Shear stress regulation of miR-93 and miR-484 maturation through nucleolin.

Pulsatile shear (PS) and oscillatory shear (OS) elicit distinct mechanotransduction signals that maintain endothelial homeostasis or induce endothelial dysfunction, respectively. A subset of microRNAs (miRs) in vascular endothelial cells (ECs) are differentially regulated by PS and OS, but the regulation of the miR processing and its implications in EC biology by shear stress are poorly understood. From a systematic in silico analysis for RNA binding proteins that regulate miR processing, we found that nucleolin (NCL) is a major regulator of miR processing in response to OS and essential for the maturation of miR-93 and miR-484 that target mRNAs encoding Krüppel-like factor 2 (KLF2) and endothelial nitric oxide synthase (eNOS). Additionally, anti-miR-93 and anti-miR-484 restore KLF2 and eNOS expression and NO bioavailability in ECs under OS. Analysis of posttranslational modifications of NCL identified that serine 328 (S328) phosphorylation by AMP-activated protein kinase (AMPK) was a major PS-activated event. AMPK phosphorylation of NCL sequesters it in the nucleus, thereby inhibiting miR-93 and miR-484 processing and their subsequent targeting of KLF2 and eNOS mRNA. Elevated levels of miR-93 and miR-484 were found in sera collected from individuals afflicted with coronary artery disease in two cohorts. These findings provide translational relevance of the AMPK-NCL-miR-93/miR-484 axis in miRNA processing in EC health and coronary artery disease

A data analysis method for isochronous mass spectrometry using two time-of-flight detectors at CSRe

The concept of isochronous mass spectrometry (IMS) applying two time-of-flight (TOF) detectors originated many years ago at GSI. However, the corresponding method for data analysis has never been discussed in detail. Recently, two TOF detectors have been installed at CSRe and the new working mode of the ring is under test. In this paper, a data analysis method for this mode is introduced and tested with a series of simulations. The results show that the new IMS method can significantly improve mass resolving power via the additional velocity information of stored ions. This improvement is especially important for nuclides with Lorentz factor $\gamma$-value far away from the transition point $\gamma _t$ of the storage ring CSRe.Comment: published in Chinese Physics C Vol. 39, No. 10 (2015) 10620

Stellar Atmospheric Parameters of M-type Stars from LAMOST DR8

© 2022. The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/The Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) Low Resolution Spectroscopic Survey (LRS) provides massive spectroscopic data of M-type stars, and the derived stellar parameters could bring vital help to various studies. We adopt the ULySS package to perform $\chi^2$ minimization with model spectra generated from the MILES interpolator, and determine the stellar atmospheric parameters for the M-type stars from LAMOST LRS Data Release (DR) 8. Comparison with the stellar parameters from APOGEE Stellar Parameter and Chemical Abundance Pipeline (ASPCAP) suggests that most of our results have good consistency. For M dwarfs, we achieve dispersions better than 74 K, 0.19 dex and 0.16 dex for $T_{\rm eff}$, $\log{g}$ and [Fe/H], while for M giants, the internal uncertainties are 58 K, 0.32 dex and 0.26 dex, respectively. Compared to ASPCAP we also find a systematic underestimation of $\Delta {T_{\rm eff}} =$ $-$176 K for M dwarfs, and a systematic overestimation of $\Delta {\log{g}} =$ 0.30 dex for M giants. However, such differences are less significant when we make comparison with common stars from other literature, which indicates that systematic biases exist in the difference of ASPCAP and other measurements. A catalog of 763,136 spectra corresponding to 616,314 M-type stars with derived stellar parameters is presented. We determine the stellar parameters for stars with $T_{\rm eff}$ higher than 2,900 K, with $\log{g}$ from -0.24 dex to 5.9 dex. The typical precisions are 45 K, 0.25 dex and 0.22 dex, for $T_{\rm eff}$, $\log{g}$ and [Fe/H], respectively, which are estimated from the duplicate observations of the same stars.Peer reviewe

Orphan Nuclear Receptor Nur77 Inhibits Cardiac Hypertrophic Response to Beta-Adrenergic Stimulation.

