amplicons was used to analyze 5' and 3' mRNA termini. Evidence of several processing events were collected, most notably the 3' termini of six of the eight genes were polyuridylylated, which has not been reported for any lineage outside of the Alveolata. Other processing events include poly(A) and heteropolymeric 3' additions, 5' primary transcript start sites, as well as the presence of circularized RNAs. Five other species representing other green algal lineages, were also tested and poly(U) additions appear to be limited to the order Cladophorales. These results demonstrate that chloroplast mRNA polyuridylylation is not the sole provenance of photosynthetic alveolates and may have convergently evolved in two distinct photosynthetic lineages.Insufficient retention of water in adsorbed salivary conditioning films (SCFs) due to altered saliva secretion can lead to oral dryness (xerostomia). Patients with xerostomia sometimes are given artificial saliva, which often lacks efficacy due to the presence of exogenous molecules with limited lubrication properties. Recombinant supercharged polypeptides (SUPs) improve salivary lubrication by enhancing functionality of endogenously available salivary proteins, which is in stark contrast to administration of exogenous lubrication enhancers. This novel approach is based on establishing a layered architecture enabled by electrostatic bond formation to stabilize and produce robust SCFs in vitro. Here, we first determined the optimal molecular weight of SUPs to achieve the best lubrication performance employing biophysical and in vitro friction measurements. Next, in an ex vivo tongue-enamel friction system, stimulated whole saliva from patients with Sjögren syndrome was tested to transfer this strategy to a pre-clinical situation. Out of a library of genetically engineered cationic polypeptides, the variant SUP K108cys that contains 108 positive charges and two cysteine residues at each terminus was identified as the best SUP to restore oral lubrication. Employing this SUP, the duration of lubrication (Relief period) for SCFs from healthy and patient saliva was significantly extended. For patient saliva, lubrication duration was increased from 3.8 min to 21 min with SUP K108cys treatment. Investigation of the tribochemical mechanism revealed that lubrication enhancement is due to electrostatic stabilization of SCFs and mucin recruitment, which is accompanied by strong water fixation and reduced water evaporation.Foliar functional traits are widely used to characterize leaf and canopy properties that drive ecosystem processes and to infer physiological processes in Earth system models. Imaging spectroscopy provides great potential to map foliar traits to characterize continuous functional variation and diversity, but few studies have demonstrated consistent methods for mapping multiple traits across biomes. With airborne imaging spectroscopy data and field data from 19 sites, we developed trait models using partial least squares regression, and mapped 26 foliar traits in 7 NEON (National Ecological Observatory Network) ecoregions (domains) including temperate and subtropical forests and grasslands of eastern North America. Model validation accuracy varied among traits (normalized RMSE, 9.1-19.4%; R2 , 0.28-0.82), with phenolic concentration, leaf mass per area and equivalent water thickness performing best across domains. Across all trait maps, 90% of vegetated pixels had reasonable values for one trait, and 28-81% provided high confidence for multiple traits concurrently. Maps of 26 traits and their uncertainties for eastern U.S. NEON sites are available for download, and are being expanded to the western U.S. and tundra/boreal zone. These data enable better understanding of trait variations and relationships over large areas, calibration of ecosystem models, and assessment of continental-scale functional diversity.Objective This study aimed to clarify whether plasma acrolein level actually increases in rheumatoid arthritis (RA) patients, and to elucidate whether any relationship exists between the levels and the RA background variables.Methods Plasma levels of protein-conjugated acrolein (PC-Acro) in 84 patients (RA group) and 298 normal individuals (Control group) were measured by enzyme-linked immunosorbent assay procedures. The data were statistically analyzed with Wilcoxon rank-sum test, multiple logistic regression analyses and Spearman's rank correlation coefficient.Results The RA group showed significantly higher PC-Acro levels than the Control group (median [interquartile range] 80.5 [63.2-105.2] and 65.9 [58.9-78.1] nmol/ml, respectively). Of background factors giving influence to PC-Acro level in the combination of the two groups, "diagnosis of RA positive" indicated strong correlation to high PC-Acro level (odds ratio 2.96; 95% confidence interval 1.54-5.71). These increases of PC-Acro in the RA patients did not correlate to their disease duration and/or inflammatory variables PC-Acro level could elevate even in early RA patients showing negative inflammatory findings.
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