Controlled delivery of procyanidin through magnesium oxide nanoparticles (MgO NPs) to improve the activity and mineralization of osteoblasts under oxidative stressin vitro.

Excessive reactive oxygen species (ROS) in the microenvironment of osteoporosis (OP) not only accelerate the bone absorption, but also affect the osteogenic and mineralized effect of osteoblasts. Procyanidins (PC) have been reported to have anti-oxidation effects, but low bioavailability. This study aimed to explore the effect of magnesium oxide nanoparticles (MgO-PC NPs)-loaded PC on the osteogenesis and mineralization of osteoblasts that stimulated by H2O2. PC was loaded onto MgO NPs and characterized by transmission electron microscopy, energy dispersive spectroscopy, dynamic light scattering, and Fourier transform infrared spectroscopy. After primary screening by cytotoxicity assay, MgO-PC NPs containing 20 µM of PC were chosen for further studies. In H2O2-stimulated osteoblasts, dichlorodihydrofluorescein diacetate probe, Cell Counting Kit-8, quantitative real-time polymerase chain reaction, alkaline phosphatase staining/activity and Alizarin red staining were used to detect the ROS production, cell viability and osteogenic and mineralized markers of osteoblasts. PC was loaded onto MgO NPs to successfully receive MgO-PC NPs with a diameter of about 144 nm and negative potential. PC can sustain release from MgO-PC NPs for at least 16 d. The controlled release of PC from MgO-PC NPs can effectively eliminate ROS and thereby promoted the cell activity. Most importantly, the osteogenesis and mineralization of osteoblasts under oxidative stress were also significantly reversed by MgO-PC NPS. Thus, these findings indicate that MgO-PC NPs may be developed as a potential therapeutic strategy for OP.

Pathogenesis of Higher Blood Pressure and Worse Renal Function in Salt-Sensitive Hypertension.

BACKGROUND: The underlying pathogenesis of patients with salt-sensitive hypertension expressing higher blood pressure and severer renal damage remains uncertain. METHODS: We recruited 329 subjects, 131 in salt-sensitive (SS) group, 148 in nonsalt-sensitive (NSS) group, and 50 healthy people in normal group and tested their renal function, 24-h ambulatory blood pressure, and growth factor series. RESULTS: The SS group showed worse renal function with lower estimated glomerular filtration rate and higher urinary microalbumin, α-microglobulin, urinary protein Cr ratio, and urinary immunoglobulin. Most indicators in 24-h ambulatory blood pressure of the SS group were significantly enhanced than the NSS group, indicating their higher blood pressure. The significantly elevated growth factors in the SS group were AR, BMP-5, EG-VEGF, GH, HGF, IGFBP-2, IGFBP-3, IGFBP-6, MCSFR, NT-4, PDGF-AA, SCF, SCFR, VEGFR2, VEGFR3, and VEGF-D, compared to other 2 groups or one of them. PI3K-AKT pathway was activated in the SS group. CONCLUSIONS: Differences in growth factors and pathways may account for the manifestations of the SS group. Activated PI3K-AKT pathway with higher IGFBP-3 and GH can lead to renal damage. Higher MCSFR in the SS group indicates that high blood pressure and severe kidney damage may be associated with the activation of the immune system. EG-VEGF, VEGFR2, VEGFR3, and VEGF-D can also explain the elevated blood pressure due to the dilated lymphatic system which drains excess sodium and water back into circulation. The SS group presented higher AR and HGF which may worsen renal function by regulating cell proliferation and tumor formation. However, due to the potential low awareness rate of hypertension at the very beginning, we cannot ensure the exact occurrence order of blood pressure, renal damage, and salt sensitivity. Therefore, further studies which can track data from the onset of hypertension are needed.

Mitochondrial superoxide contributes to oxidative stress exacerbated by DNA damage response in RAD51-depleted ovarian cancer cells.

