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BackgroundGlucose variability is one of components of the dysglycemia in diabetes and may play an important role in development of diabetic vascular complications. The objective of this study was to assess the relationship between glycemic variability determined by a continuous glucose monitoring (CGM) system and the presence and severity of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM).MethodsIn 344 T2DM patients with chest pain, coronary angiography revealed CAD (coronary stenosis ≥ 50% luminal diameter narrowing) in 252 patients and 92 patients without CAD. Gensini score was used to assess the severity of CAD. All participants' CGM parameters and biochemical characteristics were measured at baseline.ResultsDiabetic patients with CAD were older, and more were male and cigarette smokers compared with the controls. Levels of the mean amplitude of glycemic excursions (MAGE) (3.7 ± 1.4 mmol/L vs. 3.2 ± 1.2 mmol/L, p < 0.001), postprandial glucose excursion (PPGE) (3.9 ± 1.6 mmol/L vs. 3.6 ± 1.4 mmol/L, p = 0.036), serum high-sensitive C-reactive protein (hs-CRP) (10.7 ± 12.4 mg/L vs. 5.8 ± 6.7 mg/L, p < 0.001) and creatinine (Cr) (87 ± 23 mmol/L vs. 77 ± 14 mmol/L, p < 0.001) were significantly higher in patients with CAD than in patients without CAD. Gensini score closely correlated with age, MAGE, PPGE, hemoglobin A1c (HbA1c), hs-CRP and total cholesterol (TC). Multivariate analysis indicated that age (p < 0.001), MAGE (p < 0.001), serum levels of HbA1c (p = 0.022) and hs-CRP (p = 0.005) were independent determinants for Gensini score. Logistic regression analysis revealed that MAGE ≥ 3.4 mmol/L was an independent predictor for CAD. The area under the receiver-operating characteristic curve for MAGE (0.618, p = 0.001) was superior to that for HbA1c (0.554, p = 0.129).ConclusionsThe intraday glycemic variability is associated with the presence and severity of CAD in patients with T2DM. Effects of glycemic excursions on vascular complications should not be neglected in diabetes.

SUMMARYPlant roots respond to environmental stresses or the exogenous plant hormone abscisic acid (ABA) by undergoing marked physiological and morphological changes. We show here that PERK4, a gene that encodes a member of the Arabidopsis thaliana proline-rich extensin-like receptor kinase family, plays an important role in ABA responses. Mutation of PERK4 by T-DNA insertion decreased sensitivity to ABA with respect to seed germination, seedling growth and primary root tip growth. The effect on root growth was due to enhanced cell elongation rather than cell division. The cytosolic free calcium concentration and Ca 2+ channel currents were lower in perk4 root cells than in wild-type cells in the presence of ABA. Root growth was similar in wild-type and perk4 plants after the application of a Ca 2+ channel blocker. PERK4 localised to the plasma membrane, and was shown to be an ABA-and Ca 2+ -activated protein kinase. Our data suggest that the receptor-like kinase encoded by PERK4 functions at an early stage of ABA signalling to inhibit root cell elongation by perturbing Ca 2+ homeostasis.

Most land plants have evolved a mutualistic symbiosis with arbuscular mycorrhiza (AM) fungi that improve nutrient acquisition from the soil. In return, up to 20% of host plant photosynthate is transferred to the mycorrhizal fungus in the form of lipids and sugar. Nutrient exchange must be regulated by both partners in order to maintain a reliable symbiotic relationship. However, the mechanisms underlying the regulation of lipid transfer from the plant to the AM fungus remain elusive. Here, we show that the Medicago truncatula AP2/EREBP transcription factor WRI5a, and likely its two homologs WRI5b/Erf1 and WRI5c, are master regulators of AM symbiosis controlling lipid transfer and periarbuscular membrane formation. We found that WRI5a binds AW-box cis-regulatory elements in the promoters of M. truncatula STR, which encodes a periarbuscular membrane-localized ABC transporter required for lipid transfer from the plant to the AM fungus, and MtPT4, which encodes a phosphate transporter required for phosphate transfer from the AM fungus to the plant. The hairy roots of the M. truncatula wri5a mutant and RNAi composite plants displayed impaired arbuscule formation, whereas overexpression of WRI5a resulted in enhanced expression of STR and MtPT4, suggesting that WRI5a regulates bidirectional symbiotic nutrient exchange. Moreover, we found that WRI5a and RAM1 (Required for Arbuscular Mycorrhization symbiosis 1), which encodes a GRASdomain transcription factor, regulate each other at the transcriptional level, forming a positive feedback loop for regulating AM symbiosis. Collectively, our data suggest a role for WRI5a in controlling bidirectional nutrient exchange and periarbuscular membrane formation via the regulation of genes involved in the biosynthesis of fatty acids and phosphate uptake in arbuscule-containing cells.

