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Background: Claudin-5, claudin-9, and claudin-11 are expressed in endothelial cells to constitute tight junctions, and their deficiency may lead to hyperpermeability, which is the initiating process and pathological basis of cardiovascular disease. Although tongxinluo (TXL) has satisfactory antianginal effects, whether and how it modulates claudin-5, claudin-9, and claudin-11 in hypoxia-stimulated human cardiac microvascular endothelial cells (HCMECs) have not been reported. Methods: In this study, HCMECs were stimulated with CoCl2to mimic hypoxia and treated with TXL. First, the messenger RNA (mRNA) expression of claudin-5, claudin-9, and claudin-11 was confirmed. Then, the protein content and distribution of claudin-9, as well as cell morphological changes were evaluated after TXL treatment. Furthermore, the distribution and content histone H3K9 acetylation (H3K9ac) in the claudin-9 gene promoter, which guarantees transcriptional activation, were examined to explore the underlying mechanism, by which TXL up-regulates claudin-9 in hypoxia-stimulated HCMECs. Results: We found that hypoxia-suppressed claudin-9 gene expression in HCMECs (F = 7.244; P = 0.011) and the hypoxia-suppressed claudin-9 could be reversed by TXL (F = 61.911; P = 0.000), which was verified by its protein content changes (F = 29.142; P = 0.000). Moreover, high-dose TXL promoted the cytomembrane localization of claudin-9 in hypoxia-stimulated HCMECs, with attenuation of cell injury. Furthermore, high-dose TXL elevated the hypoxia-inhibited H3K9ac in the claudin-9 gene promoter (F = 37.766; P = 0.000), activating claudin-9 transcription. Conclusions: The results manifested that TXL reversed the hypoxia-suppressed claudin-9 by elevating H3K9ac in its gene promoter, playing protective roles in HCMECs.

Background: Endothelial dysfunction is considered as the initiating process and pathological basis of cardiovascular disease. Cyclooxygenase-2 (COX-2) and prostacyclin synthase (PGIS), inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) are key enzymes with opposing actions in inflammation and oxidative stress, which are believed to be the major driver of endothelial dysfunction. And in hypoxia (Hx), Hx-inducible factor (HIF)-1α and HIF-2α are predominantly induced to activate vascular endothelial growth factor (VEGF), resulting in abnormal proliferation. Whether and how Tongxinluo (TXL) modulates COX-2, PGIS, iNOS, eNOS, HIF-1α, HIF-2α, and VEGF in Hx-stimulated human cardiac microvascular endothelial cells (HCMECs) have not been clarified. Methods: HCMEC were treated with CoCl 2 to mimic Hx and the mRNA expressions of COX-2, PGIS, iNOS, eNOS, HIF-1α, HIF-2α, and VEGF were first confirmed, and then their mRNA expression and protein content as well as the cell pathological alterations were evaluated for TXL treatment with different concentrations. In addition, the effector molecular of inflammation prostaglandin E 2 (PGE 2 ) and the oxidative marker nitrotyrosine (NT) was adopted to reflect HCMEC injury. Results: Hx could induce time-dependent increase of COX-2, iNOS, HIF-2α, and VEGF in HCMEC. Based on the Hx-induced increase, TXL could mainly decrease COX-2, iNOS, HIF-2α, and VEGF in a concentration-dependent manner, with limited effect on the increase of PGIS and eNOS. Their protein contents verified the mRNA expression changes, which was consistent with the cell morphological alterations. Furthermore, high dose TXL could inhibit the Hx-induced increase of PGE 2 and NT contents, attenuating the inflammatory and oxidative injury. Conclusions: TXL could inhibit inflammation-related COX-2, oxidative stress-related iNOS, and HIF-2α/VEGF to antagonize Hx-induced HCMEC injury.

Starting from more than 11,200 short-period (less than 0.5 days) EW-type eclipsing binary candidates with the All-Sky Automated Survey for Supernovae V -band light curves, we use the Markov Chain Monte Carlo algorithm and neural networks to obtain the mass ratio ( q ), orbital inclination ( incl ), fill-out factor ( f ), and temperature ratio ( T _s / T _p ). After crossmatching with the Gaia DR3 database, the final sample contains parameters of 2399 A-type and 8712 W-type contact binaries (CBs). We present the distributions of parameters of these 11,111 short-period CBs. The mass ratio ( q ) and fill-out factor ( f ) are found to obey log-normal distributions, and the remaining parameters obey normal distributions. There is a significant period–temperature correlation of these CBs. Additionally, the temperature ratio ( T _s / T _p ) tends to increase as the orbital period decreases for W-type CBs. There is no significant correlation between them for A-type CBs. The mass ratio and fill-out factor ( q − f ) diagram suggest there is no significant correlation between these two parameters. A clear correlation exists between the mass ratio and radius ratio. The radius ratio increases with the mass ratio. Moreover, the deep fill-out CBs tend to fall on the upper boundary of the q − R _s / R _p distribution, while the shallow fill-out CBs fall on the lower boundary.

In this paper, we use two methods, an algorithm of the density-based spatial clustering of applications with noise combined with the Gaussian mixture model, and the maximum likelihood method, to study two open clusters: IC 2488 and IC 2714 with Gaia Data Release 3 data. We compare the two methods in terms of cluster star number, isochrone fitting, cluster mass, and radius. The comparison shows that the selections of cluster stars by the two methods are consistent. The parameters obtained by the two methods are very close. But there are slight differences between the two methods for faint stars in IC 2714. The maximum likelihood method selects more faint stars outside of the main-sequence stripe. We conclude that the maximum likelihood method is more likely affected by field stars.