Ovarian cancer is the most lethal gynecological malignancy. Abnormal homologous recombination repair, high level of reactive oxygen species (ROS) and upregulation of antioxidant genes are characteristic features of ovarian cancer. However, the molecular mechanisms governing the redox homeostasis in ovarian cancer cells remain to be fully elucidated. We here demonstrated a critical role of RAD51, a protein essential for homologous recombination, in the maintenance of redox homeostasis. We found that RAD51 is overexpressed in high grade serous ovarian cancer and is associated with poor prognosis. Depletion or inhibition of RAD51 results in G2/M arrest, increased production of reactive oxygen species and accumulation of oxidative DNA damage. Importantly, antioxidant N-acetylcysteine (NAC) significantly attenuated the induction of DNA damage and the perturbation of proliferation caused by RAD51 depletion. We further demonstrated that RAD51 inhibition or depletion led to elevated production of mitochondrial superoxide and increased accumulation of mitochondria. Moreover, CHK1 activation is required for the G2/M arrest and the generation of mitochondrial stress in response to RAD51 depletion. Together, our results indicate that nuclear DNA damage caused by RAD51 depletion may trigger mitochondria-originated redox dysregulation. Our findings suggest that a vicious cycle of nuclear DNA damage, mitochondrial accumulation and oxidative stress may contribute to the tumor-suppressive effects of RAD51 depletion or inhibition.

Pan-senescence transcriptome analysis identified RRAD as a marker and negative regulator of cellular senescence.

Cellular senescence, an irreversible proliferative arrest, functions in tissue remodeling during development and is implicated in multiple aging-associated diseases. While senescent cells often manifest an array of senescence-associated phenotypes, such as cell cycle arrest, altered heterochromatin architecture, reprogrammed metabolism and senescence-associated secretory phenotype (SASP), the identification of senescence cells has been hindered by lack of specific and universal biomarkers. To systematically identify universal biomarkers of cellular senescence, we integrated multiple transcriptome data sets of senescent cells obtained through different in vitro manipulation modes as well as age-related gene expression data of human tissues. Our analysis showed that RRAD (Ras-related associated with diabetes) expression is up-regulated in all the manipulation modes and increases with age in human skin and adipose tissues. The elevated RRAD expression was then confirmed in senescent human fibroblasts that were induced by Ras, H2O2, ionizing radiation, hydroxyurea, etoposide and replicative passage, respectively. Further functional study suggests that RRAD up-regulation acts as a negative feedback mechanism to counter cellular senescence by reducing the level of reactive oxygen species. Finally, we found both p53 and NF-κB bind to RRAD genomic regions and modulate RRAD transcription. This study established RRAD to be a biomarker as well as a novel negative regulator of cellular senescence.

Equivalent Circuit Model of Low-Frequency Magnetoelectric Effect in Disk-Type Terfenol-D/PZT Laminate Composites Considering a New Interface Coupling Factor.

This paper describes the modeling of magnetoelectric (ME) effects for disk-type Terfenol-D (Tb0.3Dy0.7Fe1.92)/PZT (Pb(Zr,Ti)O3) laminate composite at low frequency by combining the advantages of the static elastic model and the equivalent circuit model, aiming at providing a guidance for the design and fabrication of the sensors based on magnetoelectric laminate composite. Considering that the strains of the magnetostrictive and piezoelectric layers are not equal in actual operating due to the epoxy resin adhesive bonding condition, the magnetostrictive and piezoelectric layers were first modeled through the equation of motion separately, and then coupled together with a new interface coupling factor kc, which physically reflects the strain transfer between the phases. Furthermore, a theoretical expression containing kc for the transverse ME voltage coefficient αv and the optimum thickness ratio noptim to which the maximum ME voltage coefficient corresponds were derived from the modified equivalent circuit of ME laminate, where the interface coupling factor acted as an ideal transformer. To explore the influence of mechanical load on the interface coupling factor kc, two sets of weights, i.e., 100 g and 500 g, were placed on the top of the ME laminates with the same thickness ratio n in the sample fabrication. A total of 22 T-T mode disk-type ME laminate samples with different configurations were fabricated. The interface coupling factors determined from the measured αv and the DC bias magnetic field Hbias were 0.11 for 500 g pre-mechanical load and 0.08 for 100 g pre-mechanical load. Furthermore, the measured optimum thickness ratios were 0.61 for kc = 0.11 and 0.56 for kc = 0.08. Both the theoretical ME voltage coefficient αv and optimum thickness ratio noptim containing kc agreed well with the measured data, verifying the reasonability and correctness for the introduction of kc in the modified equivalent circuit model.

Post-infectious and non post-infectious irritable bowel syndrome: A comparative study.

