Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease that is caused by a novel bunyavirus, referred to as SFTS virus. During January 2011 to December 2011 we conducted a case-control study in Henan, Hubei and Shandong Provinces of China to determine the risk factors for SFTS.
Multiple surgical techniques in minimally invasive total knee arthroplasty (TKA) are associated with clinical differences. However, whether patellar eversion impairs clinical outcomes remains controversial. We conducted a systematic review of randomized controlled trials (RCTs) to provide current understanding on this topic.
The measurement of the flow rate of various liquids and gases is critical in industrial automation. Rotary positive displacement meters (rotary PD meters) are highly accurate flowmeters that are widely employed in engineering applications, especially in custody transfer operations and hydraulic control systems. This paper presents a high pressure rotary PD meter containing a pair of internal cycloid rotors. It has the advantages of concise structure, low pressure loss, high accuracy and low noise. The curve of the internal rotor is designed as an equidistant curtate epicycloid curve with the external rotor curve as its conjugate. The calculation method used to determine the displacement of the cycloid rotor flowmeter is discussed. A prototype was fabricated, and experiments were performed to confirm measurements over a flow range of 1-100 L/min with relative errors of less than ±0.5%. The pressure loss through the flowmeter was about 3 bar at a flow rate of 100 L/min.
The majority of human cases of novel avian influenza A(H7N9), which emerged in China in spring 2013, include reported exposure to poultry. However, specific host and exposure risk factors for disease are unknown, yet critical to design prevention measures.
A novel linear ion trap mass analyzer built with four triangular electrodes, the triangular-electrode linear ion trap (TeLIT), has been built and its performance has been characterized. The TeLIT has all the properties of a conventional LIT mass analyzer, performing ion trapping, mass analysis, and tandem mass spectrometry functions. The TeLIT was constructed with four identical triangular cross-section shaped electrodes and two planar electrodes. Unlike commercial LITs, which have very well-defined hyperbolic shaped electrodes, the TeLIT electrodes have a much simpler geometric structure and larger mechanical tolerances. The electric field distribution inside the IT region was simulated and there are more quadrupole field components and less higher order fields compared with those in other simplified ITs, such as cylindrical ion trap and rectilinear ion trap; hence, the instrument would potentially offer a relatively high mass resolution. In routine measurement, mass analysis with a resolving power of over 1500 at m/z = 609 Th was obtained. The TeLIT was shown to perform basic mass spectrometer functions such as mass-selected isolation, mass-selected ejection and collision-induced dissociation (CID) of ions comparable to other available LITs. Moreover, given the small size of the TeLIT and its simple structure and good analytical performance, further miniaturization and use as a portable mass spectrometer are envisaged.
The optimal surgical technique for multilevel cervical degenerative disc diseases (DDD) remains controversial. Hybrid surgery (HS) incorporating anterior cervical discectomy and fusion (ACDF) and cervical disc replacement (CDR) is increasingly performed for cervical DDD. This study aims to evaluate the biomechanical and clinical evidence available for HS and to provide a systematic review of current understanding of HS.
The pivotal challenge associated with miniature mass analyzers is their proper design and construction without sacrificing performance. In order to analyze and improve the performance of a miniature linear ion trap with odd and even multipole fields, we designed a novel asymmetrical arc-shaped electrode ion trap (AAEIT), and tested the properties of AAEITs with different dimensions.
Japanese encephalitis (JE) is the most common cause of viral encephalitis and an important public health concern in the Asia-Pacific region, particularly in China where 50% of global cases are notified. To explore the association between environmental factors and human JE cases and identify the high risk areas for JE transmission in China, we used annual notified data on JE cases at the center of administrative township and environmental variables with a pixel resolution of 1km×1km from 2005 to 2011 to construct models using ecological niche modeling (ENM) approaches based on maximum entropy. These models were then validated by overlaying reported human JE case localities from 2006 to 2012 onto each prediction map. ENMs had good discriminatory ability with the area under the curve (AUC) of the receiver operating curve (ROC) of 0.82-0.91, and low extrinsic omission rate of 5.44-7.42%. Resulting maps showed JE being presented extensively throughout southwestern and central China, with local spatial variations in probability influenced by minimum temperatures, human population density, mean temperatures, and elevation, with contribution of 17.94%-38.37%, 15.47%-21.82%, 3.86%-21.22%, and 12.05%-16.02%, respectively. Approximately 60% of JE cases occurred in predicted high risk areas, which covered less than 6% of areas in mainland China. Our findings will help inform optimal geographical allocation of the limited resources available for JE prevention and control in China, find hidden high-risk areas, and increase the effectiveness of public health interventions against JE transmission.
Collision-induced dissociation (CID) of ions by resonance activation in a quadrupole ion trap is usually accomplished by resonance exciting the ions to higher kinetic energy, whereby the high kinetic energy ions collide with a bath gas, such as helium or argon, inside the trap and dissociate to fragments. A new ion activation method using a well-defined rectangular wave dipolar potential formed by dividing down the trapping rectangular waveform is developed and examined herein. The mass-selected parent ions are resonance excited to high kinetic energies by simply changing the frequency of the rectangular wave dipolar potential and dissociation proceeds. A relationship between the ion mass and the activation waveform frequency is also identified and described. This highly efficient (CID) procedure can be realized by simply changing the waveform frequency of the dipolar potential, which could certainly simplify tandem mass spectrometry analysis methods.
