Molecular Cloning of the Genes Encoding the PR55/Bβ/δ Regulatory Subunits for PP-2A and Analysis of Their Functions in Regulating Development of Goldfish, Carassius auratus

The protein phosphatase-2A (PP-2A), one of the major phosphatases in eukaryotes, is a heterotrimer, consisting of a scaffold A subunit, a catalytic C subunit and a regulatory B subunit. Previous studies have shown that besides regulating specific PP-2A activity, various B subunits encoded by more than 16 different genes, may have other functions. To explore the possible roles of the regulatory subunits of PP-2A in vertebrate development, we have cloned the PR55/B family regulatory subunits: β and δ, analyzed their tissue specific and developmental expression patterns in Goldfish ( Carassius auratus). Our results revealed that the full-length cDNA for PR55/Bβ consists of 1940 bp with an open reading frame of 1332 nucleotides coding for a deduced protein of 443 amino acids. The full length PR55/Bδ cDNA is 2163 bp containing an open reading frame of 1347 nucleotides encoding a deduced protein of 448 amino acids. The two isoforms of PR55/B display high levels of sequence identity with their counterparts in other species. The PR55/Bβ mRNA and protein are detected in brain and heart. In contrast, the PR55/Bδ is expressed in all 9 tissues examined at both mRNA and protein levels. During development of goldfish, the mRNAs for PR55/Bβ and PR55/Bδ show distinct patterns. At the protein level, PR55/Bδ is expressed at all developmental stages examined, suggesting its important role in regulating goldfish development. Expression of the PR55/Bδ anti-sense RNA leads to significant downregulation of PR55/Bδ proteins and caused severe abnormality in goldfish trunk and eye development. Together, our results suggested that PR55/Bδ plays an important role in governing normal trunk and eye formation during goldfish development

Changes of outer retinal thickness with increasing age in normal eyes

AIM:To comprehensively investigate the relationship between outer retinal layer thickness and age in normal eyes.METHODS: One hundred normal eyes of 100 subjects who underwent spectral-domain optical coherence tomography(SD-OCT)were included in this retrospective study. The distances between the external limiting membrane(ELM)line and the photoreceptor inner segment/outer segment(IS/OS)line(ELM-IS/OS), the IS/OS line and the cone outer segment tips(COST)line(IS/OS-COST), the COST line and the retinal pigment epithelium(RPE)complex(COST-RPE)and the full retinal thickness(RT)were measured at the fovea and on four quarters. The relationship between thickness and age or sex was then analysed.RESULTS: A thinner RT was observed in women in a multiple regression analysis(men: 234.47±16.79 μm; women: 223.13±15.43 μm). The RT on the nasal quarter and the ELM-IS/OS thickness at the fovea and on the four quarters were significantly and negatively correlated with age. The IS/OS-COST and COST-RPE thicknesses at the fovea and on the four quarters were not significantly correlated with age or sex, respectively. The RT at the fovea was significantly thinner than on the four quarters. The ELM-IS/OS, IS/OS-COST and COST-RPE thicknesses at the fovea were significantly thicker than on the four quarters. CONCLUSION: In normal eyes, the RT thickness on the nasal quarter and the ELM-IS/OS thickness were significantly and negatively correlated with age. The IS/OS-COST and COST-RPE thicknesses were not significantly correlated with age or sex

The Role of Macrolide Antibiotics in Increasing Cardiovascular Risk

AbstractBackgroundLarge cohort studies provide conflicting evidence regarding the potential for oral macrolide antibiotics to increase the risk of serious cardiac events.ObjectivesThis study performed a meta-analysis to examine the link between macrolides and risk of sudden cardiac death (SCD) or ventricular tachyarrhythmias (VTA), cardiovascular death, and death from any cause.MethodsWe performed a search of published reports by using MEDLINE (January 1, 1966, to April 30, 2015) and EMBASE (January 1, 1980, to April 30, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included.ResultsThirty-three studies involving 20,779,963 participants were identified. Patients taking macrolides, compared with those who took no macrolides, experienced an increased risk of developing SCD or VTA (RR: 2.42; 95% CI: 1.61 to 3.63), SCD (RR: 2.52; 95% CI: 1.91 to 3.31), and cardiovascular death (RR: 1.31; 95% CI: 1.06 to 1.62). No association was found between macrolides use and all-cause death or any cardiovascular events. The RRs associated with SCD or VTA were 3.40 for azithromycin, 2.16 for clarithromycin, and 3.61 for erythromycin, respectively. RRs for cardiovascular death were 1.54 for azithromycin and 1.48 for clarithromycin. No association was noted between roxithromycin and adverse cardiac outcomes. Treatment with macrolides is associated with an absolute risk increase of 118.1 additional SCDs or VTA, and 38.2 additional cardiovascular deaths per 1 million treatment courses.ConclusionsAdministration of macrolide antibiotics is associated with increased risk for SCD or VTA and cardiovascular death but not increased all-cause mortality

CT radiomics model combined with clinical and radiographic features for discriminating peripheral small cell lung cancer from peripheral lung adenocarcinoma