OBJECTIVE: To compare the post-infectious irritable bowel syndrome (PI-IBS) and none post-infectious irritable bowel syndrome (NPI-IBS) clinically and experimentally. METHODS: From May 2013 to January 2015, eighty-nine patients with irritable bowel syndrome (IBS)were recruited in the internal department of the affiliated hospital of Shandong University of Traditional Chinese Medicine. The clinical data were collected for all the patients, and a blood sample was collected to detect the level of C-reactive protein (CRP) and intestinal fatty acid binding protein (IFABP), an investigation questionnaire of gastrointestinal symptom rating scale (GSRS) and self-rating anxiety scale (SAS) were carried out to evaluate the gastrointestinal function and anxiety status. RESULTS: In the study, forty-eight patients were included in PI-IBS group and 41 in Non-PI-IBS group. There was no significant difference in age, gender and GSRS between the two groups (p>0.05). In PI-IBS group 70.8% patients presented with the primary symptom of diarrhea and 60.4% presented with a SAS scores over 50, but in Non-PI-IBS group, the values were only 19% (p<0.05) and 34.1% (p<0.05). The level of IFABP and CRP were significantly higher in PI-IBS group than those in Non-PI-IBS group (p<0.05). CONCLUSION: The PI-IBS may be different from Non-PI-IBS in mechanism and should be treated using different strategies.

Biophysical regulation of carbon fluxes over an alpine meadow ecosystem in the eastern Tibetan Plateau.

The eddy covariance method was used to measure net ecosystem CO2 exchange (NEE) between atmosphere and an alpine meadow ecosystem in the eastern Tibetan Plateau of China in 2010. Our results show that photosynthesis was reduced under low air temperature (T a), high vapor pressure deficit (VPD), and medium soil water content (SWC) conditions, when compared to that under other T a (i.e., medium and high), VPD (i.e., low and medium), and SWC (i.e., low and high) conditions. The apparent temperature sensitivity of ecosystem respiration (Q 10) declined with progressing phenology during the growing season and decreased with an increase of soil temperature (T s) during the non-growing season. Increased ecosystem respiration (R eco) was measured during spring soil thawing. By the path analysis, T a, T s, and VPD were the main control factors of CO2 exchange at 30-min scale in this alpine meadow. Integrated NEE, gross primary production (GPP), and R eco over the measured year were -156.4, 1164.3, and 1007.9 g C m(-2), respectively. Zoige alpine meadow was a medium carbon sink based on published data for grassland ecosystems.

[Effect of controlled release fertilizer on nitrous oxide emission from paddy field under plastic film mulching cultivation].

A field experiment was conducted to assess the effect of controlled release fertilizer on N2O emission in paddy field under plastic film mulching cultivation (PM) with water-saving irrigation. Results showed that in the rice growing season, cumulative N2O emissions from the plots applied with urea (PM+U) and with controlled release fertilizer (PM+CRF) were (38.2 +/- 4.4) and (21.5 +/- 5.2) mg N x m(-2), respectively. The N2O emission factors were 0.25% and 0.14% in the treatments PM+U and PM+CRF, respectively. The controlled release fertilizer decreased the total N2O emission by 43.6% compared with urea, of which 49.6% was reduced before the drying period. It also reduced the peak of N2O emission by 52.6%. However, it did not affect soil microbial biomass N and soil NH(4+)-N content at any rice growing stage, and grain yield either. No significant correlation was observed between N2O flux and soil Eh or soil temperature at the depth of 5 cm.

[Nitrogen status diagnosis of rice by using a digital camera].

In the present research, a field experiment with different N application rate was conducted to study the possibility of using visible band color analysis methods to monitor the N status of rice canopy. The Correlations of visible spectrum band color intensity between rice canopy image acquired from a digital camera and conventional nitrogen status diagnosis parameters of leaf SPAD chlorophyll meter readings, total N content, upland biomass and N uptake were studied. The results showed that the red color intensity (R), green color intensity (G) and normalized redness intensity (NRI) have significant inverse linear correlations with the conventional N diagnosis parameters of SPAD readings, total N content, upland biomass and total N uptake. The correlation coefficient values (r) were from -0.561 to -0.714 for red band (R), from -0.452 to -0.505 for green band (G), and from -0.541 to 0.817 for normalized redness intensity (NRI). But the normalized greenness intensity (NGI) showed a significant positive correlation with conventional N parameters and the correlation coefficient values (r) were from 0.505 to 0.559. Compared with SPAD readings, the normalized redness intensity (NRI), with a high r value of 0.541-0.780 with conventional N parameters, could better express the N status of rice. The digital image color analysis method showed the potential of being used in rice N status diagnosis in the future.

[Nutrient management strategy of paddy rice-upland crop rotation system].