A mesh-electrode linear ion trap (ME-LIT) mass analyzer was developed and its performance was primarily characterized. In conventional linear ion trap mass analyzers, the trapped ions are mass-selected and then ejected in a radial direction by a slot on a trap electrode. The presence of slots can strongly affect the electric field distribution in the ion trapping region and distort the mass analysis performance. To compensate for detrimental electric field effects, the slot is usually designed and fabricated to be as small as possible, and also has very high mechanical accuracy and symmetry. A ME-LIT with several mesh electrodes was built to compensate for the effects caused by slots. Each mesh electrode was fabricated from a plate electrode with a relatively large slot and the slot was covered with a conductive mesh. Our preliminary experimental results show that the ME-LIT could considerably diminish the detrimental electric field effects caused by slots, and increase the mass resolving power and ion detection efficiency. Even with 4-mm-wide slots, a mass resolution in excess of 600 was obtained using the ME-LIT. Mass resolution could be remarkably improved using mesh electrodes in ion traps with asymmetric electrodes. The stability diagram of the ME-LIT was mapped, and highly efficient tandem mass spectrometry was demonstrated. The ME-LIT was qualified as a LIT mass analyzer. The ME-LIT can improve the mass resolution and decrease the requirements of mechanical accuracy and symmetry of slots, so it shows potential for a wide range of practical uses.
A recombinant plasmid expressing the VP6 inner capsid coding gene of grass carp reovirus (GCRV) was constructed and expressed in a Ctenopharyngodon idellus kidney (CIK) cell line and grass carps. The VP6 gene was amplified by RT-PCR, cloned into a pEGFP-N1 eukaryotic expression vector and transfected into CIK cells. Results from enhanced green fluorescent protein (EGFP) experiments and flow cytometry showed highest protein expression at 48 h. The immunoreactivity of fusion protein was confirmed using an indirect immunofluorescent assay. The specific binding between the fusion protein and polyclonal mouse GCRV VP6-specific antiserum indicated that the fusion protein was translated in vitro and had good immunogenicity. An antiviral activity assay showed that the virus titer was 100-fold lower in the GCRV VP6 expressed cells than in the pEGFP-N1 transfected cells. The expression levels of three immune genes in the head kidney of grass carps injected with the recombinant plasmid were used. Mx, TLR3 and IgM mRNA expression increased sharply at the 1st and 15th days post-injection (dpi). Specific antibodies were detected 30 days after vaccination. Neutralizing titers of the antibodies in vaccinated fish detected ranged from 160 to 320. Intramuscular injection of grass carps with 1 ?g of pEGFP-N1-VP6 was found to provide strong protection against GCRV. These results suggested that the VP6 gene was a good candidate for the design of GCRV-DNA vaccines and to investigate the use of cytokines as co-stimulatory molecules.
It is widely recognized that global warming promotes soil organic carbon (SOC) decomposition, and soils thus emit more CO2 into the atmosphere because of the warming; however, the response of SOC decomposition to this warming in different soil textures is unclear. This lack of knowledge limits our projection of SOC turnover and CO2 emission from soils after future warming. To investigate the CO2 emission from soils with different textures, we conducted a 107-day incubation experiment. The soils were sampled from temperate forest and grassland in northern China. The incubation was conducted over three short-term cycles of changing temperature from 5°C to 30°C, with an interval of 5°C. Our results indicated that CO2 emissions from sand (>50 µm), silt (2-50 µm), and clay (<2 µm) particles increased exponentially with increasing temperature. The sand fractions emitted more CO2 (CO2-C per unit fraction-C) than the silt and clay fractions in both forest and grassland soils. The temperature sensitivity of the CO2 emission from soil particles, which is expressed as Q10, decreased in the order clay>silt>sand. Our study also found that nitrogen availability in the soil facilitated the temperature dependence of SOC decomposition. A further analysis of the incubation data indicated a power-law decrease of Q10 with increasing temperature. Our results suggested that the decomposition of organic carbon in fine-textured soils that are rich in clay or silt could be more sensitive to warming than those in coarse sandy soils and that SOC might be more vulnerable in boreal and temperate regions than in subtropical and tropical regions under future warming.
This study aimed to investigate the inhibitory mechanism of root growth and to compare antioxidative responses in two wheat cultivars, drought-tolerant Ningchun and drought-sensitive Xihan, exposed to different NaCl concentrations. Ningchun exhibited lower germination rate, seedling growth, and lipid peroxidation than Xihan when exposed to salinity. The loss of cell viability was correlated with the inhibition of root growth induced by NaCl stress. Moreover, treatments with H2O2 scavenger dimethylthiourea and catalase (CAT) partly blocked salinity-induced negative effects on root growth and cell viability. Besides, the enhancement of superoxide radical and H2O2 levels, and the stimulation of CAT and diamine oxidase (DAO) as well as the inhibition of glutathione reductase (GR) were observed in two wheat roots treated with salinity. However, hydroxyl radical content increased only in Xihan roots under NaCl treatment, and the changes of soluble peroxidase (POD), ascorbate peroxidase (APX), superoxide dismutase (SOD), and cell-wall-bound POD activities were different in drought-tolerant Ningchun and drought-sensitive Xihan exposed to different NaCl concentrations. In conclusion, salinity might induce the loss of cell viability via a pathway associated with extracellular H2O2 generation, which was the primary reason leading to the inhibition of root growth in two wheat cultivars. Here, it was also suggested that increased H2O2 accumulation in the roots of drought-tolerant Ningchun might be due to decreased POD and GR activities as well as enhanced cell-wall-bound POD and DAO ones, while the inhibition of APX and GR as well as the stimulation of SOD and DAO was responsible for the elevation of H2O2 level in drought-sensitive Xihan roots.
