Nuclear receptors in vascular biology

Nuclear receptors sense a wide range of steroids and hormones (estrogens, progesterone, androgens, glucocorticoid, and mineralocorticoid), vitamins (A and D), lipid metabolites, carbohydrates, and xenobiotics. In response to these diverse but critically important mediators, nuclear receptors regulate the homeostatic control of lipids, carbohydrate, cholesterol, and xenobiotic drug metabolism, inflammation, cell differentiation and development, including vascular development. The nuclear receptor family is one of the most important groups of signaling molecules in the body and as such represent some of the most important established and emerging clinical and therapeutic targets. This review will highlight some of the recent trends in nuclear receptor biology related to vascular biology

Time Distribution of the Onset of Chest Pain in Subjects with Acute ST-Elevation Myocardial Infarction: An Eight-Year, Single-Center Study in China

Objective: The objective of this study was to explore the time distribution patterns of the onset of chest pain in subjects with acute ST-elevation myocardial infarction in a Chinese population. Methods: A total of 1467 patients with acute ST-elevation myocardial infarction were enrolled from 2003 to 2010. The hourly, daily, monthly, seasonal and day-of-week fluctuations in the prevalence of acute ST-elevation myocardial infarction were analyzed. Results: A peak was found between the morning hours of 07:31 and 08:30. A second peak was observed between 14:31 and 15:30, and a third peak was found between 23:31 and 00:30 (p,0.001). The monthly maximum was recorded in November and the minimum was in April (p,0.001). The number of daily cases was greatest in autumn and lowest in the spring (p = 0.001). Day-of-the-week variations of ST-elevation acute myocardial infarction were not found, except in patients more than 75-years-old. Conclusions: Periodic variations in the frequency of ST-elevation acute myocardial infarction in Chinese patients showed significant differences with regard to diurnal, monthly and seasonal patterns. The exact mechanisms underlying thes

Local Difference Measures between Complex Networks for Dynamical System Model Evaluation

Acknowledgments We thank Reik V. Donner for inspiring suggestions that initialized the work presented herein. Jan H. Feldhoff is credited for providing us with the STARS simulation data and for his contributions to fruitful discussions. Comments by the anonymous reviewers are gratefully acknowledged as they led to substantial improvements of the manuscript.Peer reviewedPublisher PD

FAST observations of an extremely active episode of FRB 20201124A: IV. Spin Period Search

We report the properties of more than 800 bursts detected from the repeating fast radio burst (FRB) source FRB 20201124A with the Five-hundred-meter Aperture Spherical radio telescope (FAST) during an extremely active episode on UTC September 25th-28th, 2021 in a series of four papers. In this fourth paper of the series, we present a systematic search of the spin period and linear acceleration of the source object from both 996 individual pulse peaks and the dedispersed time series. No credible spin period was found from this data set. We rule out the presence of significant periodicity in the range between 1 ms to 100 s with a pulse duty cycle $< 0.49\pm0.08$ (when the profile is defined by a von-Mises function, not a boxcar function) and linear acceleration up to $300$ m s$^{-2}$ in each of the four one-hour observing sessions, and up to $0.6$ m s$^{-2}$ in all 4 days. These searches contest theoretical scenarios involving a 1 ms to 100 s isolated magnetar/pulsar with surface magnetic field $<10^{15}$ G and a small duty cycle (such as in a polar-cap emission mode) or a pulsar with a companion star or black hole up to 100 M$_{\rm \odot}$ and $P_b>10$ hours. We also perform a periodicity search of the fine structures and identify 53 unrelated millisecond-timescale "periods" in multi-components with the highest significance of 3.9 $\sigma$. The "periods" recovered from the fine structures are neither consistent nor harmonically related. Thus they are not likely to come from a spin period. We caution against claiming spin periodicity with significance below $\sim$ 4 $\sigma$ with multi-components from one-off FRBs. We discuss the implications of our results and the possible connections between FRB multi-components and pulsar micro-structures.Comment: Accepted by Research in Astronomy and Astrophysics (RAA

