Aim： To investigate the action of isothiafludine （NZ-4）, a derivative of bis-heterocycle tandem pairs from the natural product leucamide A, on the replication cycle of hepatitis B virus （HBV） in ...vitro and in vivo. Methods： HBV replication cycle was monitored in HepG2.2.15 cells using qPCR, qRT-PCR, and Southern and Northern blotting. HBV protein expression and capsid assembly were detected using Western blotting and native agarose gel electrophoresis analysis. The interaction of pregenomic RNA （pgRNA） and the core protein was investigated by RNA immunoprecipitation. To evaluate the anti-HBV effect of NZ-4 in vivo, DHBV-infected ducks were orally administered NZ-4 （25, 50 or 100 mg.k~l{1-1） for 15 d. Results： NZ-4 suppressed intracellular HBV replication in HepG2.2.15 cells with an IC~o value of 1.33 pmol/L, whereas the compound inhibited the cell viability with an IC5o value of 50.4 pmol/L. Furthermore, NZ-4 was active against the replication of various drug- resistant HBV mutants, including 3TC/ETV-dual-resistant and ADV-resistant HBV mutants. NZ-4 （5, 10, and 20 pmol/L） concentration- dependently reduced the encapsidated HBV pgRNA, resulting in the assembly of replication-deficient capsids in HepG2.2.15 cells. Oral administration of NZ-4 dose-dependently inhibited DHBV DNA replication in the DHBV-infected ducks. Conclusion： NZ-4 inhibits HBV replication by interfering with the interaction between pgRNA and HBcAg in the capsid assembly process thus increasing the replication-deficient HBV capsids. Such mechanism of action might provide a new therapeutic strategy to combat H BV infection.
AIM：To investigate the utility of Beclin-1 and LC3,two autophagy-related proteins,in predicting the cetuximab efficacy in advanced colorectal cancer（ACRC） . METHODS：The data of 85 patients with ACRC ...treated at the Sun Yat-sen University Cancer Center from March 1,2005 to December 31,2008 were studied,including 45 cases treated with cetuximab-containing chemotherapy and 40 cases treated with non-cetuximab-containing chemotherapy.Beclin-1 and LC3 expression was evaluated by immunohistochemistry,and KRAS status was evaluated by polymerase chain reaction. RESULTS：Beclin-1 and LC3 expression in ACRC wassignificantly correlated（r=0.44,P〈0.01）;however,LC3 was more highly expressed in cancerous tissues than in normal tissues（Z=-2.63,P〈0.01） .In the cetuximab-containing chemotherapy group,patients with low LC3 expression had higher objective response rates（ORRs） than those with high LC3 expression（52.9%vs 17.9%,P=0.01） ,and patients with low Beclin-1 expression had a longer median progressionfree survival（PFS） than their counterparts with higher Beclin-1 expression（9.0 mo vs 3.0 mo,P=0.01） . However,neither of these predictive relationships was detected in the group treated with non-cetuximabcontaining chemotherapy.Patients with wild-type KRAS had higher ORRs（42.3%vs 9.1%,P=0.049） and disease control rates（DCRs）（73.1%vs 36.4%,P= 0.035） ,and longer median PFS（5.5 mo vs 2.5 mo,P= 0.02） than those with mutant KRAS in the cetuximabcontaining chemotherapy group.Neither Beclin-1（P= 0.52） nor LC3（P=0.32） expression was significantly correlated with KRAS status. CONCLUSION：Patients with low Beclin-1 expression had a longer PFS than those with high Beclin-1 expression,and patients with low LC3 expression had a higher ORR in ACRC patients treated with cetuximab-containing chemotherapy.
Colorectal cancer (CRC) is one of the most common malignancies worldwide. The incidence of CRC in the Chinese population has increased dramatically during the last two decades; however, nonrandom ...chromosomal alterations in Chinese patients have not been described. In the present study, comparative genomic hybridization (CGH) was applied to detect recurrent chromosome alterations in 26 primary colorectal carcinomas and 21 colorectal adenomas from Chinese patients. In CRC, several recurrent chromosomal changes were found, including gains of 8q (14/26 cases, 54%), 20q (54%), 3q (50%), 13q (50%), 5p (46%), 7p (42%), 7q (42%), and 12p (38%) and losses of 18q (65%) and 17p (42%). From comparison with previous CGH studies, the frequent gains of 3q and 12p might be distinctive occurrences in Chinese patients. The distribution of frequently found chromosomal alterations in different locations was studied. The gain of 20q was more frequently found in colon cancer (
P<0.01) and the gain of 12p was more frequently found in rectal cancer. Chromosomal alterations were found in 19/21 of adenomas; the most frequent chromosomal alteration was the loss of 18q (9/21 cases, 43%). These recurrent alterations provide several starting points for the isolation of candidate oncogenes and tumor suppressor genes.