OBJECTIVEDysglycemia is associated with poorer prognosis in patients with acute myocardial infarction (AMI). Whether admission glycemic variability (GV) has important value in prognosis of AMI patients is still unknown. The aim of the study is to investigate the prognostic value of admission GV, glucose, and glycosylated hemoglobin (HbA1c) in AMI patients.RESEARCH DESIGN AND METHODSWe measured blood glucose, HbA1c, and GV on admission in 222 consecutive patients with diagnosed AMI. GV, indicated as the mean amplitude of glycemic excursions (MAGE), was determined by a continuous glucose monitoring system. MAGE was categorized as ≥3.9 or <3.9 mmol/L, admission glucose as ≥8.61 or <8.61 mmol/L, and HbA1c as ≥6.5 or <6.5%. Participants were followed up prospectively for 12 months. The relationship of admission MAGE, glucose, and HbA1c to the major adverse cardiac event (MACE) of AMI patients was analyzed.RESULTSIn 222 enrolled patients with AMI, the rate of MACE by MAGE category (<3.9 or ≥3.9 mmol/L) was 8.4 and 24.1%, respectively (P = 0.001), by admission glucose category (<8.61 or ≥8.61 mmol/L) was 10.1 and 21.6%, respectively (P = 0.020), and by HbA1c category (<6.5 vs. ≥6.5%) was 10.7 versus 18.7%, respectively (P = 0.091). In multivariate analysis, high MAGE level was significantly associated with incidence of MACE (hazard ratio 2.419 [95% CI 1.273–9.100]; P = 0.017) even after adjusting for Global Registry of Acute Coronary Events risk score, but admission glucose and HbA1c was not.CONCLUSIONSElevated admission GV appears more important than admission glucose and prior long-term abnormal glycometabolic status in predicting 1-year MACE in patients with AMI.

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Prime editing is a novel and universal CRISPR/Cas-derived precision genome-editing technology that has been recently developed. However, low efficiency of prime editing has been shown in transgenic rice lines. We hypothesize that enhancing pegRNA expression could improve prime-editing efficiency. In this report, we describe two strategies for enhancing pegRNA expression. We construct a prime editing vector harboring two pegRNA variants for W542L and S621I double mutations in ZmALS1 and ZmALS2. Compared with previous reports in rice, we achieve much higher prime-editing efficiency in maize. Our results are inspiring and provide a direction for the optimization of plant prime editors.

Ammonium (NH 4+ ) is both a necessary nutrient and an important signal in plants, but can be toxic in excess. Ammonium sensing and regulatory mechanisms in plant cells have not been fully elucidated. To decipher the complex network of NH 4 + signaling, we analyzed [Ca 2+ ] cyt -associated protein kinase (CAP) genes, which encode signaling components that undergo marked changes in transcription levels in response to various stressors. We demonstrated that CAP1, a tonoplast-localized receptor-like kinase, regulates root hair tip growth by maintaining cytoplasmic Ca 2+ gradients. A CAP1 knockout mutant (cap1-1) produced elevated levels of cytoplasmic NH 4 + . Furthermore, root hair growth of cap1-1 was inhibited on Murashige and Skoog medium, but NH 4 + depletion reestablished the Ca 2+ gradient necessary for normal growth. The lower net NH 4 + influx across the vacuolar membrane and relatively alkaline cytosolic pH of cap1-1 root hairs implied that mutation of CAP1 increased NH 4 + accumulation in the cytoplasm. Furthermore, CAP1 functionally complemented the npr1 (nitrogen permease reactivator protein) kinase yeast mutant, which is defective in high-affinity NH 4 + uptake via MEP2 (methylammonium permease 2), distinguishing CAP1 as a cytosolic modulator of NH 4 + levels that participates in NH 4 + homeostasis-regulated root hair growth by modulating tip-focused cytoplasmic Ca 2+ gradients.