Coronary arteries bring blood flow to the heart muscle. Understanding the developmental program of the coronary arteries provides insights into the treatment of coronary artery diseases. Multiple sources have been described as contributing to coronary arteries including the proepicardium, sinus venosus (SV), and endocardium. However, the developmental origins of coronary vessels are still under intense study. We have produced a new genetic tool for studying coronary development, an AplnCreER mouse line, which expresses an inducible Cre recombinase specifically in developing coronary vessels. Quantitative analysis of coronary development and timed induction of AplnCreER fate tracing showed that the progenies of subepicardial endothelial cells (ECs) both invade the compact myocardium to form coronary arteries and remain on the surface to produce veins. We found that these subepicardial ECs are the major sources of intramyocardial coronary vessels in the developing heart. In vitro explant assays indicate that the majority of these subepicardial ECs arise from endocardium of the SV and atrium, but not from ventricular endocardium. Clonal analysis of Apln-positive cells indicates that a single subepicardial EC contributes equally to both coronary arteries and veins. Collectively, these data suggested that subepicardial ECs are the major source of intramyocardial coronary arteries in the ventricle wall, and that coronary arteries and veins have a common origin in the developing heart.

BackgroundUrinary Kidney Injury Molecule 1 (KIM-1) is a proximal tubular injury biomarker for early detection of acute kidney injury (AKI), with variable performance characteristics depending on clinical and population settings.MethodsMeta-analysis was performed to assess the diagnostic value of urinary KIM-1 in AKI. Relevant studies were searched from MEDLINE, EMBASE, Pubmed, Elsevier Science Direct, Scopus, Web of Science, Google Scholar and Cochrane Library. Meta-analysis methods were used to pool sensitivity and specificity and to construct summary receiver operating characteristic (SROC) curves.ResultsA total of 2979 patients from 11 eligible studies were enrolled in the analysis. Five prospective cohorts, two cross-sectional and four case-control studies were identified for meta-analysis. The estimated sensitivity of urinary KIM-1 for the diagnosis of AKI was 74.0% (95% CI, 61.0%–84.0%), and specificity was 86.0% (95% CI, 74.0%–93.0%). The SROC analysis showed an area under the curve of 0.86(0.83–0.89). Subgroup analysis suggested that population settings and detection time were the key factors affecting the efficiency of KIM-1 for AKI diagnosis.LimitationVarious population settings, different definition of AKI and Serum creatinine level used as the standard might have influence on AKI diagnosis. The relatively small number of studies and heterogeneity between them also affected the evaluation.ConclusionUrinary KIM-1 may be a promising biomarker for early detection of AKI with considerable predictive value, especially for cardiac surgery patients, and its potential value needs to be validated in large studies and across a broader scope of clinical settings.

Based on mean field calculations with Skyrme interactions, we extract a constraint on the isovector effective mass in nuclear matter at saturation density ρ0, i.e., m * v (ρ0) = (0.77±0.03)m by combining the experimental data of the centroid energy of the isovector giant dipole resonance (IVGDR) and the electric dipole polarizability αD in 208 Pb. Meanwhile, the isoscalar effective mass at ρ0 is determined to be m * s (ρ0) = (0.91 ± 0.05)m by analyzing the measured excitation energy of the isoscalar giant quadrupole resonance (ISGQR) in 208 Pb. From the constrained m * s (ρ0) and m * v (ρ0), we obtain the isospin splitting of nucleon effective mass in asymmetric nuclear matter of isospin asymmetry δ at ρ0 as [m * n (ρ0, δ) − m * p (ρ0, δ)]/m = ∆m * 1 (ρ0)δ + O(δ 3 ) with the linear isospin splitting coefficient ∆m * 1 (ρ0) = 0.33±0.16. We notice that using the recently corrected data on the αD in 208 Pb with the contribution of the quasideuteron effect subtracted slightly enhances the isovector effective mass to m * v (ρ0) = (0.80±0.03)m and reduces the linear isospin splitting coefficient to ∆m * 1 (ρ0) = 0.27±0.15. Furthermore, the constraints on m * v (ρ), m * s (ρ) and ∆m * 1 (ρ) at other densities are obtained from the similar analyses and we find that the ∆m * 1 (ρ) increases with the density.

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