AIM： To explore the effect of recombinant human interleukin-11 （rhIL-11） on the expressions of interleukin-11 receptor α-chain （IL-11Rα） and an additional signal transducer glycoprotein 130 （gp130） ...in intestinal epithelium cell line-6 （IEC-6） after neutron irradiation.
METHODS： Cultured IEC-6 cells were exposed to 4.0Gy neutron and treated with 100 ng/mL rhIL-11 12 h prior to or immediately after irradiation. The apoptosis and necrosis rates and expressions of IL-11Rα and gp130 were observed by flow cytometry, immunohistochemistry, Western blot and image analysis.
RESULTS： The apoptosis rate of IEC-6 cells was increased by irradiation at 6 h （P 〈 0.01）, IL-11 stimulation resulted in a decreased apoptosis rate in irradiated IEC-6 cells （P 〈 0.05）. In normal control IEC-6 cells, intense immunoreactivity of IL-11Rα was located within the cell membrane and cytoplasm. The level of IL-11Rα expression significantly decreased at 6 h after irradiation （P 〈 0.01） and restored at 24 h after irradiation. In IEC-6 cells treated with both radiation and rhIL-11, the level of IL- 11Rα expression was higher than that of irradiated cells （P 〈 0.05）. When it came to gp130 protein, it was located in the cytoplasm of IEC-6 cells. After irradiation, we found a progressive decrease in the expression of gp130 protein （P 〈 0.05） in 48 hours post-radiation, while in rhIL-11-stimulated cells, it came back to normal level at 24 h after irradiation and decreased at 48 h, but was still higher than that of only irradiated cells （P 〈 0.05）.
CONCLUSION： rhIL-11 can protect IEC-6 cells from neutron irradiation. The protective effect of rhIL-11 might be connected with its ability to up-regulate the expressions of specific ligand-binding subunit IL-11Rα and signal-transducing subunit gp130.
Through a serious application of an overlapping mesh, vortex-induced vibration （VIV） of low-mass-rationale cylinders was computed in the range of 1.0x 103〈Re〈2.0x104. An overlapping mesh is more ...controllable to deal with the dynamic mesh since there is no necessity to regenerate grids in this complete computational domain. Only boundary nodes are utilized to dispose of all steps each time. It is discovered that the cross-flow amplitudes can increase by approximately 30% in the resonance area when the in-line degree of freedom is taken into account. But the cross-flow amplitudes do not have any change outside the resonance area. In its mass ratio （m＊= mass of cylinder/mass of displaced water） ranging from 1.0 to 40, the ratios of in-line amplitudes to cross-flow amplitudes decrease with the increasing m＊, especially as m＊〈2.5, the ratios will be larger than 10%. Moreover, the phase differences between in-line displacements and cross-flow displacements also reduce as m＊ increases. However, the correlation coefficients between displacements at two directions are so random even a bit low. With regards to vortex mode, the ＇2S＇ mode and the ＇2P＇ mode are very applicable to the present work. Effect of Re is also investigated, this paper aims to prove that the ratios of amplitudes between two directions have few relations with Re, and then the relationship between relative amplitudes and mass ratios can be decoded hereof.
Aim： Carbonaceous dots （CDs）, which have been used for diagnosis, drug delivery and gene delivery, are accumulated in heart at high concentrations. To improve their biocompatibility, polyethylene ...glycol-modified CDs （PEG-CDs） were prepared. In this study we compared the cardiac toxicity of CDs and PEG-CDs in mouse and zebrafish models.