The surface layer of the sclerotia of Poria cocos, named Fu-Ling-Pi, is used as a diuretic in traditional Chinese medicine to treat edema and urinary dysfunction. Recent studies have showed that the triterpenes (lanostane and 3,4-secolanostane skeletons) and polysaccharides (beta-pachyman) are the main components of Fu-Ling-Pi and they exhibited various biological activities, such as anti-tumor, antibacterial and antioxidant, etc. This review was focused on the chemistry, pharmacology, and clinical uses of this drug and it may provide scientific foundation for further development and utilization of Fulingpi.
An ion trap (IT) mass analyzer can be simply built with low cost material-the printed circuit board (PCB). A printed circuit board ion trap (PCBIT) can perform ion trapping, mass analysis, and tandem mass spectrometry as a conventional ion trap mass analyzer. In a PCBIT, each PCB electrode was fabricated to specially designed patterns with several separate electric strips. The strips electrodes were insulated from each other and applied with different voltages during the experiment. Therefore, the electric field distribution inside the ion trap region may be adjusted and optimized by simply adjusting the voltage on each strip. The performance of the PCBIT can also be optimized since the property of an ion trap is strongly dependent on the field distribution. The fabrication, operation, and performance of the PCBIT are described and characterized in this paper. A prototype PCBIT was built with two pairs of 64 mm × 12 mm PCB rectangular plates and one pair of 10 mm × 10 mm stainless steel square plates. A mass analysis with a resolving power of over 1500 and a mass range of around 3000 Th was observed. The mass-selected isolation and collision-induced dissociation (CID) of ions were also tested using the homemade PCBIT system. The adjustable electric field distribution, simple structure, and low cost of PCBIT make it certainly suitable for the further miniaturization of the portable mass spectrometer.
The aim of the study is to examine the spatiotemporal pattern of Japanese Encephalitis (JE) in mainland China during 2002-2010. Specific objectives of the study were to quantify the temporal variation in incidence of JE cases, to determine if clustering of JE cases exists, to detect high risk spatiotemporal clusters of JE cases and to provide evidence-based preventive suggestions to relevant stakeholders.
The main bitter compounds (nomilin, limonin and naringin) in the fruit tissues of Guoqing No.1 Satsuma mandarin (Citrus unshiu Marc.) were determined throughout the fruit development of 3 consecutive growing seasons. Although fluctuating largely at the corresponding developing stages of the 3 years, the contents of these compounds in fruit tissues mostly displayed a declining trend, which implied that the rhythm of the metabolism of these bitter compounds was not consistent among years and was largely growing season dependent. Regarding their distribution, fruit flavedo might be a weak sink that contained the lowest level of naringin, while the segment membrane accumulated large amount of limonin and nomilin, which indicated a possible tissue bias pattern for biosynthesis or accumulation of those compounds. Partial correlation coefficient analysis revealed a synergistic accumulation of naringin and the two limonoid aglycones in fruit tissues during fruit development, indicating an integrated metabolism of flavonoids and limonoids.
Background The first identified cases of avian influenza A (H7N9) virus infection in humans occurred in China during February and March 2013. We analyzed data obtained from field investigations to characterize the epidemiologic characteristics of H7N9 cases in China as of April 17, 2013. Methods Field investigations were conducted for each confirmed case of H7N9 virus infection. A patient was considered to have a confirmed case if the presence of the H7N9 virus was verified by means of real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR), viral isolation, or serologic testing. Information on demographic characteristics, exposure history, and illness timelines was obtained from patients with confirmed cases. Close contacts were monitored for 7 days for symptoms of illness. Throat swabs were obtained from contacts in whom symptoms developed and were tested for the presence of the H7N9 virus testing by means of real-time RT-PCR. Results Among 82 persons with confirmed H7N9 virus infection, the median age was 63 years (range, 2 to 89), 73% were male, and 84% were urban residents. Confirmed cases occurred in six areas of China. Of 77 persons with available data, 4 were poultry workers, and 77% had a history of exposure to live animals, including chickens (76%). A total of 17 persons (21%) died after a median duration of illness of 11 days, 60 remain critically ill, and 4 with clinically mild cases were discharged from the hospital; 1 pediatric patient was not admitted to the hospital. In two family clusters, human-to-human transmission of H7N9 virus could not be ruled out. A total of 1251 of the 1689 close contacts of case patients completed the monitoring period; respiratory symptoms developed in 19 of them (1.5%), all of whom tested negative for the H7N9 virus. Conclusions Most persons with confirmed H7N9 virus infection were critically ill and epidemiologically unrelated. Laboratory-confirmed human-to-human H7N9 virus transmission was not documented among close contacts, but such transmission could not be ruled out in two families.
Transmissible gastroenteritis virus (TGEV) is a porcine coronavirus that can cause piglet diarrhea with high mortality rates. TGEV membrane (M) protein not only plays a vital role in the process of virus assembly and budding, but also induces the production of interferon-? during infection. In this study, a monoclonal antibody (MAb) designated 7G7, against the TGEV M protein was generated by inoculating BALB/c mice with TGEV followed by hybridoma technique. Immunofluorescence assays indicated that MAb 7G7 was capable of detecting cell infection by TGEV. Virus-based ELISA demonstrated that MAb 7G7 can be used as a highly specific diagnostic reagent for TGEV.
