Nitric oxide induces monosaccharide accumulation through enzyme S-nitrosylation.

Nitric oxide (NO) is extensively involved in various growth processes and stress responses in plants; however, the regulatory mechanism of NO-modulated cellular sugar metabolism is still largely unknown. Here, we report that NO significantly inhibited monosaccharide catabolism by modulating sugar metabolic enzymes through S-nitrosylation (mainly by oxidizing dihydrolipoamide, a cofactor of pyruvate dehydrogenase). These S-nitrosylation modifications led to a decrease in cellular glycolysis enzymes and ATP synthase activities as well as declines in the content of acetyl coenzyme A, ATP, ADP-glucose and UDP-glucose, which eventually caused polysaccharide-biosynthesis inhibition and monosaccharide accumulation. Plant developmental defects that were caused by high levels of NO included delayed flowering time, retarded root growth and reduced starch granule formation. These phenotypic defects could be mediated by sucrose supplementation, suggesting an essential role of NO-sugar cross-talks in plant growth and development. Our findings suggest that molecular manipulations could be used to improve fruit and vegetable sweetness.

Mitochondrion-Permeable Antioxidants to Treat ROS-Burst-Mediated Acute Diseases.

Reactive oxygen species (ROS) play a crucial role in the inflammatory response and cytokine outbreak, such as during virus infections, diabetes, cancer, cardiovascular diseases, and neurodegenerative diseases. Therefore, antioxidant is an important medicine to ROS-related diseases. For example, ascorbic acid (vitamin C, VC) was suggested as the candidate antioxidant to treat multiple diseases. However, long-term use of high-dose VC causes many side effects. In this review, we compare and analyze all kinds of mitochondrion-permeable antioxidants, including edaravone, idebenone, α-Lipoic acid, carotenoids, vitamin E, and coenzyme Q10, and mitochondria-targeted antioxidants MitoQ and SkQ and propose astaxanthin (a special carotenoid) to be the best antioxidant for ROS-burst-mediated acute diseases, like avian influenza infection and ischemia-reperfusion. Nevertheless, astaxanthins are so unstable that most of them are inactivated after oral administration. Therefore, astaxanthin injection is suggested hypothetically. The drawbacks of the antioxidants are also reviewed, which limit the use of antioxidants as coadjuvants in the treatment of ROS-associated disorders.

Determining Optimal Strategies to Reduce Maternal and Child Mortality in Rural Areas in Western China: an Assessment Using the Lives Saved Tool.

China, as a whole, is about to meet the Millennium Development Goals for reducing the maternal mortality ratio (MMR) and infant mortality rate (IMR), but the disparities between rural area and urban area still exists. This study estimated the potential effectiveness of expanding coverage with high impact interventions using the Lives Saved Tool (LiST). It was found that gestational hypertension, antepartum and postpartum hemorrhage, preterm birth, neonatal asphyxia, and neonatal childhood pneumonia and diarrhea are still the major killers of mothers and children in rural area in China. It was estimated that 30% of deaths among 0-59 month old children and 25% of maternal deaths in 2008 could be prevented in 2015 if primary health care intervention coverage expanded to a feasible level. The LiST death cause framework, compared to data from the Maternal and Child Mortality Surveillance System, represents 60%-80% of neonatal deaths, 40%-50% of deaths in 1-59 month old children and 40%-60% of maternal deaths in rural areas of western China.

Antiviral and antitumor activities of the lectin extracted from Aspidistra elatior.

Lectins, a group of highly diverse proteins of non-immune origin and are ubiquitously distributed in plants, animals and fungi, have multiple significant biological functions, such as anti-fungal, anti-viral and, most notably, anti-tumor activities. A lectin was purified from the rhizomes of Aspidistra elatior Blume, named A. elatior lectin (AEL). In vitro experiments showed that the minimum inhibitory concentrations of AEL against the vesicular stomatitis virus, Coxsackie virus B4, and respiratory syncytial virus were all the same at about 4 µg/mL. However, AEL was ineffective against the Sindbis virus and reovirus-1. AEL also showed significant in vitro antiproliferative activity towards Bre-04, Lu-04, HepG2, and Pro-01 tumor cell lines by increasing the proportion of their sub-G1 phase. However, AEL failed to restrict the proliferation of the HeLa cell line. Western blotting indicated that AEL induced the upregulation of cell cycle-related proteins p53 and p21. The molecular basis and species-specific effectiveness of the anti-proliferative and anti-viral potential of AEL are discussed.

