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Abstract Aims We intended to characterize the superiority of triglyceride glucose‐body mass index (TyG‐BMI) in predicting type 2 diabetes mellitus (T2DM) compared with triglyceride glucose (TyG) and homeostatic model assessment for insulin resistance (HOMA‐IR). Methods A total of 699 nondiabetic participants in the Da Qing IGT and Diabetes Study were involved in the present analysis and classified according to the median of baseline TyG‐BMI, namely the G1 (low TyG‐BMI) and G2 (high TyG‐BMI) groups. Information on developing diabetes was assessed from 1986 to 2020. Results During the 34‐year follow‐up, after adjustment for confounders, the G2 group had a higher risk of developing type 2 diabetes than the G1 group (hazard ratio [HR]: 1.92, 95% confidence interval [CI]: 1.51–2.45, p 0.05). Time‐dependent receiver operator characteristics curves suggested that TyG‐BMI exhibited higher predictive ability than TyG (6‐year: area under the curve [AUC]TyG‐BMI vs. AUCTyG, 0.78 vs. 0.70, p = 0.03; 34‐year: AUCTyG‐BMI vs. AUCTyG, 0.79 vs. 0.73, p = 0.04) and HOMA‐IR (6‐year: AUCTyG‐BMI vs. AUCHOMA‐IR, 0.78 vs. 0.70, p = 0.07; 34‐year: AUCTyG‐BMI vs. AUCHOMA‐IR, 0.79 vs. 0.71, p = 0.04) in both short and long terms, and the thresholds of TyG‐BMI to predict type 2 diabetes were relatively stable (195.24–208.41) over the 34‐year follow‐up. Conclusions In this post hoc study, higher TyG‐BMI was associated with an increased risk of type 2 diabetes and demonstrated better predictability than TyG and HOMA‐IR, favoring the application of TyG‐BMI as a potential tool for evaluating the risk of type 2 diabetes in clinical practice.

Abstract The structural diversity of biological macromolecules in different environments contributes complexity to enzymological processes vital for cellular functions. Fluorescence resonance energy transfer and electron microscopy are used to investigate the enzymatic reaction of T4 DNA ligase catalyzing the ligation of nicked DNA. The data show that both the ligase–AMP complex and the ligase–AMP–DNA complex can have four conformations. This finding suggests the parallel occurrence of four ligation reaction pathways, each characterized by specific conformations of the ligase–AMP complex that persist in the ligase–AMP–DNA complex. Notably, these complexes have DNA bending angles of ≈0°, 20°, 60°, or 100°. The mechanism of parallel reactions challenges the conventional notion of simple sequential reaction steps occurring among multiple conformations. The results provide insights into the dynamic conformational changes and the versatile attributes of T4 DNA ligase and suggest that the parallel multiple reaction pathways may correspond to diverse T4 DNA ligase functions. This mechanism may potentially have evolved as an adaptive strategy across evolutionary history to navigate complex environments.

Abstract Left ventricular hypertrophy and fibrosis are major risk factors for heart failure, which require timely and effective treatment. Genetic therapy has been shown to ameliorate hypertrophic cardiac damage. In this study, it is found that in mice, the dopamine D5 receptor (D5R) expression in the left ventricle (LV) progressively decreases with worsening of transverse aortic constriction‐induced left ventricular hypertrophy. Then, a reversible treatment of left ventricular hypertrophy with Drd5 nucleic acids delivered by tobramycin‐based hyperbranched polyaminoglycoside (SS‐HPT) is studied. The heart‐specific increase in D5R expression by SS‐HPT/Drd5 plasmid in the early stage of left ventricular hypertrophy attenuates cardiac hypertrophy and fibrosis by preventing oxidative and endoplasmic reticulum (ER) stress and ameliorating autophagic dysregulation. By contrast, SS‐HPT/Drd5 siRNA promotes the progression of left ventricular hypertrophy and accelerates the deterioration of myocardial function into heart failure. The reduction in cardiac D5R expression and dysregulated autophagy are observed in patients with hypertrophic cardiomyopathy and heart failure. The data show a cardiac‐specific beneficial effect of SS‐HPT/Drd5 plasmid on myocardial remodeling and dysfunction, which may provide an effective therapy of patients with left ventricular hypertrophy and heart failure.

