Protective effect of syringaresinol on rats with diabetic nephropathy via regulation of Nrf2/HO-1 and TGF- β1/Smads pathways

Purpose: To investigate the protective role of syringaresinol in a rat model of diabetic nephropathy (DN). Methods: Streptozotocin was injected intraperitoneally into rats to establish the diabetic model. Streptozotocin-induced rats were orally administered syringaresinol, and pathological changes in kidneys were assessed using hematoxylin and eosin staining. Enzyme-linked immunosorbent assay (ELISA) was used to determine kidney injury indicators, 24-h urine proteins, blood urea nitrogen (BUN), and serum creatinine (SCR). Blood glucose was measured using a blood glucose meter, while levels of malonaldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) in kidney were also measured using ELISA. Results: Pathological changes in the kidneys were observed in rats post-streptozotocin treatment. Administration of syringaresinol reduced the lesion degree, with improved pathological morphology in kidney. Syringaresinol administration significantly attenuated streptozotocin-increased levels of BUN, SCR, 24-h urine protein, and blood glucose (p < 0.01). Streptozotocin-induced oxidative stress, shown by enhanced MDA level and reduced levels of SOD, CAT, and GSH-PX, was reversed in rat kidneys following syringaresinol administration. However, the expression levels of nuclear factor erythropoietin- 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) proteins decreased, while transforming growth factor-beta 1 (TGF-β1) and signal transducer and transcriptional modulator (Smad) 2/3/7 proteins increased in rats post-streptozotocin treatment. Syringaresinol administration reversed the effects of streptozotocin on protein expression of Nrf2, HO-1, TGF-β1, and Smad 2/3/7. Conclusion: Syringaresinol exerted a protective effect against DN through activation of Nrf2 and inactivation of TGF-β1/Smad pathways. Thus, the compound can potentially be developed for management of diabetic nephropathy

Semilocal convergence analysis of an eighth order iterative method for solving nonlinear systems

In this paper, the semilocal convergence of the eighth order iterative method is proved in Banach space by using the recursive relation, and the proof process does not need high order derivative. By selecting the appropriate initial point and applying the Lipschitz condition to the first order Fréchet derivative in the whole region, the existence and uniqueness domain are obtained. In addition, the theoretical results of semilocal convergence are applied to two nonlinear systems, and satisfactory results are obtained

Sea Level Pressure Variability Over the Southern Indian Ocean Inferred from a Glaciochemical Record in Princess Elizabeth Land, East Antarctica

A 250-year, high-resolution, multivariate ice core record from LGB65 (70degrees50\u2707 S, 77degrees04\u2729 E; 1850 m asl), Princess Elizabeth Land (PEL), is used to investigate sea level pressure (SLP) variability over the southern Indian Ocean (SIO). Empirical orthogonal function (EOF) analysis reveals that the first EOF (EOF1) of the glaciochemical record from LGB65 represents most of the variability in sea salt throughout the 250-year record. EOF1 is negatively correlated (95% confidence level and higher) to instrumental mean sea level pressure (MSLP) at Kerguelen and New Amsterdam islands, SIO. On the basis of comparison with NCEP/NCAR reanalysis, strong correlations were found between sea-salt variations and a quasi-stationary low that lies to the north of Prydz Bay, SIO. Comparison with a 250-year-long summer transpolar index (STPI) inferred from sub-Antarctic tree ring records reveals strong coherency. Decadal-scale SLP variability over SIO suggests shifting of the polar vortex. Prominent decadal-scale deepening of the southern Indian Ocean low (SIOL) exists circa 1790, 1810, 1835, 1860, 1880, 1900, and 1940 A. D., continuously after the 1970s, and prominent weakening circa 1750, 1795, 1825, 1850, 1870, 1890, 1910, and 1955 A. D. The LGB65 sea-salt record is characterized by significant decadal-scale variability with a strong similar to21-year periodic structure (99.9% confidence level). The relationship between LGB65 sea salt and solar irradiance changes shows that this periodicity is possibly the solar Hale cycle ( 22 years)