Prostate cancer (PCa) stem/progenitor cells are known to have higher chemoresistance than non-stem/progenitor cells, but the underlying molecular mechanism remains unclear. We found the expression of testicular nuclear receptor 4 (TR4) is significantly higher in PCa CD133(+) stem/progenitor cells compared with CD133(-) non-stem/progenitor cells. Knockdown of TR4 levels in the established PCa stem/progenitor cells and the CD133(+) population of the C4-2 PCa cell line with lentiviral TR4 siRNA led to increased drug sensitivity to the two commonly used chemotherapeutic drugs, docetaxel and etoposide, judging from significantly reduced IC50 values and increased apoptosis in the TR4 knockdown cells. Mechanism dissection studies found that suppression of TR4 in these stem/progenitor cells led to down-regulation of Oct4 expression, which, in turn, down-regulated the IL-1 receptor antagonist (IL1Ra) expression. Neutralization experiments via adding these molecules into the TR4 knockdown PCa stem/progenitor cells reversed the chemoresistance, suggesting that the TR4-Oct4-IL1Ra axis may play a critical role in the development of chemoresistance in the PCa stem/progenitor cells. Together, these studies suggest that targeting TR4 may alter chemoresistance of PCa stem/progenitor cells, and this finding provides the possibility of targeting TR4 as a new and better approach to overcome the chemoresistance problem in PCa therapeutics.
Monosodium L-glutamate (MSG) is a food flavour enhancer and its potential harmfulness to the heart remains controversial. We investigated whether MSG could induce cardiac arrhythmias and apoptosis via the ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor.
It has been shown that bupivacaine, the most commonly used local anesthetic to relieve or control pain in interventional spine procedures, is cytotoxic to intervertebral disc (IVD) cells in vitro. However, some other common local anesthetics, such as ropivacaine and lidocaine, are also frequently used in the treatment of spine-related pain, and the potential effects of these agents remain unclear.
Degeneration of intervertebral disc (IVD) is mainly a chronic process of excessive destruction of the extracellular matrix (ECM), and also is thought to be the primary cause of low back pain. Presently, however, the underlying mechanism of IVD degeneration is still not elucidated. Cellular loss from cell death has been believed to contribute to the degradation of ECM and plays an important role in the process of IVD degeneration, but the mechanisms of cell death in degenerated IVD remain unclear. Apoptosis, a very important type of IVD cell death, has been considered to play a crucial role in the process of degeneration. Autophagy, a non-apoptosis death type of programmed cell death, has been considered extensively involved in many pathological and physiological processes, including the degenerative diseases. Thus, the research on cell death in IVD degeneration has become a new focus recently. In this review, by analyzing the available literature pertaining to cell death in IVD and discussing the inducing factors of IVD degeneration, NP cells and ECM in IVD degeneration, apoptotic signal transduction pathways involved in IVD cell death, the relationship of cell death with IVD degeneration and potential therapeutic strategy for IVD degeneration by regulating cell death, we conclude that different stimuli induce cell death in IVD via various signal transduction pathways, and that cell death may play a key role in the degenerative process of IVD. Regulation of cell death could be a potential and attractive therapeutic strategy for IVD degeneration.
Nitric oxide (NO) is a stress factor or a signal molecule involved in various plant physiological and developmental processes. In the present study, the generation of reactive oxygen species and the metabolism of proline due to different sodium nitroprusside (SNP, an NO donor) concentrations were investigated in callus from halophyte Nitraria tangutorum Bobr. Treatment with SNP led to significant increases of hydrogen peroxide (H2O2) content and cell viability but notable reductions in hydrogen radical level and lipid peroxidation degree, and superoxide onion (O2 (-)) content also enhanced in 100 ?M SNP-treated calli. Using a chemical inhibitor for plasma membrane (PM) NADPH oxidase diphenylene iodonium (DPI), we found low O2 (-) generation in untreated and 25 ?M SNP-treated calli, whereas in those treated with 100 ?M SNP O2 (-) level exhibited a very little alteration, comparable to the absence of DPI. These suggest a high activity of PM NADPH oxidase in untreated calli. H2O2 scavenging enzymes (catalase, peroxidase [POD] and ascorbate peroxidase) and H2O2 forming enzymes (superoxide dismutase [SOD], cell wall-POD and diamine oxidase [DAO]) stimulated significantly in calli treated with different SNP concentrations while glutathione reductase activity decreased. In addition, a reduction in proline content was observed in SNP-treated calli. Moreover, different SNP concentrations stimulated proline dehydrogenase (PDH) and ornithine ?-aminotransferase but inhibited r-glutamyl kinase (GK). In conclusion, our results suggest that the increasing H2O2 generation was associated with the stimulation of SOD, cell wall-POD and DAO, and that the reduction of proline content might be the consequence of increased PDH activity and decreased GK activity in N. tangutorum Bobr. calli under SNP treatment.
A novel ion trap array (ITA) mass analyzer with six ion trapping and analyzing channels was investigated. It is capable of analyzing multiple samples simultaneously. The ITA was built with several planar electrodes made of stainless steel and 12 identical parallel zirconia ceramic substrates plated with conductive metal layers. Each two of the opposing ceramic electrode plates formed a boundary of an ion trap channel and six identical ion trapping and analyzing channels were placed in parallel without physical electrode between any two adjacent channels. The electric field distribution inside each channel was studied with simulation. The new design took the advantage of high precision machining attributable to the rigidity of ceramic, and the convenience of surface patterning technique. The ITA system was tested by using a two-channel electrospray ionization source, a multichannel simultaneous quadruple ion guide, and two detectors. The simultaneous analysis of two different samples with two adjacent ITA channels was achieved and independent mass spectra were obtained. For each channel, the mass resolution was tested. Additional ion trap functions such as mass-selected ion isolation and collision-induced dissociation (CID) were also tested. The results show that one ITA is well suited for multiple simultaneous mass analyses.
