Activation of Orexin System Stimulates CaMKII Expression

Hyperactivity of the orexin system within the paraventricular nucleus (PVN) has been shown to contribute to increased sympathetic nerve activity (SNA) and blood pressure (BP) in rodent animals. However, the underlying molecular mechanisms remain unclear. Here, we test the hypothesis that orexin system activation stimulates calcium/calmodulin-dependent kinase II (CaMKII) expression and activation, and stimulation of CaMKII expressing PVN neurons increases SNA and BP. Real-time PCR and/or western blot were carried out to test the effect of orexin-A administration on CaMKII expression in the PVN of normal Sprague Dawley (SD) rats and orexin receptor 1 (OX1R) expressing PC12 cells. Immunostaining was performed to assess OX1R cellular localization in the PVN of SD rats as well as orexin-A treatment on CaMKII activation in cultured hypothalamic neurons. In vivo sympathetic nerve recordings were employed to test the impact of optogenetic stimulation of CaMKII-expressing PVN neurons on the renal SNA (RSNA) and BP. The results showed that intracerebroventricular injection of orexin-A into the SD rat increases mRNA expression of CaMKII subunits in the PVN. In addition, Orexin-A treatment increases CaMKII expression and its phosphorylation in OX1R-expressing PC12 cells. Furthermore, Orexin-A treatment increases CaMKII activation in cultured hypothalamic neurons from neonatal SD rats. Finally, optogenetic excitation of PVN CaMKII-expressing neurons results in robust increases in RSNA and BP in SD rats. Our results suggest that increased orexin system activity activates CaMKII expression in cardiovascular relevant regions, and this may be relevant to the downstream cardiovascular effects of CaMKII

Constitutive activation of JAK–STAT3 signaling by BRCA1 in human prostate cancer cells

AbstractGerm-line mutations of the breast cancer susceptibility gene 1 (BRCA1) confer a high risk for breast and ovarian cancer in women and prostate cancer in men. The BRCA1 protein contributes to cell proliferation, cell cycle regulation, DNA repair and apoptosis; however, the mechanisms underlying these functions of BRCA1 remain largely unknown. Here, we showed that, in Du-145 human prostate cancer cells, enhanced expression of BRCA1 resulted in constitutive activation of signal transducer and activator transcription factor 3 (STAT3) tyrosine and serine phosphorylation. Moreover, Janus kinase 1 (JAK1) and JAK2, the upstream activators of STAT3, were also activated by BRCA1. Immunoprecipitation assay showed that BRCA1 interacted with JAK1 and JAK2. Blocking STAT3 activation using antisense oligonucleotides significantly inhibited cell proliferation and triggered apoptosis in Du-145 cells with enhanced expression of BRCA1. These findings indicate that BRCA1 interacts with the components of the JAK–STAT signaling cascade and modulates its activation, which may provide a new critical survival signal for the growth of breast, ovarian and prostate cancers in the presence of normal BRCA1

Wet and Dry Atmospheric Depositions of Inorganic Nitrogen during Plant Growing Season in the Coastal Zone of Yellow River Delta

The ecological problems caused by dry and wet deposition of atmospheric nitrogen have been widespread concern in the world. In this study, wet and dry atmospheric depositions were monitored in plant growing season in the coastal zone of the Yellow River Delta (YRD) using automatic sampling equipment. The results showed that SO42- and Na+ were the predominant anion and cation, respectively, in both wet and dry atmospheric depositions. The total atmospheric nitrogen deposition was ~2264.24 mg m−2, in which dry atmospheric nitrogen deposition was about 32.02%. The highest values of dry and wet atmospheric nitrogen deposition appeared in May and August, respectively. In the studied area, NO3-–N was the main nitrogen form in dry deposition, while the predominant nitrogen in wet atmospheric deposition was NH4+–N with ~56.51% of total wet atmospheric nitrogen deposition. The average monthly attribution rate of atmospheric deposition of NO3-–N and NH4+–N was ~31.38% and ~20.50% for the contents of NO3-–N and NH4+–N in 0–10 cm soil layer, respectively, suggested that the atmospheric nitrogen was one of main sources for soil nitrogen in coastal zone of the YRD

Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting

Glioblastoma is the most malignant cancer in the brain and currently incurable. It is urgent to identify effective targets for this lethal disease. Inhibition of such targets should suppress the growth of cancer cells and, ideally also precancerous cells for early prevention, but minimally affect their normal counterparts. Using genetic mouse models with neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) as the cells‐of‐origin/mutation, it is shown that the susceptibility of cells within the development hierarchy of glioma to the knockout of insulin‐like growth factor I receptor (IGF1R) is determined not only by their oncogenic states, but also by their cell identities/states. Knockout of IGF1R selectively disrupts the growth of mutant and transformed, but not normal OPCs, or NSCs. The desirable outcome of IGF1R knockout on cell growth requires the mutant cells to commit to the OPC identity regardless of its development hierarchical status. At the molecular level, oncogenic mutations reprogram the cellular network of OPCs and force them to depend more on IGF1R for their growth. A new‐generation brain‐penetrable, orally available IGF1R inhibitor harnessing tumor OPCs in the brain is also developed. The findings reveal the cellular window of IGF1R targeting and establish IGF1R as an effective target for the prevention and treatment of glioblastoma

Short-term application of diquafosol ophthalmic solution benefits children with dry eye wearing orthokeratology lens