[The method and efficacy for screening neonatal tetanus in high risk areas in China].

OBJECTIVES: To establish a method for screening neonatal tetanus (NT) in high risk areas in China using multi-sources data. METHODS: We adopted six NT-related indicators from National Notifiable Disease Report System (NNDRS) and National Maternal and Child Health Annual Report System, to calculate weighted high-risk score at prefecture level in 2010 and 2011. And we selected the top 30 high risk cities, and compared the scores with the actual NT incidence ranking and WHO scoring. RESULTS: The highest areas distributed in the Southwest of China with poor and minority population, and the Southeast part with high density of migrants. In the leading 30 prefectures with high score between the methods of weighted high-risk scoring and reported NT incidence ranking, there were 8 different. In comparison of the results of the methods of weighed high-risk scoring and WHO scoring, 276 prefectures in 340 distributed were divided into the same ranking groups, with Kappa coefficient 0.56 (P < 0.01). The Chi-Square association coefficient was 0.74 (P < 0.01), which showed a high correlation. But there were 10 different prefectures in the leading 36 prefectures between the two methods. CONCLUSION: The weighted scoring method included several possible factors influencing NT incidence and took their weights into consideration. Thereby, compared with WHO scoring method, this method could be more appropriate for the reality in China.

A single leaf of Camellia oleifera has two types of carbon assimilation pathway, C(3) and crassulacean acid metabolism.

The C(4) plants, whose first product of photosynthetic CO(2) fixation is a four-carbon acid, have evolved independently many times. Crassulacean acid metabolism (CAM) is a biological mechanism known to exhibit some C(4) characteristics such as the C(3) cycle during daylight and demonstrates the C(4) cycle at night. There are also various C(3)-CAM intermediates, whose CAM pathway can be induced by environmental changes. However, neither fungus-induced CAM nor Theaceae CAM have been reported previously. Here, we show that CAM could be generated by fungus infection in Camellia oleifera Abel. young leaves, even at a location of a single leaf where the upper part had been transformed into a succulent one, while the lower part remained unchanged. The early photosynthetic products of dark-grown C. oleifera succulent leaves were malate, whereas C. oleifera normal leaves and light-grown succulent leaves incorporated most of (14)C into the primary photosynthetic product 3-phosphoglycerate. Camellia oleifera succulent leaves have a lower absolute δ(13)C value, much lower photorespiration rates and lower transpiration rates during the day than those of C. oleifera normal leaves. Like a typical CAM plant, stomata of C. oleifera succulent leaves closed during the daylight, but opened at night, and therefore had a detectable CO(2) compensation point in darkness. Net photosynthetic rates (P(n)) fluctuated diurnally and similarly with stomatal aperture. No light intensity saturation could be defined for C. oleifera succulent leaves. C(4) key enzymes in C. oleifera succulent leaves were increased at both the transcriptional/translational levels as well as at the enzyme activity level.

Red blood cell extrudes nucleus and mitochondria against oxidative stress.

Mammal red blood cells (erythrocytes) contain neither nucleus nor mitochondria. Traditional theory suggests that the presence of a nucleus would prevent big nucleated erythrocytes to squeeze through these small capillaries. However, nucleus is too small to hinder erythrocyte deformation. And, there is no sound reason to abandon mitochondria for the living cells. Here, we found that mammal erythrocyte reactive oxygen species (ROS) levels kept stable under diabetes, ischemia reperfusion, and malaria conditions or in vitro sugar/heme treatments, whereas bird erythrocyte ROS levels increased dramatically in these circumstances. Nuclear and mitochondrial extrusion may help mammal erythrocytes to better adapt to high-sugar and high-heme conditions by limiting ROS generation.

Mg-protoporphyrin, haem and sugar signals double cellular total RNA against herbicide and high-light-derived oxidative stress.