Leveraging wearable sensors for human daily activity recognition with stacked denoising autoencoders

Activity recognition has received considerable attention in many research fields, such as industrial and healthcare fields. However, many researches about activity recognition have focused on static activities and dynamic activities in current literature, while, the transitional activities, such as stand-to-sit and sit-to-stand, are more difficult to recognize than both of them. Consider that it may be important in real applications. Thus, a novel framework is proposed in this paper to recognize static activities, dynamic activities, and transitional activities by utilizing stacked denoising autoencoders (SDAE), which is able to extract features automatically as a deep learning model rather than utilize manual features extracted by conventional machine learning methods. Moreover, the resampling technique (random oversampling) is used to improve problem of unbalanced samples due to relatively short duration characteristic of transitional activity. The experiment protocol is designed to collect twelve daily activities (three types) by using wearable sensors from 10 adults in smart lab of Ulster University, the experiment results show the significant performance on transitional activity recognition and achieve the overall accuracy of 94.88% on three types of activities. The results obtained by comparing with other methods and performances on other three public datasets verify the feasibility and priority of our framework. This paper also explores the effect of multiple sensors (accelerometer and gyroscope) to determine the optimal combination for activity recognition

Phosphorylation of ribosomal protein S6 confers PARP inhibitor resistance in BRCA1-deficient cancers

Inhibition of poly(ADP-ribose) polymerase (PARP) is a promising therapeutic strategy for BRCA1 deficient cancers, however, the development of drug resistance limits clinical efficacy. Previously we found that the BRCA1-AKT1 pathway contributes to tumorigenesis and that the AKT1/mTOR is a novel therapeutic target for BRCA1-deficient cancers. Here, we report that phosphorylation of ribosomal protein S6, a mTOR downstream effector, is greatly increased in BRCA1 deficient cells resistant to PARP inhibition. Phosphorylation of S6 is associated with DNA damage and repair signaling during PARP inhibitor treatment. In BRCA1 deficient cells, expression of S6 lacking all five phosphorylatable sites renders the cells sensitive to PARP inhibitor and increases DNA damage signals. In addition, the S6 mutations reduce tumor formation induced by Brca1-deficiency in mice. Inhibition of S6 phosphorylation by rapamycin restores PARP sensitivity to resistant cells. Combined treatment with rapamycin and PARP inhibitor effectively suppresses BRCA1-deficient tumor growth in mice. These results provide evidence for a novel mechanism by which BRCA1 deficient cancers acquire drug resistance and suggest a new therapeutic strategy to circumvent resistance

A novel porcine reproductive and respiratory syndrome virus vector system that stably expresses enhanced green fluorescent protein as a separate transcription unit

Abstract Here we report the rescue of a recombinant porcine reproductive and respiratory syndrome virus (PRRSV) carrying an enhanced green fluorescent protein (EGFP) reporter gene as a separate transcription unit. A copy of the transcription regulatory sequence for ORF6 (TRS6) was inserted between the N protein and 3′-UTR to drive the transcription of the EGFP gene and yield a general purpose expression vector. Successful recovery of PRRSV was obtained using an RNA polymerase II promoter to drive transcription of the full-length virus genome, which was assembled in a bacterial artificial chromosome (BAC). The recombinant virus showed growth replication characteristics similar to those of the wild-type virus in the infected cells. In addition, the recombinant virus stably expressed EGFP for at least 10 passages. EGFP expression was detected at approximately 10 h post infection by live-cell imaging to follow the virus spread in real time and the infection of neighbouring cells occurred predominantly through cell-to-cell-contact. Finally, the recombinant virus generated was found to be an excellent tool for neutralising antibodies and antiviral compound screening. The newly established reverse genetics system for PRRSV could be a useful tool not only to monitor virus spread and screen for neutralising antibodies and antiviral compounds, but also for fundamental research on the biology of the virus.This study was funded by grants from the National Natural Science Foundation of China (U0931003/L01) and the National High-Tech R&D Program of China (2011AA10A208) to EMZ, the National Natural Science Foundation of China (31302103) to WCB, the European Community’s Seventh Frame-work Programme (PoRRSCon, FP7-KBBE-2009-3-245141) and the Ministry of Science and Innovation of Spain (MCINN) (BIO2010-16075) to FA and LE.Peer Reviewe