The context and purpose of the study included 1) bacterial expression of viral protein 6 (VP6) of porcine rotavirus (PRV) and generation of rabbit polyclonal antiserum to the VP6 protein; 3) establishment of a discrimination ELISA to distinguish PRV from a panel of other porcine viruses.
Testicular nuclear receptor 4 (TR4), also known as NR2C2 (nuclear receptor subfamily 2, group C, member 2), is a transcriptional factor and a member of the nuclear receptor family. TR4 was initially cloned from human and rat hypothalamus, prostate, and testes libraries. For almost two decades, its specific tissue distribution, genomic organization, and chromosomal assignment have been well investigated in humans and animals. However, it has been very difficult to study TR4s physiological functions due to a lack of specific ligands. Gene knock-out animal techniques provide an alternative approach for defining the biological functions of TR4. In vivo studies of TR4 gene knockout mice (TR4(-/-)) found that they display severe spinal curvature, subfertility, premature aging, and prostate prostatic intraepithelial neoplasia (PIN) development. Upstream modulators, downstream target gene regulation, feedback mechanisms, and differential modulation mediated by the recruitment of other nuclear receptors and coregulators have been identified in studies using the TR4(-/-) phenotype. With the establishment of a tissue-specific TR4(-/-) mouse model, research on TR4 will be more convenient in the future.
Previously, we demonstrated that reproductive senescence in female triple transgenic Alzheimers (3×TgAD) mice was paralleled by a shift towards a ketogenic profile with a concomitant decline in mitochondrial activity in brain, suggesting a potential association between ovarian hormone loss and alteration in the bioenergetic profile of the brain. In the present study, we investigated the impact of ovariectomy and 17?-estradiol replacement on brain energy substrate availability and metabolism in a mouse model of familial Alzheimers (3×TgAD). Results of these analyses indicated that ovarian hormones deprivation by ovariectomy (OVX) induced a significant decrease in brain glucose uptake indicated by decline in 2-[(18)F]fluoro-2-deoxy-D-glucose uptake measured by microPET-imaging. Mechanistically, OVX induced a significant decline in blood-brain-barrier specific glucose transporter expression, hexokinase expression and activity. The decline in glucose availability was accompanied by a significant rise in glial LDH5 expression and LDH5/LDH1 ratio indicative of lactate generation and utilization. In parallel, a significant rise in ketone body concentration in serum occurred which was coupled to an increase in neuronal MCT2 expression and 3-oxoacid-CoA transferase (SCOT) required for conversion of ketone bodies to acetyl-CoA. In addition, OVX-induced decline in glucose metabolism was paralleled by a significant increase in A? oligomer levels. 17?-estradiol preserved brain glucose-driven metabolic capacity and partially prevented the OVX-induced shift in bioenergetic substrate as evidenced by glucose uptake, glucose transporter expression and gene expression associated with aerobic glycolysis. 17?-estradiol also partially prevented the OVX-induced increase in A? oligomer levels. Collectively, these data indicate that ovarian hormone loss in a preclinical model of Alzheimers was paralleled by a shift towards the metabolic pathway required for metabolism of alternative fuels in brain with a concomitant decline in brain glucose transport and metabolism. These findings also indicate that estrogen plays a critical role in sustaining brain bioenergetic capacity through preservation of glucose metabolism.
Chinese tree shrews (Tupaia belangeri chinensis) possess many features valuable in animals used as experimental models in biomedical research. Currently, there are numerous attempts to employ tree shrews as models for a variety of human disorders: depression, myopia, hepatitis B and C virus infections, and hepatocellular carcinoma, to name a few. Here we present a publicly available annotated genome sequence for the Chinese tree shrew. Phylogenomic analysis of the tree shrew and other mammalians highly support its close affinity to primates. By characterizing key factors and signalling pathways in nervous and immune systems, we demonstrate that tree shrews possess both shared common and unique features, and provide a genetic basis for the use of this animal as a potential model for biomedical research.
A digital ion trap (DIT) and rectilinear ion trap (RIT) have been proven to be very useful technology in the past years. In this work, the digital ion trap technology was combined with the ceramic-based rectilinear ion trap (cRIT) system. The rectangular waveform was used for ion trapping. A dipolar excitation waveform which was formed by dividing down the trapping rectangular waveform was used for the ion ejection. We found that the high efficient collision-induced dissociation (CID) procedure could be obtained by simply manipulating the duty cycle of the dipole excitation waveform, and it could significantly simplify the tandem mass spectrometry analysis method and procedure with an ion trap, since the dipolar direct current (dc) voltage could be easily produced and applied to one of the pair of electrodes, which was fully controlled by the computer software and does not need any hardware modification.
We previously demonstrated that mitochondrial bioenergetic deficits in the female brain accompanied reproductive senescence and was accompanied by a shift from an aerobic glycolytic to a ketogenic phenotype. Herein, we investigated the relationship between systems of fuel supply, transport and mitochondrial metabolic enzyme expression/activity during aging (3-15 months) in the hippocampus of nontransgenic (nonTg) background and 3xTgAD female mice. Results indicate that during female brain aging, both nonTg and 3xTgAD brains undergo significant decline in glucose transport, as detected by FDG-microPET, between 6-9 months of age just prior to the transition into reproductive senescence. The deficit in brain metabolism was sustained thereafter. Decline in glucose transport coincided with significant decline in neuronal glucose transporter expression and hexokinase activity with a concomitant rise in phosphorylated/inactivated pyruvate dehydrogenase. Lactate utilization declined in parallel to the decline in glucose transport suggesting lactate did not serve as an alternative fuel. An adaptive response in the nonTg hippocampus was a shift to transport and utilization of ketone bodies as an alternative fuel. In the 3xTgAD brain, utilization of ketone bodies as an alternative fuel was evident at the earliest age investigated and declined thereafter. The 3xTgAD adaptive response was to substantially increase monocarboxylate transporters in neurons while decreasing their expression at the BBB and in astrocytes. Collectively, these data indicate that the earliest change in the metabolic system of the aging female brain is the decline in neuronal glucose transport and metabolism followed by decline in mitochondrial function. The adaptive shift to the ketogenic system as an alternative fuel coincided with decline in mitochondrial function. Translationally, these data provide insights into the earliest events in bioenergetic aging of the female brain and provide potential targets for preventing shifts to less efficient bioenergetic fuels and transition to the ketogenic phenotype of the Alzheimers brain.