Cellular total RNA level is usually stable, although it may increase gradually during growth or seed germination, or decrease gradually under environmental stresses. However, we found that plant cell RNA could be doubled within 48 h in response to herbicide-induced Mg-protoporphyrin and heme accumulation or a high level of sugar treatment. This rapid RNA multiplication is important for effective cellular resistance to oxidative stress, such as high-light and herbicide co-stress conditions, where the plastid-signalling defective mutant gun1 shows an apparent phenotype (more severe photobleaching). Hexokinase is required for sugar-induced RNA multiplication. While both sugar and Mg-protoporphyrin IX require plastid protein GUN1 and a nuclear transcription factor ABI4, haem appears to function through an independent pathway to control RNA multiplication. The transcription co-factor CAAT binding protein mediates the rapid RNA multiplication in plant cells in all the cases.

Preparation and characterization of a novel recombinant human parathyroid hormone (1-34) analog (Gly1-Gln26-rhPTH(1-34)) with enhanced biological activity.

A recombinant human parathyroid hormone (rhPTH) fragment (Gly1-Gln26-rhPTH(1-34)) which contains two amino acids substitutions (Gly1 and Gln26) was acquired through Escherichia coli expression system using a soluble fusion protein strategy. The soluble fusion protein MBP-Gly1-Gln26-rhPTH(1-34) was harvested after purification by Phenyl-Sepharose F.F and Q-Sepharose F.F chromatographies. Following tobacco etch virus (TEV) protease cleavage and further purification by SP-Sepharose F.F chromatography, 30.8 mg/L Gly1-Gln26-rhPTH(1-34) without tag was obtained with high purity up to 99%. Cyclic AMP (cAMP) stimulation assay suggested that Gly1-Gln26-rhPTH(1-34) could increase the biological activity by up to 13.89% and 6.34%. After daily subcutaneous injection (for 13 weeks) of 5, 10 and 20 microg of Gly1-Gln26-rhPTH(1-34)/1000g body weight, the mean Bone Material Density (BMD) of ovariectomized (OVXed) rats increased to 7.95-30.54% and 1.98-23.32%, compared to control-vehicle group (OVX, P<0.001) and sham- operated group (SHAM, P<0.01), respectively.

Apoptosis-inducing effect and structural basis of Polygonatum cyrtonema lectin and chemical modification properties on its mannose-binding sites.

Polygonatum cyrtonema Lectin (PCL), which is classified as a monocot mannose-binding lectin, has received great regards for its uniquely biological activities and potentially medical applications in cancer cells. This paper was initially aimed to study apoptosis of PCL on Hela cells. Thus, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method was carried out. Through observation of cell morphologic changes and Lactate dehydrogenase (LDH) activity-based cytotoxicity assays, PCL induced HeLa cell apoptosis in a dose-dependent manner. To further gain structural basis, multiple alignments, homology modeling and docking experiments were performed to analyze the correlation between its biological activities and mannose-binding sites. Eventually, considering docking data, chemical modification properties on the three mannose-binding sites were analyzed by a series of biological experiments (e.g., hemagglutinating and mitogenic activity assays, fluorescence and Circular Dichrosim (CD) spectroscopy) to profoundly identify the role of some key amino acids in the structure-function relationship of PCL.

Hemagglutinating activity and conformation of a lactose-binding lectin from mushroom Agrocybe cylindracea.

A lactose-binding lectin (Agrocybe cylindracea Lectin, ACL) purified from fruiting bodies of the mushroom A. cylindracea was investigated to determine the hemagglutinating activity and conformation changes after chemical modification, removal of metal ion and treatment at different temperatures and pH. ACL agglutinated both rabbit and human erythrocytes and its hemagglutinating activity could be inhibited by lactose. This lectin was stable in the pH range of 6-9 and temperature up to 60 degrees C. Fluorescence quenching and modification of tryptophan residues indicated that there were about two tryptophan residues in ACL molecule and one of them might be located on the surface, while the other was buried in the hydrophobic shallow groove near the surface. Chemical modification of serine/threonine and histidine showed that the partial necessity of these residues for the hemagglutinating activity of ACL. However, modifications of arginine, tyrosine and cysteine residues had no effect on its agglutinating activity.