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Objective@#To synthesize a folic acid (FA)-modified pH-sensitive nanomicelle containing sorafenib (SF) and superparamagnetic iron oxide (SPIO), and to access its visibility in MRI and anti-cancer efficacy on hepatocellular carcinoma (HCC) in vitro.@*Methods@#The copolymer FA-PEG-Pasp (DBA/DIP) of FA, poly(ethylene glycol), N,N-dibutylethylenediamine and N,N-diisopropylethylenediamine grafted poly (L-aspartic acid) were prepared. SF and SPIO were encapsulated inside the copolymer to synthesize the targeting micelle FA-PEG-PAsp (DBA/DIP)-SPIO/SF (FPASS). The folate-free micelle[PEG-PAsp (DBA/DIP)-SPIO/SF (PASS)] was used as nontargeting micelle. The physicochemical properties and drug release behavior of the micelles were analyzed. MRI of HepG2 cells incubated with FPASS and PASS with different Fe concentrations and Prussian blue staining of cells treated with the micelles (Fe concentration of 20 μg/ml) was performed to assess the drug delivery capability and imaging function of the micelles. For the FA competitive inhibition assay in these experiments, HepG2 cells were pre-treated with an excess amount of free FA prior to the incubation with FPASS. Cell viability, cell apoptosis, cell cycle and tube formation assays were conducted for evaluating the anti-HCC effects of the micelles. Comparison between groups was analyzed by one-way ANOVA, and multiple comparisons correction was performed by LSD test.@*Results@#The diameters of FPASS and PASS were (102.3±5.2) nm and (107.1±5.7) nm, respectively; the δ potentials of them were (29.7±1.6) mV and (31.5±1.4) mV, respectively. The T2 relaxivity of both the micelles was (5.2±0.4) ml·μg-1·s-1, which was much higher than that of water soluble Fe3O4 nanoparticles [(2.3±0.1) ml·μg-1·s-1; F=76.45, P<0.01]. SF released from the micelles was much faster at pH5.0 than at pH7.4, which indicated that the micelles had a pH-triggered drug release behavior. MRI of HepG2 cell samples revealed the signal intensity on T2WI images and the T2 value on T2-map images decreased with the increasing Fe concentrations in the micelles. At the same Fe concentration (5, 10, 20 and 40 μg/ml), the cells of FPASS group exhibited a more significant decrease in T2 signal intensity and T2 value compared with those of PASS group or FA competitive inhibition group (F=8.69, 14.03, 27.27, 32.25 and 19.80, 45.76, 113.20, 66.80; P<0.01). Prussian blue staining verified the existing of SPIO in the cytoplasm of cells. Compared with PASS, FPASS presented significantly higher anticancer effects on inducing apoptosis, causing G0/G1 phase arrest on HepG2 cells and inhibiting tube formation on human umbilical vein endothelial cells (t=7.905, 4.399 and 3.454, respectively; P<0.01).@*Conclusions@#The pH-sensitive nanomicelle FPASS was successfully constructed. This micelle possessed a hypersensitive MRI-visible function and a targeting SF delivery capability which may contribute to a significant anti-HCC effect.
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Objective To investigate positive picobirnaviruses(PVBs)infection and its association with unex-plained diarrhea in children. Methods From January to December 2015,the Clinical Microbiology Testing Center of Xuzhou Central Hospital as the sampling location,7 PVB reverse transcription - polymerase chain reaction(RT - PCR)- positive fecal samples with diarrhea were collected from children under 6 years old and 4 samples from healthy chil-dren were obtained and all the samples were analyzed by viral metagenomics to investigate the relationship between PVBs and diarrhea in children. Phylogenetic analysis of RdRp in the isolated PVB sequences was carried out to clarify the relationship between PVB classification and diarrhea. Results All the 7 diarrhea feces contained high titers of PVB sequences,while 3 of the controls were negative,and 1 with low titers of PVB. RdRp analysis was carried out on the iso-lated PVB sequences,which displayed that 7 RdRp sequences caming from 7 fecal samples separately,so named ChXz- 1 to ChXz - 7 respectively. Phylogenetic analysis based on the predicted amino acid sequences of RdRp from this study and whole RdRp sequences available in the GenBank database indicated that the 7 RdRp sequences belonged to 3 genogroups,in which ChXz - 1,ChXz - 2,ChXz - 3 belonging to genogroup Ⅰ,ChXz - 4,ChXz - 5,ChXz - 7 belong-ing to genogroup Ⅱ,and ChXz - 6 belonging to genogroup Ⅲ. Conclusions PVBs might be the cause of diarrhea in children in this study,and all the 3 different PVBs may lead to diarrhea.
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The present study was an effort to determine the bacterial diversity of soils in Mingyong Glacier located at the Meili Snow Mountains of southwestern China. Mingyong Glacier has different climatic zones within a very narrow area, and bacterial community diversity in this low temperature area remains largely unknown. In this study, soil samples were collected from four different climatic zones: M11A [dry warm valley], M14 [forest], M15 [grass land], and M16 [glacier zones]. Phylogenetic analysis based on 16S rRNA gene V6 hypervariable region showed high bacterial abundance in the glacier. The number of Operational Taxonomic Units ranged from 2.24×10[3] to 5.56×10[3] in soil samples. Statistical analysis of 16S rRNA gene clone libraries results showed that bacterial diversity in zones M11A, M14 and M16 are higher than in zone M15. The bacterial community structures are clearly distinguishable, and phylogenetic analysis showed that the predominant phyla were Proteobacteria, Deinococcus-Thermus, Firmicutes, Actinobacteria, and Nitrospirae in Mingyong Glacier. Seventy-nine different orders from four zones have been isolated. Bacterial diversity and distribution of bacterial communities related to the anthropogenic perturbations in zone [M15] were confirmed by diversity index analysis, and the diversity index of other three zones was satisfactory through this analysis software. The results suggest that bacterial diversity and distribution analyses using bacterial 16S rRNA gene V6 hypervariable region were successful, and bacterial communities in this area not only had the same bacterial phyla compared to other glaciers but also had their own rare species
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Objective To longitudinally analyze microstructural white matter changes in high risk mild cognitive impairment (MCI) patients with DTI.Methods Structural MRI,DTI and psychometric analyses were performed in 102 individuals with 1 year follow-up.At the end of the follow-up,11 participants were diagnosed with MCI (CN-MCI group),while 91 participants were classified as cognitively stable (CN-stable group).The differences of fractional anisotropy (FA) and mean diffusivity (MD) between the two groups were analyzed,and the relationship with MCIs and cognitive ability was observed with multivariate logistic regression analysis.Results At the baseline assessment,MD of CN-MCI group increased in fornix and left parahippocampal gyrus white matter compared with those of CN-stable group (P＜0.05).For 1-year follow-up reassessment,the MD of CN-MCI group increased in the fornix,left parahippocampal gyrus white matter,left eingulum and splenium,while FA of CN-MCI group reduced in fornix and left parahippocampal gyrus white matter compared with those of CN-stable group (P＜0.05).Multivariate Logistic regression analysis showed that MD of the fornix could be a predictor of conversion from a high risk MCI to MCI,and MD of left parahippocampus gyrus white matter was a risk factor for increased CDR scores.Conclusion For high-risk MCI individuals,microstructural white matter changes may be used as potential imaging biomarkers in the early phase of AD.