Paddy rice-upland crop rotation system is a major cropping system in China, and practiced widely along the Yangtze River basin. A unique feature of this system is the annual conversion of soil from aerobic to anaerobic and then back to aerobic condition, which can result in the changes of soil physical, chemical, and biological prosperities among seasons, making a special agroecosystem. The major challenges faced by this system include declining or stagnating productivity, increasing shortage of irrigation water, improper management of nutrients, low efficiency of resource utilization, and environmental pollution. Based on an overview of the characteristics and problems of paddy rice-upland crop rotation system, this paper put forward a strategy of practicing integrated nutrient management to solve the contradictions between nutrient input, crop production and environmental risk. The key points of this strategy included nutrient management from the whole rotation system perspective, integrated use of nutrients from various sources (chemical fertilizers, organic fertilizers, and nutrients from the environment), synchronization of nutrient supply and crop nutrient demand, application of different management technologies based on the characteristics of different nutrient resources, and integration of nutrient management with other cropping system technologies like water saving and high-yielding cultivation, etc.

Particulate air pollution in Lanzhou China.

Concentrations of total suspended particles (TSP) and PM(10) in Lanzhou China have been kept high for the past two decades. Data collected during the intensive observational period from October 1999 to April 2001 show high TSP and PM(10) concentrations. Starting from November, the PM(10) pollution intensifies, and reaches mid to high alert level of air pollution, continues until April next year, and is at low alert level in the summer. In the winter and spring, the TSP concentration is 2-10 times higher than the third-level criterion of air quality (severe pollution). Effects of intrinsic factors (sources of pollution) and remote preconditions (propagation of dust storms) for severe PM(10) and TSP pollution in Lanzhou are analyzed.

Afforestation for reduction of NOX concentration in Lanzhou China.

Lanzhou is one of the major industrial cities in northwest China, the capital of Gansu Province, and located at a northwest-to-southeast oriented valley basin with elevation about 1500-1600-m. Due to topographic and meteorological characteristics, Lanzhou is one of the most polluted cities in China. Meteorological conditions (low winds, stable stratification especially inversion), pollutant sources and sinks affect the air quality. Lanzhou government carried out afforestation and pollutant-source reduction (closing several heavy industrial factories) to improve the air quality for the past two decades. In this study, effect of afforestation on reducing the NO(X) concentration is investigated numerically using RAMS-HYPACT model.

Further evidence for BRCA1 communication with the inactive X chromosome.

BRCA1, a breast and ovarian cancer-suppressor gene, exerts tumor-suppressing functions that appear to be associated, at least in part, with its DNA repair, checkpoint, and mitotic regulatory activities. Earlier work from our laboratory also suggested an ability of BRCA1 to communicate with the inactive X chromosome (Xi) in female somatic cells (Ganesan et al., 2002). Xiao et al. (2007) (this issue of Cell) have challenged this conclusion. Here we discuss recently published data from our laboratory and others and present new results that, together, provide further support for a role of BRCA1 in the regulation of XIST concentration on Xi in somatic cells.

[The electrical conductivity of triggered lightning channel].

Spectra of return strokes for artificial triggered lightning were obtained by optical multi-channel analyzer (OMA) in Shandong region. Compared with previous spectra of natural lightning, additional lines of ArI 602.5 nm and ArII 666.5 nm were observed. Under the model of local thermodynamic equilibrium, electronic temperatures of the lightning channel plasma were obtained according to the relative line intensities. Meanwhile, with semi-empirical method the electron density was obtained by Halpha line Stark broadening. In combination with plasma theory, electrical conductivity of the lightning channel has been calculated for the first time, and the characteristic of conductivity for lightning channel was also discussed. The relation between the electrical conductivity of channel and the return stroke current was analyzed, providing reference data for further work on computing return stroke current. Results show that the lightning channel is a good conductor, and electrons are the main carrier of channel current. The brightness of artificial triggered lightning channel is usually higher than that of natural lightning, and its current is smaller than that of the natural lightning.

[The spectral properties of an intense lightning return stroke].

The spectrum in the range of 400-600 nm from the first return stroke of an intense cloud-to-ground lightning flash was obtained by a slit-free spectrograph. Applying the atomic structure theory to the research work on lightning spectra, the wavelengths, oscillator strengths and excitation energies of upper levels were calculated for the transitions of related lightning spectrum. Multi-configuration Dirac-Fock method was employed in the calculation. From the results, re-identifications were carried out for the lines of 419.0 and 425.3 nm. It was found by spectral analysis combined with corresponding electrical information finds that the spectrum characteristic is closely related to the intensity of lightning discharge, as during an intense lightning return stroke the lines of O II with high excitation energies are enhanced.

Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed.

The pathogenic lymphocryptovirus Epstein-Barr virus (EBV) is shown to express at least 17 distinct microRNAs (miRNAs) in latently infected cells. These are arranged in two clusters: 14 miRNAs are located in the introns of the viral BART gene while three are located adjacent to BHRF1. The BART miRNAs are expressed at high levels in latently infected epithelial cells and at lower, albeit detectable, levels in B cells. In contrast to the tissue-specific expression pattern of the BART miRNAs, the BHRF1 miRNAs are found at high levels in B cells undergoing stage III latency but are essentially undetectable in B cells or epithelial cells undergoing stage I or II latency. Induction of lytic EBV replication was found to enhance the expression of many, but not all, of these viral miRNAs. Rhesus lymphocryptovirus, which is separated from EBV by > or =13 million years of evolution, expresses at least 16 distinct miRNAs, seven of which are closely related to EBV miRNAs. Thus, lymphocryptovirus miRNAs are under positive selection and are likely to play important roles in the viral life cycle. Moreover, the differential regulation of EBV miRNA expression implies distinct roles during infection of different human tissues.

Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells.

MicroRNAs (miRNAs) are an endogenously encoded class of small RNAs that have been proposed to function as key posttranscriptional regulators of gene expression in a range of eukaryotic species, including humans. The small size of miRNA precursors makes them potentially ideal for use by viruses as inhibitors of host cell defense pathways. Here, we demonstrate that the pathogenic human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) encodes an array of 11 distinct miRNAs, all of which are expressed at readily detectable levels in latently KSHV infected cells. Individual KSHV miRNAs were expressed at up to 2,200 copies per cell. The KSHV miRNAs are expressed from what appears to be a single genetic locus that largely coincides with an approximately 4-kb noncoding sequence located between the KSHV v-cyclin and K12/Kaposin genes, both of which are also expressed in latently infected cells. Computer analysis of potential mRNA targets for these viral miRNAs identified a number of interesting candidate genes, including several mRNAs previously shown to be down-regulated in KSHV-infected cells. We hypothesize that these viral miRNAs play a critical role in the establishment and/or maintenance of KSHV latent infection in vivo and, hence, in KSHV-induced oncogenesis.

Adenovirus VA1 noncoding RNA can inhibit small interfering RNA and MicroRNA biogenesis.

Although inhibition of RNA interference (RNAi) by plant virus proteins has been shown to enhance viral replication and pathogenesis in plants, no viral gene product has as yet been shown to inhibit RNAi in vertebrate cells. Here, we present evidence demonstrating that the highly structured approximately 160-nucleotide adenoviral VA1 noncoding RNA can inhibit RNAi at physiological levels of expression. VA1, which is expressed at very high levels in adenovirus-infected cells, potently inhibited RNAi induced by short hairpin RNAs (shRNAs) or human microRNA precursors but did not affect RNAi induced by artificial short interfering RNA duplexes. Inhibition appeared to be due both to inhibition of nuclear export of shRNA or premicro-RNA precursors, competition for the Exportin 5 nuclear export factor, and inhibition of Dicer function by direct binding of Dicer. Together, these data argue that adenovirus infection can result in inhibition of RNAi and identify VA1 RNA as the first viral gene product able to inhibit RNAi in human cells.

Nonsense mediated decay induced by tethered human UPF3B is restricted to the cytoplasm.

The subcellular localization of the nonsense mediated decay (NMD) of mRNA transcripts bearing premature termination codons has been controversial. Recently, it has been demonstrated that RNA tethering of key mediators of NMD, including human UPF3B, accurately recreates NMD. Here, we have used tethered UPF3B, combined with regulation of nuclear mRNA export using the retroviral Rev/RRE system, to examine where UPF3B-mediated mRNA degradation occurs. Our data clearly demonstrate that nuclear mRNA export is required for UPF3B-mediated degradation and moreover show that this degradation is exclusively cytoplasmic, despite the fact that the UPF3B fusion protein used is a nucleocytoplasmic shuttle protein localized predominantly to the nucleus. Moreover, exclusively cytoplasmic NMD occurred whether the target mRNA was exported via the retroviral Rev/RRE pathway or via the Tap: Nxt pathway used by most cellular mRNAs. These data may suggest that truly nuclear NMD, if it occurs, is at least in part mechanistically distinct from cytoplasmic NMD.