Studies designed to evaluate the association of hyperglycemia and adverse events in pediatric patients receiving open cardiac surgery have yielded inconsistent results. The aim of this retrospective, observational study was to evaluate the effects of peri-operative glucose levels on adverse events in infants receiving open-heart surgery with CPB.
The non-covalent complexes of alpha- and beta-cyclodextrins (alpha-, beta-CDs) with two aryl alkanol piperazine derivatives (Pipe I and Pipe II) have been studied by electrospray ionization mass spectrometry (ESI-MS) and fluorescence spectroscopy. The ESI-MS experimental results demonstrated that Pipe I can conjugate to beta-CD and form 1:1 or 1:2 stoichiometric non-covalent complexes, and Pipe II can only form 1:1 complexes with alpha- or beta-CD. Fluorescence spectra indicated that the fluorescence intensities of Pipe I and Pipe II can be enhanced by increasing the content of beta-CD. The mass spectrometric titration experiments showed that the dissociation constants K(d1) were 5.77 and 9.52 x 10(-4) mol L(-1) for the complexes of alpha-CD with Pipe I and Pipe II, respectively, revealing that the binding of alpha-CD-Pipe I was stronger than alpha-CD-Pipe II. The K(d1) and K(d2) values were 9.81 x 10(-4) mol L(-1) and 1.11 x 10(-7) (mol L(-1))(2) for 1:1 and 1:2 complexes of Pipe I with beta-CD, respectively. The K(d) values obtained from fluorescence spectroscopy were in agreement with those from ESI-MS titration.
Incidences of H1N1 viral infections in Mainland China are collected by the Ministry of Health, the Peoples Republic of China. The number of confirmed cases and the timing of these outbreaks from May 13 to July 22, 2009 were obtained and subjected to a novel mathematical model to simulate the infection profile (time vs number). The model was predicated upon the grey prediction theory which allows assignment of future trends using limited numbers of data points. During the period of our analysis, the number of confirmed H1N1 cases in Mainland China increased from 1 to 1772. The efficiency of our model to simulate these data points was evaluated using Sum of squares of error (SSE), Relative standard error (RSE), Mean absolute deviation (MAD) and Average relative error (ARE). Results from these analyses were compared to similar calculations based upon the grey prediction algorithm. Using our equation, defined herein as equation D-R, results showed that SSE=6742.00, RSE=10.69, MAD=7.07, ARE=2.47% were all consistent with the D-R algorithm performing well in the estimation of future trends of H1N1 cases in Mainland China. Calculations using the grey theory had no predictive value [ARE for GM(1,1)=-104.63%]. To validate this algorithm, we performed a second analysis using new data obtained from cases reported to the WHO and CDC in the US between April 26 and June 8, 2009. In like manner, the model was equally predictive. The success of the D-R mathematical model suggests that it may have broader application to other viral infections among the human population in China and may be modified for application to other regions of the world.
Two short interfering RNAs (siRNA-RdRp1286, siRNA-RdRp1441) and one short interfering RNA (siRNA-OCP117), targeted to the RNA dependent RNA polymerase (RdRp) gene and outer capsid protein (OCP) gene of Grass carp reovirus (GCRV) respectively, were chemically synthesized and transfected into the CIK cells by lipofectamine 2000. 6 hours after transfection, the transfected CIK cells were challenged with GCRV. The culture media were collected at 48h post challenge and the virus was titrated in microculture system to evaluate the inhibition effect on GCRV replication mediated by siRNAs. Referring to the mRNA level of housekeeping gene beta-actin, RT-PCR was applied to detect the level of GCRV mRNA in transfected and challenged CIK cells. The results showed that the viral titer (lgTCID50/0. 1mL) in siRNA-RdRp1286, siRNA-RdRp1441 and siRNA-OCP117 transfected CIK cells were 4.41 +/- 0.16, 3.83 +/- 0.44 and 1.94 +/- 0.42 respectively, which were significantly lower than that in virus infection positive control (7.92 +/- 0.52) (P < 0.01). No significant change in viral titer was observed in the group transfected with siRNA negative control after challenged with GCRV (7.50 +/- 0.17, P > 0.05). Compared with the mRNA transcriptional level of beta-actin gene in virus infection positive control, the mRNA levels of GCRV in siRNA-RdRpl 286, siRNA-RdRp1 441 and siRNA-OCP117 transfected CIK cells were reduced significantly and the inhibition rate reached to (82.08 +/- 2.15)%, (89.19 +/- 1.14).% and (92.62 +/- 0.17)%, respectively. The mRNA level of GCRV in the siRNA negative control group had no noticeable change (P > 0 05).