Background Pro‐NTs (precursor of neurotrophins) and their receptor p75 are potential targets for preventing microvascular dysfunction induced by myocardial ischemia–reperfusion injury (IRI). p75ECD (ectodomain of neurotrophin receptor p75) may physiologically produce neurocytoprotective effects by scavenging pro‐NTs. We therefore hypothesized that p75ECD may have a cardioprotective effect on IRI through microvascular mechanisms. Methods and Results Myocardial IRI was induced in Sprague‐Dawley rats by occluding the left main coronary arteries for 45 minutes before a subsequent relaxation. Compared with the ischemia–reperfusion group, an intravenous injection of p75ECD (3 mg/kg) 5 minutes before reperfusion reduced the myocardial infarct area at 24 hours after reperfusion (by triphenyltetrazolium chloride, 44.9±3.9% versus 34.6±5.7%, P

Background The role of platelets in the development of vascular inflammation and endothelial dysfunction in the pathogenesis of hypertension is well established at this time. Aspirin is known to relieve pain, decrease fever, reduce inflammation, impair platelet aggregation, and prevent clotting, yet its effect in the context of salt‐sensitive hypertension remains unclear. The present study investigated the importance of aspirin in inhibiting the abnormal activation of platelets and promoting the normal function of the vascular endothelium in a rat model of salt‐sensitive hypertension. Method and Results Dahl salt‐sensitive rats and salt‐resistant rats were fed a normal‐salt diet (4% NaCl), a high‐salt diet (8% NaCl), or a high‐salt diet with aspirin gavage (10 mg/kg per day) for 8 weeks. Blood pressure, platelet activation, vascular function, inflammatory response, and potential mechanism were measured. Low‐dose aspirin (10 mg/kg per day) decreased the high‐salt diet–induced elevation of blood pressure, platelet activation, leukocyte infiltration, and leukocyte–platelet aggregation (CD45+CD61+), as well as vascular endothelial and renal damage. These effects were related to the ability of aspirin to prevent the adhesion of leukocytes to endothelial cells via inhibition of the platelet cyclooxygenase 1 but not the cyclooxygenase 2 pathway. Aspirin also reversed the high‐salt diet–induced abnormal activation of complement and coagulation cascades in platelets. Conclusions These results highlight a new property of aspirin in ameliorating vascular endothelial dysfunction induced by platelet activation, which may be beneficial in the treatment of salt‐sensitive hypertension.

For moving ship detection in synthetic aperture radar (SAR) images, ship wakes on the sea surface may be detectable, thus leading to interferences in reconnaissance. To address this issue, a wake region detection approach by using multi-feature recombination and area-based morphological analysis is proposed with along-track interferogram-SAR systems. This approach aims to detect the near-ship wake region that is nearby a ship's hull and between two kelvin cusp lines. A novel test is constructed by recombining magnitude, phase, and the local variance of phase in the complex multi-look interferometric SAR image to detect the potential pixels of the ship wakes. Then, with a clustering algorithm based on the proposed test and the pixel spatial distance, the potential wake regions are acquired, and the real ones having sufficiently large areas can be accurately determined. Finally, experimental results on the TerraSAR-X dataset validate the effectiveness of the proposed method.

For the problem of the direction-of-arrival (DOA) and source number estimations with coexisting strong and weak signals, a new method for robust estimations of DOA and the number of sources based on an optimized broad band sparse array is proposed. To reduce the impact of the strong signals on the weak ones, an orthogonal projection matrix is constructed by the robust steering vector of the current strongest signal. The proposed method has super-resolution and is robust to array mismatch. The effectiveness of the proposed method is demonstrated by the results of simulations.