Scintillation Arc from FRB 20220912A

We present the interstellar scintillation analysis of fast radio burst (FRB) 20220912A during its extremely active episode in 2022 using data from the Five-hundred-meter Aperture Spherical Radio Telescope (FAST). We detect a scintillation arc in the FRB's secondary spectrum, which describes the power in terms of the scattered FRB signals' time delay and Doppler shift. The arc indicates that the scintillation is caused by a highly localized region of the ionized interstellar medium (IISM). Our analysis favors a Milky Way origin for the localized scattering medium but cannot rule out a host galaxy origin. We present our method for detecting the scintillation arc, which can be applied generally to sources with irregularly spaced bursts or pulses. These methods could help shed light on the complex interstellar environment surrounding the FRBs and in our Galaxy.Comment: SCIENCE CHINA Physics, Mechanics & Astronomy , Volume 67, Issue 1: 219512 (2024

Bicyclic triterpenoid Iripallidal induces apoptosis and inhibits Akt/mTOR pathway in glioma cells

<p>Abstract</p> <p>Background</p> <p>The highly resistant nature of glioblastoma multiforme (GBM) to chemotherapy prompted us to evaluate the efficacy of bicyclic triterpenoid Iripallidal against GBM in vitro.</p> <p>Methods</p> <p>The effect of Iripallidal on proliferation and apoptosis in glioma cell lines was evaluated by MTS, colony formation and caspase-3 activity. The effect of iripallidal to regulate (i) Akt/mTOR and STAT3 signaling (ii) molecules associated with cell cycle and DNA damage was evaluated by Western blot analysis. The effect of Iripallidal on telomerase activity was also determined.</p> <p>Results</p> <p>Iripallidal (i) induced apoptosis, (ii) inhibited Akt/mTOR and STAT3 signaling, (iii) altered molecules associated with cell cycle and DNA damage, (iv) inhibited telomerase activity and colony forming efficiency of glioma cells. In addition, Iripallidal displayed anti-proliferative activity against non-glioma cancer cell lines of diverse origin.</p> <p>Conclusion</p> <p>The ability of Iripallidal to serve as a dual-inhibitor of Akt/mTOR and STAT3 signaling warrants further investigation into its role as a therapeutic strategy against GBM.</p

Identification of Enriched Driver Gene Alterations in Subgroups of Non-Small Cell Lung Cancer Patients Based on Histology and Smoking Status

BACKGROUND: Appropriate patient selection is needed for targeted therapies that are efficacious only in patients with specific genetic alterations. We aimed to define subgroups of patients with candidate driver genes in patients with non-small cell lung cancer. METHODS: Patients with primary lung cancer who underwent clinical genetic tests at Guangdong General Hospital were enrolled. Driver genes were detected by sequencing, high-resolution melt analysis, qPCR, or multiple PCR and RACE methods. RESULTS: 524 patients were enrolled in this study, and the differences in driver gene alterations among subgroups were analyzed based on histology and smoking status. In a subgroup of non-smokers with adenocarcinoma, EGFR was the most frequently altered gene, with a mutation rate of 49.8%, followed by EML4-ALK (9.3%), PTEN (9.1%), PIK3CA (5.2%), c-Met (4.8%), KRAS (4.5%), STK11 (2.7%), and BRAF (1.9%). The three most frequently altered genes in a subgroup of smokers with adenocarcinoma were EGFR (22.0%), STK11 (19.0%), and KRAS (12.0%). We only found EGFR (8.0%), c-Met (2.8%), and PIK3CA (2.6%) alterations in the non-smoker with squamous cell carcinoma (SCC) subgroup. PTEN (16.1%), STK11 (8.3%), and PIK3CA (7.2%) were the three most frequently enriched genes in smokers with SCC. DDR2 and FGFR2 only presented in smokers with SCC (4.4% and 2.2%, respectively). Among these four subgroups, the differences in EGFR, KRAS, and PTEN mutations were statistically significant. CONCLUSION: The distinct features of driver gene alterations in different subgroups based on histology and smoking status were helpful in defining patients for future clinical trials that target these genes. This study also suggests that we may consider patients with infrequent alterations of driver genes as having rare or orphan diseases that should be managed with special molecularly targeted therapies

