Cordycepin induces cell cycle arrest and apoptosis by inducing DNA damage and up-regulation of p53 in Leukemia cells

Cordycepin, an adenosine analog derived from Cordyceps militaris has been shown to exert anti-tumor activity in many ways. However, the mechanisms by which cordycepin contributes to the anti-tumor still obscure. Here our present work showed that cordycepin inhibits cell growth in NB-4 and U937 cells by inducing apoptosis. Further study showed that cordycepin increases the expression of p53 which promotes the release of cytochrome c from mitochondria to the cytosol. The released cytochrome c can then activate caspase-9 and trigger intrinsic apoptosis. Cordycepin also blocks MAPK pathway by inhibiting the phosphorylation of ERK1/2, and thus sensitizes the apoptosis. In addition, our results showed that cordycepin inhibits the expression of cyclin A2, cyclin E, and CDK2, which leads to the accumulation of cells in S-phase. Moreover, our study showed that cordycepin induces DNA damage and causes degradation of Cdc25A, suggesting that cordycepin-induced S-phase arrest involves activation of Chk2-Cdc25A pathway. In conclusion, cordycepin-induced DNA damage initiates cell cycle arrest and apoptosis which leads to the growth inhibition of NB-4 and U937 cells.     

Antimicrobial Susceptibility and Molecular Mechanisms of Fosfomycin Resistance in Clinical Escherichia coli Isolates in Mainland China

Escherichia coli is one of the most common pathogens in nosocomial and community-acquired infections in humans. Fosfomycin is a broad-spectrum antibiotic which inhibits peptidoglycan synthesis responsible for bacterial cell wall formation. Although low, the exact E. coli susceptibility to fosfomycin as well as the mechanisms of resistance in the population from Mainland China are mostly unknown. 1109 non-duplicate clinical E. coli strains isolated from urine, sputum, blood and pus samples in 20 widely dispersed tertiary hospitals from Mainland China were collected from July 2009 to June 2010, followed by determination of minimum inhibitory concentrations of fosfomycin. Detection of the murA, glpT, uhpT, fosA, fosA ₃ and fosC genes was performed in fosfomycin non-susceptible E. coli strains and conjugation experiments were employed to determine the mobility of fosA ₃ gene. In this study, 7.8% (86/1109) E. coli strains were fosfomycin non-susceptible. Amino acid substitutions in GlpT and MurA were found in six and four E.coli strains, respectively, while the uhpT gene was absent in eighteen E.coli strains. Twenty-nine isolates carried the transferable plasmid with the fosA ₃ gene at high frequencies of around 10⁻⁶ to 10⁻⁷ per donor cell in broth mating. The majority of isolates were susceptible to fosfomycin, showing that the drug is still viable in clinical applications. Also, the main mechanism of E. coli resistance in Mainland China was found to be due to the presence of the fosA ₃ gene.     

Calcium Nodules as a Proxy for Quaternary Paleoclimate Change on China’s Loess Plateau

Different proxies have been used to investigate Quaternary paleoclimate change. Here, we used weathering of calcium nodules in paleosols on China’s Loess Plateau as a proxy for Quaternary paleoclimate changes to provide an alternative indicator of these changes. Paleosol and carbonate nodules were collected from Luochuan and Lantian counties in Shaanxi Province, China. We found that this approach allowed quantitative reconstruction of temperature, rainfall, soil mineral composition, and the effects of weathering and leaching. The changes in carbonate content in the loess and paleosol sequences were controlled by alternating dry and wet climatic conditions. Nodule formation conditions were directly affected by the leaching and migration of elements. The loess and paleosol sequences developed calcium nodules, and their formation was closely related to the rainfall and leaching characteristics of the paleoclimate. The paleoclimate and soil minerals affected the vegetation types and directly influenced changes in the soil. During formation of the calcium nodules, the surface vegetation evolved slowly, and the number of species and quantity of vegetation both decreased.     

Temporal Reliability and Lateralization of the Resting-State Language Network

The neural processing loop of language is complex but highly associated with Broca''s and Wernicke''s areas. The left dominance of these two areas was the earliest observation of brain asymmetry. It was demonstrated that the language network and its functional asymmetry during resting state were reproducible across institutions. However, the temporal reliability of resting-state language network and its functional asymmetry are still short of knowledge. In this study, we established a seed-based resting-state functional connectivity analysis of language network with seed regions located at Broca''s and Wernicke''s areas, and investigated temporal reliability of language network and its functional asymmetry. The language network was found to be temporally reliable in both short- and long-term. In the aspect of functional asymmetry, the Broca''s area was found to be left lateralized, while the Wernicke''s area is mainly right lateralized. Functional asymmetry of these two areas revealed high short- and long-term reliability as well. In addition, the impact of global signal regression (GSR) on reliability of the resting-state language network was investigated, and our results demonstrated that GSR had negligible effect on the temporal reliability of the resting-state language network. Our study provided methodology basis for future cross-culture and clinical researches of resting-state language network and suggested priority of adopting seed-based functional connectivity for its high reliability.