The orphan nuclear receptor Nur77 plays critical roles in cardiovascular diseases, and its expression is markedly induced in the heart after beta-adrenergic receptor (β-AR) activation. However, the functional significance of Nur77 in β-AR signaling in the heart remains unclear. By using Northern blot, Western blot, and immunofluorescent staining assays, we showed that Nur77 expression was markedly upregulated in cardiomyocytes in response to multiple hypertrophic stimuli, including isoproterenol (ISO), phenylephrine (PE), and endothelin-1 (ET-1). In a time- and dose-dependent manner, ISO increases Nur77 expression in the nuclei of cardiomyocytes. Overexpression of Nur77 markedly inhibited ISO-induced cardiac hypertrophy by inducing nuclear translocation of Nur77 in cardiomyocytes. Furthermore, cardiac overexpression of Nur77 by intramyocardial injection of Ad-Nur77 substantially inhibited cardiac hypertrophy and ameliorated cardiac dysfunction after chronic infusion of ISO in mice. Mechanistically, we demonstrated that Nur77 functionally interacts with NFATc3 and GATA4 and inhibits their transcriptional activities, which are critical for the development of cardiac hypertrophy. These results demonstrate for the first time that Nur77 is a novel negative regulator for the β-AR-induced cardiac hypertrophy through inhibiting the NFATc3 and GATA4 transcriptional pathways. Targeting Nur77 may represent a potentially novel therapeutic strategy for preventing cardiac hypertrophy and heart failure

Examine the species and beam-energy dependence of particle spectra using Tsallis Statistics

Tsallis Statistics was used to investigate the non-Boltzmann distribution of particle spectra and their dependence on particle species and beam energy in the relativistic heavy-ion collisions at SPS and RHIC. Produced particles are assumed to acquire radial flow and be of non-extensive statistics at freeze-out. J/psi and the particles containing strangeness were examined separately to study their radial flow and freeze-out. We found that the strange hadrons approach equilibrium quickly from peripheral to central A+A collisions and they tend to decouple earlier from the system than the light hadrons but with the same final radial flow. These results provide an alternative picture of freeze-outs: a thermalized system is produced at partonic phase; the hadronic scattering at later stage is not enough to maintain the system in equilibrium and does not increase the radial flow of the copiously produced light hadrons. The J/psi in Pb+Pb collisions at SPS is consistent with early decoupling and obtains little radial flow. The J/psi spectra at RHIC are also inconsistent with the bulk flow profile.Comment: 12 pages, 4 figures, added several references and some clarifications et

Outcomes of resection for colorectal cancer hepatic metastases stratified by evolving eras of treatment

<p>Abstract</p> <p>Background and purpose</p> <p>The outcomes and management of colorectal cancer (CRC) hepatic metastasis have undergone many evolutionary changes. In this study, we aimed to analyze the outcomes of patients with CRC hepatic metastasis in terms of the era of treatment.</p> <p>Methods</p> <p>We conducted a retrospective review of 279 patients who underwent liver resection (LR) for CRC hepatic metastases. The prognoses of patients treated pre-2003 (era 1) and post-2003 (era 2) were examined.</p> <p>Results</p> <p>Of the patients included in the study, 210 (75.3%) had CRC recurrence after LR. There was a significant difference in the ratio of CRC recurrence between the 2 eras (82.0% in era 1 <it>vs</it>. 69.5% in era 2; <it>p </it>= 0.008). Analysis of recurrence-free and overall survival rates also showed that the patient outcome was significantly better in the post-2003 era than in the pre-2003 era. Further analysis showed that a significantly higher percentage of patients in era 2 had received modern chemotherapeutic regimens including irinotecan and oxaliplatin, while patients in era 1 were mainly administered fluorouracil and leucovorin for adjuvant chemotherapy. Among patients with CRC recurrence, a significant ratio of those in era 2 underwent surgical resection for recurrent lesions, and these patients had a better survival curve than did patients without resection (34.1% <it>vs</it>. 2.2% for 5-year survival; <it>p </it>< 0.0001).</p> <p>Conclusion</p> <p>The incidence of CRC recurrence after LR for hepatic metastasis remains very high. However, the management and outcomes of patients with CRC hepatic metastasis have greatly improved with time, suggesting that the current use of aggressive multimodality treatments including surgical resection combined with modern chemotherapeutic regimens effectively prolongs the life expectancy of these patients.</p