Clostridium novyi-NT in cancer therapy

AbstractThe attenuated anaerobic bacterium Clostridium novyi-NT (C. novyi-NT) is known for its ability to precisely germinate in and eradicate treatment-resistant hypoxic tumors in various experimental animal models and spontaneously occurring canine sarcomas. In this article, we review the therapeutic and toxicologic aspects of C. novyi-NT therapy, key challenges and limitations, and promising strategies to optimize its performance via recombinant DNA technology and immunotherapeutic approaches, to establish C. novyi-NT as an essential tool in cancer therapy

The additions of Nitrogen and Sulfur synergistically decrease the release of Carbon and Nitrogen from litter in a subtropical forest

Atmospheric nitrogen (N) and sulfur (S) deposition in subtropical forests has increased rapidly and the current level is very high, thus seriously affecting nutrient (e.g., N and phosphorus (P)) release from litter. However, the specific effects of S addition and its interaction with N on the release of carbon (C), N, and P from litter in subtropical evergreen broadleaved forests are unclear. Therefore, a two-year field experiment was performed using a litterbag method in a subtropical evergreen broadleaved forest in western China to examine the responses of litter decomposition and nutrient release to the control (CK), added N (+N), added S (+S), and added N and S (+NS) treatments. The results showed that the remaining litter mass, lignin, cellulose, C, N, P, and litter N/P ratio were higher, whereas the litter C/N ratio and soil pH were lower in the fertilization treatments than in CK. The annual decomposition coefficients (k-values) in the +N, +S, and +NS treatments were 0.384 ± 0.002, 0.378 ± 0.002, and 0.374 ± 0.001 year−1, respectively, which were significantly lower than the k-values in CK (0.452 ± 0.005 year−1, p < 0.05). The remaining mass, lignin, cellulose, C, and litter N/P ratio were higher, whereas the soil pH was lower in the +NS treatment than in the +N and +S. The interactive effects of N addition and S addition on the remaining litter lignin, cellulose, C, N, and P; the litter C/N, C/P, and N/P ratios; and the soil pH were significant (p < 0.05). In conclusion, the addition of N and S synergistically decreased the degradation of lignin and cellulose and the release of C and N and increased the litter N/P ratio, suggesting that external N and S inputs synergistically slowed the release of C and N from litter and exacerbated litter P limitation during decomposition in this forest

Responses of soil C, N, and P stoichiometric ratios to N and S additions in a subtropical evergreen broad-leaved forest

Acid deposition from the emission of nitrogen (N) and sulfur (S) has become an important factor affecting the soil nutrient balance and biogeochemical cycling in terrestrial ecosystems. The average levels of N and S deposition in the rainy area of southwestern China from 2008 to 2010 were 9.5 g N m¯² y¯¹ and 19.3 g S m¯² y¯¹, respectively. External additions of N and S fertilizers combined with high levels of acid deposition may affect the soil ecological stoichiometry in the region's widely distributed subtropical evergreen broad-leaved forest. Therefore, we investigated the responses of the soil stoichiometric ratios and enzyme activities to added N (+N), added S (+S), added N and S (+NS), and a control (Ctr) in the 0-20 cm layer in an evergreen broad-leaved forest in the rainy area of southwestern China from April 2013 to April 2015. The results showed that the soil total N (TN) concentration and N/P ratio were higher and the soil organic C (SOC) concentration and C/N ratio were lower in the fertilization treatments than the Ctr, although N and S additions did not significantly alter the soil total P (TP) concentration. The +N, +S, and +NS treatments increased the soil acid phosphatase activity and reduced the soil invertase, cellulase, catalase, and polyphenol oxidase activities. The +N and +NS treatments increased the soil urease activity and reduced soil peroxidase activity. The +S treatment reduced the soil urease activity and did not alter soil peroxidase activity. N and S additions had synergistic decreasing effects on the SOC concentration, C/N ratio, and soil cellulose and catalase activities. Moreover, structural equation models identified that N and S additions regulated the SOC, TN, and TP concentrations via shifting the activities of soil enzymes and the pathways differed between N addition and S addition. In conclusion, N and S additions decreased the SOC concentration, C/N ratio, and most soil C-cycle enzyme activities and increased the TN concentration, N/P ratio, and soil acid phosphatase activity. All these results indicated that external N and S additions combined with acid deposition increased soil N concentrations and exacerbated soil C and P limitations in this forest

Overexpression of an Incw2 gene in endosperm improved yield-related traits in maize

High yield is an eternal goal for crop breeding. Incw2 protein is the enzyme in the metabolic pathway that mobilizes photoassimilated sucrose into numerous reactions of the developing plant seeds, associated with grain yield. In the research, an Incw2 gene driven by 27 kD zein promoter was specifically over-expressed in the endosperm cells of maize inbred line 18-599R by Agrobacterium-mediated genetic transformation. PCR assay displayed that ten of the regenerated plants were integrated with the target gene. By semi-quantitative RT-PCR and invertase activity analysis, five of them showed significantly higher expression of Incw2 transcripts and enzyme activity compared to the wild type. Among them, line 1 stood out because it possessed the highest level of Incw2 mRNA and enzyme activity. The effects of Incw2 over-expression were reflected in the increased chlorophyll content, improved pho¬tosynthesis and delay of leaf senility. In addition, yield-related traits such as ear length, ear diameter, ear weight, grain weight per ear, and hundred-kernel weight appeared to be improved in three of the transformants compared with the wild type. The grain weight per plant of line1 was increased by nearly 10%. The results collectively indicate that it is potentially practical to enhance kernel yield of maize by overexpression of Incw2 in endosperm

Cloning and characterization of miRNAs from maize seedling roots under low phosphorus stress

MicroRNAs (miRNAs) are a class of small, non-coding regulatory RNAs that regulate gene expression by guiding target mRNA cleavage or translational inhibition in plants and animals. In this study, a small RNA library was constructed to identify conserved miRNAs as well as novel miRNAs in maize seedling roots under low level phosphorus stress. Twelve miRNAs were identified by high throughput sequencing of the library and subsequent analysis, two belong to conserved miRNA families (miRNA399b and miRNA156), and the remaining ten are novel and one of latter is conserved in gramineous species. Based on sequence homology, we predicted 125 potential target genes of these miRNAs and then expression patterns of 7 miRNAs were validated by semi-RT-PCR analysis. MiRNA399b, Zma-miR3, and their target genes (Zmpt1 and Zmpt2) were analyzed by real-time PCR. It is shown that both miRNA399b and Zma-miR3 are induced by low phosphorus stress and regulated by their target genes (Zmpt1 and Zmpt2). Moreover, Zma-miR3, regulated by two maize inorganic phosphate transporters as a newly identified miRNAs, would likely be directly involved in phosphate homeostasis, so was miRNA399b in Arabidopsis and rice. These results indicate that both conserved and maize-specific miRNAs play important roles in stress responses and other physiological processes correlated with phosphate starvation, regulated by their target genes. Identification of these differentially expressed miRNAs will facilitate us to uncover the molecular mechanisms underlying the progression of maize seedling roots development under low level phosphorus stress