Abstract
Background
The triglyceride-glucose index (TyG index) has been regarded as a reliable alternative marker of insulin resistance and an independent predictor of cardiovascular outcomes. ...Whether the TyG index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome (ACS) remains uncertain. The aim of this study was to investigate the prognostic value of the TyG index in patients with diabetes and ACS.
Methods
A total of 2531 consecutive patients with diabetes who underwent coronary angiography for ACS were enrolled in this study. Patients were divided into tertiles according to their TyG index. The primary outcomes included the occurrence of major adverse cardiovascular events (MACEs), defined as all-cause death, non-fatal myocardial infarction and non-fatal stroke. The TyG index was calculated as the ln (fasting triglyceride level mg/dL × fasting glucose level mg/dL/2).
Results
The incidence of MACE increased with TyG index tertiles at a 3-year follow-up. The Kaplan–Meier curves showed significant differences in event-free survival rates among TyG index tertiles (P = 0.005). Multivariate Cox hazards regression analysis revealed that the TyG index was an independent predictor of MACE (95% CI 1.201–1.746; P < 0.001). The optimal TyG index cut-off for predicting MACE was 9.323 (sensitivity 46.0%; specificity 63.6%; area under the curve 0.560; P = 0.001). Furthermore, adding the TyG index to the prognostic model for MACE improved the C-statistic value (P = 0.010), the integrated discrimination improvement value (P = 0.001) and the net reclassification improvement value (P = 0.019).
Conclusions
The TyG index predicts future MACE in patients with diabetes and ACS independently of known cardiovascular risk factors, suggesting that the TyG index may be a useful marker for risk stratification and prognosis in patients with diabetes and ACS.
Nanopore‐based techniques, which mimic the functions of natural ion channels, have attracted increasing attention as unique methods for single‐molecule detection. The technology allows the real‐time, ...selective, high‐throughput analysis of nucleic acids through both biological and solid‐state nanopores. In this Minireview, the background and latest progress in nanopore‐based sequencing and detection of nucleic acids are summarized, and light is shed on a novel platform for nanopore‐based detection.
Adopted from nature: The functions of natural ion channels can be mimicked with both biological and solid‐state nanopores, which have attracted increasing attention for their possible use in the detection and sequencing of DNA. In this Minireview, background and latest progress in this area are summarized and a novel platform for nanopore‐based detection is discussed.
Inspired by the biological processes of molecular recognition and transportation across membranes, nanopore techniques have evolved in recent decades as ultrasensitive analytical tools for individual ...molecules. In particular, nanopore-based single-molecule DNA/RNA sequencing has advanced genomic and transcriptomic research due to the portability, lower costs and long reads of these methods. Nanopore applications, however, extend far beyond nucleic acid sequencing. In this Review, we present an overview of the broad applications of nanopores in molecular sensing and sequencing, chemical catalysis and biophysical characterization. We highlight the prospects of applying nanopores for single-protein analysis and sequencing, single-molecule covalent chemistry, clinical sensing applications for single-molecule liquid biopsy, and the use of synthetic biomimetic nanopores as experimental models for natural systems. We suggest that nanopore technologies will continue to be explored to address a number of scientific challenges as control over pore design improves.
Pyruvate, a pivotal glucose metabolite, is an α-ketoacid that reacts with hydrogen peroxide (H
O
). Its pharmacological precursor, ethyl pyruvate, has shown anti-inflammatory/anti-tissue injury ...effects in various animal models of disease, but failed in a multicenter clinical trial. Since rodents, but not humans, can convert ethyl pyruvate to pyruvate in blood plasma, this additional source of extracellular pyruvate may have contributed to the discrepancy between the species. To examine this possibility, we investigated the kinetics of the reaction under biological conditions and determined the second order rate constant k as 2.360 ± 0.198 M
s
. We then calculated the time required for H
O
elimination by pyruvate. The results show that, with an average intracellular concentration of pyruvate (150 µM), elimination of 95% H
O
at normal to pathological concentrations (0.01-50 µM) requires 141-185 min (2.4-3 hour). With 1,000 µM pyruvate, a concentration that can only exist extracellularly or in cell culture media, 95% elimination of H
O
at 5-200 µM requires 21-25 min. We conclude that intracellular pyruvate, or other α-ketoacids, whose endogenous concentration is controlled by metabolism, have little role in H
O
clearance. An increased extracellular concentration of pyruvate, however, does have remarkable peroxide scavenging effects, considering minimal peroxidase activity in this space.
Pollution by heavy metals limits the area of land available for cultivation of food crops. A potential solution to this problem might lie in the molecular breeding of food crops for phytoremediation ...that accumulate toxic metals in straw while producing safe and nutritious grains. Here, we identify a rice quantitative trait locus we name cadmium (Cd) accumulation in leaf 1 (CAL1), which encodes a defensin-like protein. CAL1 is expressed preferentially in root exodermis and xylem parenchyma cells. We provide evidence that CAL1 acts by chelating Cd in the cytosol and facilitating Cd secretion to extracellular spaces, hence lowering cytosolic Cd concentration while driving long-distance Cd transport via xylem vessels. CAL1 does not appear to affect Cd accumulation in rice grains or the accumulation of other essential metals, thus providing an efficient molecular tool to breed dual-function rice varieties that produce safe grains while remediating paddy soils.