PurposeExploring a non-invasive method to accurately differentiate peripheral small cell lung cancer (PSCLC) and peripheral lung adenocarcinoma (PADC) could improve clinical decision-making and prognosis.MethodsThis retrospective study reviewed the clinicopathological and imaging data of lung cancer patients between October 2017 and March 2022. A total of 240 patients were enrolled in this study, including 80 cases diagnosed with PSCLC and 160 with PADC. All patients were randomized in a seven-to-three ratio into the training and validation datasets (170 vs. 70, respectively). The least absolute shrinkage and selection operator regression was employed to generate radiomics features and univariate analysis, followed by multivariate logistic regression to select significant clinical and radiographic factors to generate four models: clinical, radiomics, clinical-radiographic, and clinical-radiographic-radiomics (comprehensive). The Delong test was to compare areas under the receiver operating characteristic curves (AUCs) in the models.ResultsFive clinical-radiographic features and twenty-three selected radiomics features differed significantly in the identification of PSCLC and PADC. The clinical, radiomics, clinical-radiographic and comprehensive models demonstrated AUCs of 0.8960, 0.8356, 0.9396, and 0.9671 in the validation set, with the comprehensive model having better discernment than the clinical model (P=0.036), the radiomics model (P=0.006) and the clinical–radiographic model (P=0.049).ConclusionsThe proposed model combining clinical data, radiographic characteristics and radiomics features could accurately distinguish PSCLC from PADC, thus providing a potential non-invasive method to help clinicians improve treatment decisions

High-speed measurement-device-independent quantum key distribution with integrated silicon photonics

Measurement-device-independent quantum key distribution (MDI-QKD) removes all detector side channels and enables secure QKD with an untrusted relay. It is suitable for building a star-type quantum access network, where the complicated and expensive measurement devices are placed in the central untrusted relay and each user requires only a low-cost transmitter, such as an integrated photonic chip. Here, we experimentally demonstrate a 1.25 GHz silicon photonic chip-based MDI-QKD system using polarization encoding. The photonic chip transmitters integrate the necessary encoding components for a standard QKD source. We implement random modulations of polarization states and decoy intensities, and demonstrate a finite-key secret rate of 31 bps over 36 dB channel loss (or 180 km standard fiber). This key rate is higher than state-of-the-art MDI-QKD experiments. The results show that silicon photonic chip-based MDI-QKD, benefiting from miniaturization, low-cost manufacture and compatibility with CMOS microelectronics, is a promising solution for future quantum secure networks.Comment: 30 pages, 12 figure

Apigenin Combined With Gefitinib Blocks Autophagy Flux and Induces Apoptotic Cell Death Through Inhibition of HIF-1α, c-Myc, p-EGFR, and Glucose Metabolism in EGFR L858R+T790M-Mutated H1975 Cells

Cancer cells are characterized by abnormally increased glucose uptake and active bio-energy and biosynthesis to support the proliferation, metastasis, and drug resistant survival. We examined the therapeutic value of the combination of apigenin (a natural small-molecule inhibitor of Glut1 belonging to the flavonoid family) and gefitinib on epidermal growth factor receptor (EGFR)-resistant mutant non-small cell lung cancer, to notably damage glucose utilization and thus suppress cell growth and malignant behavior. Here, we demonstrate that apigenin combined with gefitinib inhibits multiple oncogenic drivers such as c-Myc, HIF-1α, and EGFR, reduces Gluts and MCT1 protein expression, and inactivates the 5′ adenosine monophosphate-activated protein kinase (AMPK) signaling, which regulates glucose uptake and maintains energy metabolism, leading to impaired energy utilization in EGFR L858R-T790M-mutated H1975 lung cancer cells. H1975 cells exhibit dysregulated metabolism and apoptotic cell death following treatment with apigenin + gefitinib. Therefore, the combined apigenin + gefitinib treatment presents an attractive strategy as alternative treatment for the acquired resistance to EGFR-TKIs in NSCLC

Holographic dark energy in a universe with spatial curvature and massive neutrinos: a full Markov Chain Monte Carlo exploration

In this paper, we report the results of constraining the holographic dark energy model with spatial curvature and massive neutrinos, based on a Markov Chain Monte Carlo global fit technique. The cosmic observational data include the full WMAP 7-yr temperature and polarization data, the type Ia supernova data from Union2.1 sample, the baryon acoustic oscillation data from SDSS DR7 and WiggleZ Dark Energy Survey, and the latest measurements of $H_0$ from HST. To deal with the perturbations of dark energy, we adopt the parameterized post-Friedmann method. We find that, for the simplest holographic dark energy model without spatial curvature and massive neutrinos, the phenomenological parameter $c<1$ at more than $4\sigma$ confidence level. The inclusion of spatial curvature enlarges the error bars and leads to $c<1$ only in about $2.5\sigma$ range; in contrast, the inclusion of massive neutrinos does not have significant influence on $c$. We also find that, for the holographic dark energy model with spatial curvature but without massive neutrinos, the $3\sigma$ error bars of the current fractional curvature density $\Omega_{k0}$ are still in order of $10^{-2}$; for the model with massive neutrinos but without spatial curvature, the $2\sigma$ upper bound of the total mass of neutrinos is $\sum m_{\nu} < 0.48$ eV. Moreover, there exists clear degeneracy between spatial curvature and massive neutrinos in the holographic dark energy model, which enlarges the upper bound of $\sum m_{\nu}$ by more than 2 times. In addition, we demonstrate that, making use of the full WMAP data can give better constraints on the holographic dark energy model, compared with the case using the WMAP ``distance priors''.Comment: 21 pages, 10 figures; major revision; new figures and discussions added; accepted by JCA