Single longitudinal mode narrow linewidth thulium-doped fiber laser based on an eye-shaped dual-ring filter

A single-longitudinal-mode (SLM) thulium-doped fiber laser, based on an eye-shaped passive dual-ring filter, is designed and constructed. The eye-shaped passive compound cavity consisting of four couplers is used to increase the longitudinal mode spacing, and its performance is numerically analyzed in detail. A homemade uniform fiber Bragg grating serves as a wavelength selection device and a saturable absorber is used to further suppress the intense longitudinal mode competition in the laser cavity, ensuring the single-longitudinal-mode output. The experimental results demonstrate a laser output with a center wavelength of 2,049.85 nm and an optical signal-to-noise ratio of 63 dB. Moreover, the power fluctuation is less than 0.6 dB, and the center wavelength fluctuation is less than 0.03 nm over a continuous measurement period of 60 min, demonstrating an excellent stability. The laser linewidth is measured using an unbalanced Michelson interferometer and β-separation line method, resulting in a linewidth of 11.22 kHz

HIV Screening and Awareness Survey for Pregnant Women in a Remote Area in Xinjiang Uyghur Autonomous Region of China

Objective: The number of people infected with human immunodeficiency virus (HIV) in China has increased in recent years. HIV screening for pregnant women was performed in a remote area in Xinjiang, as an effort to promote universal HIV screening in pregnant women and to help prevention of mother-to-child transmission. Methods: Pregnant women in Burqin and Jeminay Counties in Xinjiang were offered free voluntary HIV screening. Local mid-level medical workers were trained to use Determine® HIV-1/2 kit for HIV screening. All the tested pregnant women signed a consent form, received HIV education material, and participated in an HIV knowledge survey. Results: All the 890 pregnant women receiving HIV test had negative result. Among these women, 67.6% were Kazakh and 40.9% were farmers. Survey of HIV knowledge showed that these women's awareness about mother-to-child transmission was limited. The levels of HIV knowledge were related with ethnic background, age, education and profession of the pregnant women. Conclusion: The results suggested that HIV infection had not become a significant problem among the pregnant women in this remote area of Xinjiang, but continued efforts to improve the awareness of HIV, especially the knowledge about mother-to-child transmission of HIV, in pregnant women were needed

SIRT1 Functions as an Important Regulator of Estrogen-Mediated Cardiomyocyte Protection in Angiotensin II-Induced Heart Hypertrophy

Background. Sirtuin 1 (SIRT1) is a member of the sirtuin family, which could activate cell survival machinery and has been shown to be protective in regulation of heart function. Here, we determined the mechanism by which SIRT1 regulates Angiotensin II- (AngII-) induced cardiac hypertrophy and injury in vivo and in vitro. Methods. We analyzed SIRT1 expression in the hearts of control and AngII-induced mouse hypertrophy. Female C57BL/6 mice were ovariectomized and pretreated with 17β-estradiol to measure SIRT1 expression. Protein synthesis, cardiomyocyte surface area analysis, qRT-PCR, TUNEL staining, and Western blot were performed on AngII-induced mouse heart hypertrophy samples and cultured neonatal rat ventricular myocytes (NRVMs) to investigate the function of SIRT1. Results. SIRT1 expression was slightly upregulated in AngII-induced mouse heart hypertrophy in vivo and in vitro, accompanied by elevated cardiomyocyte apoptosis. SIRT1 overexpression relieves AngII-induced cardiomyocyte hypertrophy and apoptosis. 17β-Estradiol was able to protect cardiomyocytes from AngII-induced injury with a profound upregulation of SIRT1 and activation of AMPK. Moreover, estrogen receptor inhibitor ICI 182,780 and SIRT1 inhibitor niacinamide could block SIRT1’s protective effect. Conclusions. These results indicate that SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection during AngII-induced heart hypertrophy and injury