Numeric experiments were performed to study the first and second stability regions and find the optimal configurations of a quadrupole mass filter constructed of circular quadrupole rods with a rectangular wave power supply. The ion transmission contours were calculated using ion trajectory simulations. For the first stability region, the optimal rod set configuration and the ratio r/r(0) is 1.110-1.115; for the second stability region, it is 1.128-1.130. Low-frequency direct current (DC) modulation with the parameters of m = 0.04-0.16 and nu = omega/Omega = 1/8-1/14 improves the mass peak shape of the circular rod quadrupole mass filter at the optimal r/r(0) ratio of 1.130. The amplitude modulation does not improve mass peak shape.
We observed the effects of IKVAV self-assembling peptide nanofiber scaffold (SAPNS) on olfactory ensheathing cells (OECs). The IKVAV molecules were triggered to self-assemble to interconnected nanofibers hydrogel by adjusting pH of solution and adding of DMEM/F12 culture medium. Atomic Force Microscopy (AFM) showed that self-assembly hydrogel was consisted of the interconnected nanofibers, which varied from three nm to five nm in diameter and hundreds nanometer in length. The primary OECs were isolated from rat olfactory bulb and purified by differential adhesion twice. At days 12, the purity of OECs was 85% according to immunostaining of P75 NGFR antibody. OECs were cultured with IKVAV peptide. The adhesion, viability and proliferation of OECs were observed with inverted microscope, Calcein-AM/PI staining and Cell Counting Kit-8. OECs cultured on IKVAV SAPNS grew well and the viable cell count was 95%. IKVAV SAPNS can promote the adhesion of OECs and did no hinder the proliferation of OECs. IKVAV SAPNS nanofiber gel has good biocompatibility and bioactivity for OECs. It can serve as a good nerve tissue engineering scaffold.
An ion trap array (ITA) mass analyzer--a novel ion trap mass analyzer with multiple ion trapping and analyzing channels--was designed and constructed. Its property and performance were investigated and reported in this paper. The ITA was built with several planar electrodes including two parallel printed circuit board (PCB) plates. Each PCB plate was fabricated to several identical rectangular electric strips based on normal PCB fabrication technology and was placed symmetrically to those on the opposite plate. There is no electrode between any two adjacent strips. Every strip was supplied with an rf voltage while the polarity of the voltage applied to the adjacent two strips was opposite. So the electric potential at the central plane between two adjacent strips is zero. Multiple identical electric field regions that contain the dominant quadrupole plus some other high-order fields were produced between the two PCB plates. The multiple identical electric field regions will have the property of ion trapping, ion storage, and mass analysis functions. So an ITA could work as multiple ion trap mass analyzers. It could perform multiple sample ion storage, mass-selected ion isolation, ion ejection, and mass analysis simultaneously. The ITA was operated at both "digital ion trap mode" and "conventional rf mode" experimentally. A preliminary mass spectrum has been carried out in one of the ion trap channels, and it shows a mass resolution of over 1000. Additional functions such as mass-selected ion isolation and mass-selected ion ejection have also been tested. Furthermore, the ITA has a small size and very low cost. An ITA with four channels is less than 30 cm(3) in total volume, and it shows a great promise for the miniaturization of the whole mass spectrometer instrument and high-throughput mass analysis.
By using cell culture and virus infection methods, a new reovirus had been isolated from channel catfish (Ictalurus punctatus) suffered with severe hemorrhage and had been identified as channel catfish reovirus (CCRV) after artificial infection in fish, electron microscopy observation, physical-chemical tests, genomic SDS-PAGE analysis and sequencing. In artificial infection test, the typical symptoms of channel catfish hemorrhage as naturally occurred could be reproduced. The isolated virus could cause typical cytopathic effect in CCO and CCK cell lines. Electron microscopy observation of ultra-thin section samples of CCRV infected CCO and CCK cells revealed that the virus replicated in cytoplasm, arrayed in crystalline, and had a non-enveloped double capsid with a diameter of 60-70 nm. Frozen-thawed, 56 degrees C 1 h, chloroform and ether had no significant effects on CCRV titer, 65 degrees C 1 h could significantly inactivated the viral infectivity. The CCRV genome SDS-PAGE analysis and nuclease sensitivity test showed that the virus genome was the same as that of viruses in Aquareovirudae and consisted of 11 segments of dsRNA assigned into three classes L1, L2, L3; M1, M2, M3 and S1, S2, S3, S4, S5 with a range of size from 0.9 to 4.4 kb. The Cloning and sequencing of the CCRV S4 segment indicated the nucleic acid number of CCRV S4 was 909 bp in length, which was exactly the same as that of GCRV S4 (AF403396) and GSRV S4 (AF403407) segments. The BLAST of CCRV S4 sequence in NCBI GenBank showed that it had a 99% and 90% similarity in sequence to the GCRV S4 and GSRV S4 segments, respectively.
Incidence and mortality due to tuberculosis (TB) have been decreasing worldwide. Given that TB is a cosmopolitan disease, proper surveillance and evaluation are critical for controlling dissemination. Herein, mathematical modeling was performed in order to: 1) demonstrate a correlation between the incidence of TB in HIV-free patients in the US and Germany, and their corresponding mortality rates; 2) show the utility of the newly developed D-R algorithm for analyzing and predicting the incidence of TB in both countries; and 3) inform us on population death rates due to TB in HIV-negative patients. Using data published by the World Health Organization between 1990 and 2009, the relationship between incidence and mortality that could not be ascribed to HIV infection was evaluated. Using linear, quadratic and cubic curves, we found that a cubic function provided the best fit with the data in both the US (Y = 2.3588+2.2459X+61.1639X(2)-60.104X(3)) and Germany (Y = 1.9271+9.4967X+18.3824X(2)-10.350X(3)) where the correlation coefficient (R) between incidence and mortality was 0.995 and 0.993, respectively. Second, we demonstrated that fitted curves using the D-R model were equal to or better than those generated using the GM(1,1) algorithm as exemplified in the relative values for Sum of Squares of Error, Relative Standard Error, Mean Absolute Deviation, Average Relative Error, and Mean Absolute Percentage Error. Finally, future trends using both the D-R and the classic GM(1,1) models predicted a continued decline in infection and mortality rates of TB in HIV-negative patients rates extending to 2015 assuming no changes to diagnosis or treatment regimens are enacted.