FAST observations of an extremely active episode of FRB 20201124A: III. Polarimetry

As the third paper in the multiple-part series, we report the statistical properties of radio bursts detected from the repeating fast radio burst (FRB) source FRB 20201124A with the Five-hundred-meter Aperture Spherical radio telescope (FAST) during an extremely active episode between the 25th and the 28th of September 2021 (UT). We focus on the polarisation properties of 536 bright bursts with $\mathrm{S/N}>50$. We found that the Faraday rotation measures (RMs) monotonically dropped from $-579 \ {\rm rad \ m^{-2}}$ to $-605 \ {\rm rad \ m^{-2}}$ in the 4-day window. The RM values were compatible with the values ($-300$ to $-900\ {\rm rad \ m^{-2}}$ ) reported 4 month ago (Xu et al. 2022). However, the RM evolution rate in the current observation window was at least an order of magnitude smaller than the one ($\sim 500\ {\rm rad \ m^{-2}\, day^{-1}}$) previously reported during the rapid RM-variation phase, but is still higher than the one ($\le 1\ {\rm rad \ m^{-2} day^{-1}}$) during the later RM no-evolution phase. The bursts of FRB 20201124A were highly polarised with the total degree of polarisation (circular plus linear) greater than 90polarisation position angles (PAs), degree of linear polarisation ($L/I$), and degree of circular polarisation ($V/I$) can be characterised with unimodal distribution functions. During the observation window, the distributions became wider with time, i.e. with larger scatter, but the centroids of the distribution functions remained nearly constant. For individual bursts, significant PA variations (confidence level 5-$\sigma$) were observed in 33% of all bursts. The polarisation of single pulses seems to follow certain complex trajectories on the Poincar\'e sphere, which may shed light on the radiation mechanism at the source or the plasma properties along the path of FRB propagation.Comment: 25 pages, 16 figures. Accepted by Research in Astronomy and Astrophysics (RAA

Genetic Polymorphism in a VEGF-Independent Angiogenesis Gene ANGPT1 and Overall Survival of Colorectal Cancer Patients after Surgical Resection

Background The VEGF-independent angiogenic signaling plays an important role in the development of colorectal cancer (CRC). However, its implication in the clinical outcome of CRC has not been reported. This study aimed to investigate the association between genetic variations in several major VEGF-independent signaling pathway genes and the overall survival of CRC patients. Methods Seven single nucleotide polymorphisms (SNPs) in four important VEGF-independent angiogenic genes (ANGPT1, AMOT, DLL4 and ENG) were genotyped in a Chinese population with 408 CRC patients. Results One SNP, rs1954727 in ANGPT1, was significantly associated with CRC overall survival. Compared to patients with the homozygous wild-type genotype of rs1954727, those with heterozygous and homozygous variant genotypes exhibited a favorable overall survival with a hazard ratio (HR) of 0.89 (95% confidence interval [CI] 0.55–1.43, P = 0.623), and 0.32 (95% CI 0.15–0.71, P = 0.005), respectively (P trend = 0.008). In stratified analysis, this association remained significant in patients receiving chemotherapy (P trend = 0.012), but not in those without chemotherapy. We further evaluated the effects of chemotherapy on CRC survival that was stratified by rs1954727 genotypes. We found that chemotherapy resulted in a significantly better overall survival in the CRC patients (HR = 0.44, 95% CI 0.26–0.75, P = 0.002), which was especially prominent in those patients with the heterozygous genotype of rs1954727 (HR = 0.45, 95%CI 0.22–0.92, P = 0.028). Conclusion Our data suggest that rs1954727 in ANGPT1 gene might be a prognostic biomarker for the overall survival of CRC patients, especially in those receiving chemotherapy, a finding that warrants validation in larger independent populations