PurposeThis aim of this study was to evaluate the effect of 3% Diquafosol Ophthalmic Solution (DQS) on children with dry eye from wearing overnight orthokeratology (OrthoK) lenses.MethodsMyopic children aged 8–18 years with dry eye syndrome were enrolled in this prospective observational study, and they were grouped according to their OrthoK treatment history for at least 1 year. All participants received DQS 4 times per day for 1 month. The following indicators were measured at baseline 1 month after treatment: the Dry Eye Questionnaire-5 (DEQ-5), non-invasive tear meniscus height (TMH), non-invasive tear film break-up time (first and average, NIBUT-F and NIBUT-A), meibomian gland score (MG score), conjunctival hyperemia redness score (R-scan), and blink pattern analysis.ResultsA total of 104 participants (189 eyes) including 40 OrthoK wearers (72 eyes) and 64 Orthok candidates (117 eyes) completed the study. Of all, after DQS treatment for 1 month, DEQ-5 scores reduced from 5.54 ± 3.25 to 3.85 ± 2.98 (t = −3.36, p = 0.00). TMH increased from 0.20 ± 0.05 mm to 0.21 ± 0.05 mm (t = 2.59, p = 0.01), NIBUT-F and NIBUT-A were prolonged from 6.67 ± 4.71 s to 10.32 ± 6.19 s and from 8.86 ± 5.25 s to 13.30 ± 6.03 s (all p = 0.00), respectively. R-scan decreased from 0.69 ± 0.28 to 0.50 ± 0.25 (t = −9.01, p = 0.00). Upper MG scores decreased from 1.04 ± 0.32 to 0.97 ± 0.36 (t = −2.14, p = 0.03). Lower MG scores, partial blink rate, partial blinks, and total blinks did not change significantly. Both break-up time (BUT) and R-scan improved significantly after DQS treatment for 1 month (all p = 0.00) in OrthoK candidates and OrthoK wearers. Among the OrthoK wearers, TMH and dry eye symptoms increased significantly (all p = 0.00) but did not increase in OrthoK candidates (p > 0.05). There were no adverse events related to DQS.ConclusionDiquafosol Ophthalmic Solution was effective for children wearing overnight orthokeratology in relieving dry eye symptoms and improving ocular surface parameters, which may help improve children's OrthoK wearing tolerance and compliance

Poly (Butylene Succinate)/Silicon Nitride Nanocomposite with Optimized Physicochemical Properties, Biocompatibility, Degradability, and Osteogenesis for Cranial Bone Repair

Congenital disease, tumors, infections, and trauma are the main reasons for cranial bone defects. Herein, poly (butylene succinate) (PB)/silicon nitride (Si3N4) nanocomposites (PSC) with Si3N4 content of 15 w% (PSC15) and 30 w% (PSC30) were fabricated for cranial bone repair. Compared with PB, the compressive strength, hydrophilicity, surface roughness, and protein absorption of nanocomposites were increased with the increase in Si3N4 content (from 15 w% to 30 w%). Furthermore, the cell adhesion, multiplication, and osteoblastic differentiation on PSC were significantly enhanced with the Si3N4 content increasing in vitro. PSC30 exhibited optimized physicochemical properties (compressive strength, surface roughness, hydrophilicity, and protein adsorption) and cytocompatibility. The m-CT and histological results displayed that the new bone formation for SPC30 obviously increased compared with PB, and PSC30 displayed proper degradability (75.3 w% at 12 weeks) and was gradually replaced by new bone tissue in vivo. The addition of Si3N4 into PB not only optimized the surface performances of PSC but also improved the degradability of PSC, which led to the release of Si ions and a weak alkaline environment that significantly promoted cell response and tissue regeneration. In short, the enhancements of cellular responses and bone regeneration of PSC30 were attributed to the synergism of the optimized surface performances and slow release of Si ion, and PSC30 were better than PB. Accordingly, PSC30, with good biocompatibility and degradability, displayed a promising and huge potential for cranial bone construction

The measurement of foreign students'ability of writing in Chinese with a Many-Facets Rasch model

Conference Name:2012 International Symposium on Information Technologies in Medicine and Education, ITME 2012. Conference Address: Hokkaido, Japan. Time:August 3, 2012 - August 5, 2012.IEEE Sapporo Section; Guangzhou University (GZHU); Lanzhou University (LZU); Henan University of Technology (HAUT); Wuhan University of Technology (WHUT)The study employed Many-Facets Rasch Model (MFRM) to validate writing assessment for foreign students learning Chinese. Three raters and 40 foreign university students were involved in the study and four categories of the rating scale were employed to score the compositions of these students. Results show that the rating scale was able to distinguish between different levels of ability of writing in Chinese of the examinees, there were significant differences in their ability of writing in Chinese and that raters used the scale in a consistent and consensus way. 漏 2012 IEEE

Lunar Phases Effect in Chinese Stock Returns

Conference Name:2nd International Conference on Business Intelligence and Financial Engineering. Conference Address: Beijing, PEOPLES R CHINA. Time:JUL 24-26, 2009.This paper investigates the relation between lunar phases and stock market returns of China. The findings indicate that stock returns are lower on the days around a new moon than on the days around a full moon. This pattern of returns is pervasive; we find it for two major Chinese stock indexes over the last 16 years. The author concludes that lunar phases do affect stock returns in china, and the culture is one of the factors which affect investor's sentiment and behavior and then affect stock returns