The rectilinear ion trap (RIT), as a simplified linear ion trap, has shown great potential in the field of portable mass spectrometers for its simple structure and easy manufacture. In this study, the new ceramic-based rectilinear ion trap (cRIT) was constructed, and the performance and geometry optimization of a series of cRITs were examined.
Cardiac fibrosis is a hallmark of heart disease and plays a vital role in cardiac remodeling during heart diseases, including hypertensive heart disease. Hexarelin is one of a series of synthetic growth hormone secretagogues (GHSs) possessing a variety of cardiovascular effects via action on GHS receptors (GHS-Rs). However, the role of hexarelin in cardiac fibrosis in vivo has not yet been investigated. In the present study, spontaneously hypertensive rats (SHRs) were treated with hexarelin alone or in combination with a GHS-R antagonist for 5 wk from an age of 16 wk. Hexarelin treatment significantly reduced cardiac fibrosis in SHRs by decreasing interstitial and perivascular myocardial collagen deposition and myocardial hydroxyproline content and reducing mRNA and protein expression of collagen I and III in SHR hearts. Hexarelin treatment also increased matrix metalloproteinase (MMP)-2 and MMP-9 activities and decreased myocardial mRNA expression of tissue inhibitor of metalloproteinase (TIMP)-1 in SHRs. In addition, hexarelin treatment significantly attenuated left ventricular (LV) hypertrophy, LV diastolic dysfunction, and high blood pressure in SHRs. The effect of hexarelin on cardiac fibrosis, blood pressure, and cardiac function was mediated by its receptor, GHS-R, since a selective GHS-R antagonist abolished these effects and expression of GHS-Rs was upregulated by hexarelin treatment. In summary, our data demonstrate that hexarelin reduces cardiac fibrosis in SHRs, perhaps by decreasing collagen synthesis and accelerating collagen degradation via regulation of MMPs/TIMP. Hexarelin-reduced systolic blood pressure may also contribute to this reduced cardiac fibrosis in SHRs. The present findings provided novel insights and underscore the therapeutic potential of hexarelin as an antifibrotic agent for the treatment of cardiac fibrosis.
Autoantibodies against the second extracellular loop of ?(1) -adrenergic receptor (?(1) -AA) not only contribute to increased susceptibility to heart failure, but also play a causative role in myocardial remodeling through their catecholamine-like effects via binding with the ?(1) -adrenergic receptor. The current study was designed to determine whether ?(1) -AA isolated from the sera of heart failure patients could cause TNF-? secretion from the murine macrophage-like cell line RAW264.7. Blood samples were collected from 40 patients who had suffered heart failure, as well as from 40 healthy subjects. The titer of ?(1) -AA and the level of TNF-? were detected using ELISA. The effect of ?(1) -AA on murine macrophage-like cell line RAW264.7 proliferation was detected by CCK-8 kits and CFSE assay. Western blot assay was used to analyze the expression of phospho-VASP. ?(1) -AA appeared more frequently in patients with heart failure than in healthy subjects. The ?(1) -AA isolated from heart failure patients promoted an increase of TNF-? levels, which could be completely blocked by the selective ?(1) -adrenergic receptor antagonist metoprolol and the second extracellular loop of ?(1) -adrenergic receptor (?(1) -AR-EC(II) ), but only partially inhibited by PKA inhibitor H89. Furthermore, the ?(1) -AA could enhance the proliferation of RAW264.7 cells in vitro. Meanwhile, the expression of phospho-VASP was markedly increased in the presence of ?(1) -AA. These results demonstrate for the first time that the ?(1) -AA isolated from heart failure patients could bind with ?(1) -AR on the surface of RAW264.7 cells, causing the release of TNF-? largely in a PKA-dependent fashion.
Various mechanical stresses can induce apoptosis of nucleus pulposus (NP) cells and intervertebral disc (IVD) degeneration in vivo, but the underlying molecular mechanism by which the number of NP cells is decreased in degenerated IVD is still not elucidated. The purpose of this study was to investigate whether the mitochondrial pathway is involved in compression-induced apoptosis of rabbit NP cells. The compression apparatus was used to investigate the effect of the compression in this process at one magnitude (1.0 MPa) for 6, 12, 18, 24 and 36 h. Cell viability was measured by cell counting kit-8. Apoptosis rate was analyzed by flow cytometry and the morphologic changes in apoptosis cells were observed by the phase-contrast microscopy and Hoechst 33258 staining. The apoptosis-related gene and protein synthesis, such as Bax, Bcl-2 and Caspase-3, was analyzed by real-time polymerase chain reaction and Western-blot, respectively. Mitochondrial function was evaluated by analyzing the mitochondrial permeability transition pore (MPTP), as well as reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). The results indicated that compression at the magnitude of all time points induced apoptosis of rabbit NP cells in a time-dependent manner, and the cell viability was reduced significantly. Furthermore, the compression at this level profoundly suppressed the functions of the mitochondria such as the opening of MPTP, the excessive production of ROS and the decreased MMP. Our findings suggest that the compression-induced IVD degeneration is mediated, at least in part, via the mitochondrial apoptotic pathway in NP cells.
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