Abstract
Background
Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether ...these findings translate to epidermal growth factor receptor (EGFR)–mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual.
Methods
Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided.
Results
A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial.
Conclusions
As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.
Perovskite Light‐emitting diodes (PeLEDs) have emerged as a promising technique for future high‐definition displays due to their outstanding electroluminescent characters. However, the development of ...blue PeLEDs toward practical applications is seriously hindered by their inferior performance, which mainly arises from the detrimental halide ionic behavior and thus severe nonradiative recombination in mixed‐halide blue perovskite materials. Herein, efficient sky‐blue PeLEDs featuring spectrally stable emission at 483 nm are realized by employing bifunctional passivators of Lewis‐base benzoic acid anions and alkali metal cations to simultaneously passivate the under‐coordinated lead atoms and suppress halide ion migration. A decent external quantum efficiency (EQE) of 16.58% and a maximum EQE of 18.65% are achieved, which is further boosted to 28.82% through the optical outcoupling enhancement. This work demonstrates unique insight into the generality and individuality of this category of benzoates and puts forward a feasible guidance in choosing appropriate additives for efficient perovskite materials.
Defect passivation and the suppression of halide ion migration are simultaneously achieved in mixed‐halide perovskite materials via the incorporation of bifunctional additives containing Lewis‐base group and alkali metal ions. Efficient sky‐blue perovskite light‐emitting diodes achieve an external quantum efficiency of 16.58%, which is further boosted to 28.82% by the optical outcoupling enhancement.
The mechanisms underlying the two‐way relationship between diabetes mellitus (DM) and periodontitis are unclear. We examined a possible effect of galectin‐3 (Gal‐3), a factor in DM and bone ...metabolism, on periodontitis with or without DM. Using enzyme‐linked immunosorbent assay, we detected saliva Gal‐3 in patients with periodontitis, with or without type 2 diabetes mellitus (T2DM). In animal models, we measured periodontal bone microarchitecture via micro computed tomography, and detected Gal‐3, Runt‐related transcription factor 2 (Runx2), and interleukin‐6 (IL‐6) expression in alveolar bone. Applying dual luciferase reporter assay, we explored the target binding of miR‐124‐3p and Gal‐3. We examined osteocyte‐derived exosomes with transmission electron microscopy and detected miR‐124‐3p, Gal‐3, and IL‐6 expression in exosomes. Saliva Gal‐3 was increased in DM compared with controls but decreased in patients with moderate periodontitis and DM compared with those who had moderate periodontitis only. Alveolar bone mass was increased in DM and exacerbated in DM with periodontitis. Gal‐3 and Runx2 were both increased in periodontitis and DM compared with controls, but decreased in DM with periodontitis compared with DM alone. MiR‐124‐3p targeted and inhibited Gal‐3 expression in vitro. Osteocytes secreted exosomes carrying miR‐124‐3p, Gal‐3, and IL‐6, which were influenced by high glucose. These findings indicate that osteocyte‐derived exosomes carrying miR‐124‐3p may regulate Gal‐3 expression of osteoblasts, especially under high‐glucose conditions, suggesting a possible mechanism for DM‐related alveolar bone pathologies.
Single‐entity electrochemistry is a powerful tool that enables the study of electrochemical processes at interfaces and provides insights into the intrinsic chemical and structural heterogeneities of ...individual entities. Signal processing is a critical aspect of single‐entity electrochemical measurements and can be used for data recognition, classification, and interpretation. In this review, we summarize the recent five‐year advances in signal processing techniques for single‐entity electrochemistry and highlight their importance in obtaining high‐quality data and extracting effective features from electrochemical signals, which are generally applicable in single‐entity electrochemistry. Moreover, we shed light on electrochemical noise analysis to obtain single‐molecule frequency fingerprint spectra that can provide rich information about the ion networks at the interface. By incorporating advanced data analysis tools and artificial intelligence algorithms, single‐entity electrochemical measurements would revolutionize the field of single‐entity analysis, leading to new fundamental discoveries.
This Minireview summarizes the latest advances in data processing techniques for single‐entity electrochemistry towards achieving automation, real‐time monitoring, increased sensitivity, as well as improved temporal and current resolution.
•An optimal sizing method is developed for a hybrid PV/diesel/ESS ship power system.•The output of PV along a navigation route is explored for the ship power system.•Five operating conditions of the ...load in the ship power system are modeled.•The impact of various prices of PV on cost is studied.
Owing to the strict restrictions imposed by the Marine Pollution Protocol and the rapid development of renewable energy, the use of solar generation and energy storage systems in ship power systems has been increasingly attracting attention. However, the improper sizing of a hybrid power generation system in a ship power system will result in a high investment cost and increased greenhouse gas emission. This paper proposes a method for determining the optimal size of the photovoltaic (PV) generation system, the diesel generator and the energy storage system in a stand-alone ship power system that minimizes the investment cost, fuel cost and the CO2 emissions. The power generation from PV modules on a ship relies on the date, local time, time zone, longitude and latitude along a navigation route and is different from the conditions of power systems on land. Thus, a method, which takes the seasonal and geographical variation of solar irradiations and temperatures along the route from Dalian in China to Aden in Yemen into account, for correcting the output of PV modules is developed in this paper. The proposed method considers five conditions along the navigation route to model the total ship load. Four cases are studied in details to demonstrate the applicability of the proposed algorithm.
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