Methods： Mice were intravenously treated with CDs （size： 4.9 nm, 5 mg·kg^-1·d^-1） or PEG-CDs （size： 8.3 nm, 5 mg·kg^-1·d^-1） for 21 d. Their blood biochemistry indices, ECG, and histological examination were examined for evaluation of cardiac toxicity. CDs or PEG-CDs was added in incubator of cmlc2 transgenic Zebrafish embryos at 6 hpf, and the shape and size of embryos＇ hearts were observed at 48 hpf using a fluorescent microscope. Furthermore, whole-mount in situ hybridization was used to examine the expression of early cardiac marker gene （clml2） at 48 hpf. Results： Administration of CDs or PEG-CDs in mice caused mild, but statistically insignificant reduction in serum creatine kinase （CK） and lactate dehydrogenase （LDH） levels detected at 7 d, which were returned to the respective control levels at 21 d. Neither CDs nor PEG-CDs caused significant changes in the morphology of heart cells. Administration of CDs, but not PEG-CDs, in mice caused marked increase of heart rate. Both CDs and PEG-CDs did not affect other ECG parameters. In the zebrafish embryos, addition of CDs （20 pg/mL） caused heart development delay, whereas addition of CDs （80 pg/mL） led to heart malformation. In contrast, PEG-CDs caused considerably small changes in heart development, which was consistent with the results from the in situ hybridization experiments. Conclusion： CDs causes greater cardiac toxicity, especially regarding heart development. Polyethylene glycol modification can attenuate the cardiac toxicity of CDs.
Effect of cerium （Ce^3＋） on the growth, photosynthesis and antioxidant enzyme system in rape seedlings （Brassica juncea L.） exposed to two levels of UV-B radiation （T1： 0.15 W/m^2 and T2：0.35 W/m^2） ...was studied by hydroponics under laboratory conditions. After 5 d of UV-B treatment, the aboveground growth indices were obviously decreased by 13.2%-44. 1%（T1） and 21.4%-49.3% （T2）, compared to CK, and except active absorption area of roots, the belowground indices by 14.1%-35.6%（T1） and 20.3%-42.6% （T2）. For Ce＋UV-B treatments, the aboveground and belowground growth indices were decreased respectively by 4.1%-23.6%, 5.2% -23.3%（Ce＋T1） and 10.8%-28.4%, 7.0%-27.8%（Ce＋T2）, lower than those of UV-B treatments. The decrease of growth indices appeared to be the result of changes of physiological processes. Two levels of UV-B radiation induced the decrease in chlorophyll content, net photosynthesis rate, transpiration rate, stomatal conductance and water use efficiency by 11.2%-25.9%（T1） and 20.9%- 56.9%（T2）, whereas increase in membrane permeability and activities of antioxidant enzymes including superoxide dismutase（SOD）, catalase （CAT） and peroxidase （POD） by 6.9%, 22.8%, 21.5%, 9.5%（T1） and 36.6%, 122.3%, 103.5%, 208.9%（T2）, respectively. The reduction of the photosynthetic parameters in Ce＋UV-B treatments was lessened to 3.2%-13.8%（Ce＋T1） and 4.9%-27.6%（Ce＋T2）, and the increase of membrane permeability and activities of antioxidant enzymes except POD in the same treatments were lessened to 2.4%, 8.4%, 6.6%（Ce＋T1） and 30.1%, 116.7%, 75.4%（Ce＋T2）. These results indicate that the regulative effect of Ce on photosynthesis and antioxidant enzymatic function is the ecophysiological basis of alleviating the suppression of UV-B radiation on growth of seedlings. Furthermore, the protective effect of Ce on seedlings exposed to TI level of UV-B radiation is superior to T2 level.
Hematological traits, which are important indicators of immune function in animals, have been commonly examined as biomarkers of disease and disease severity in humans and animals. Genome-wide ...significant quantitative trait loci (QTLs) provide important information for use in breeding programs of animals such as pigs. QTLs for hematological parameters (hematological traits) have been detected in pig chromosomes, although these are often mapped by linkage analysis to large intervals making identification of the underlying mutation problematic. Single nucleotide polymorphisms (SNPs) are the common form of genetic variation among individuals and are thought to account for the majority of inherited traits. In this study, a genome-wide association study (GWAS) was performed to detect regions of association with hematological traits in a three-generation resource population produced by intercrossing Large White boars and Minzhu sows during the period from 2007 to 2011. Illumina PorcineSNP60 BeadChip technology was used to genotype each animal and seven hematological parameters were measured (hematocrit (HCT), hemoglobin (HGB), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), red blood cell count (RBC) and red blood cell volume distribution width (RDW)). Data were analyzed in a three step Genome-wide Rapid Association using the Mixed Model and Regression-Genomic Control (GRAMMAR-GC) method. A total of 62 genome-wide significant and three chromosome-wide significant SNPs associated with hematological parameters were detected in this GWAS. Seven and five SNPs were associated with HCT and HGB, respectively. These SNPs were all located within the region of 34.6-36.5 Mb on SSC7. Four SNPs within the region of 43.7-47.0 Mb and fifty-five SNPs within the region of 42.2-73.8 Mb on SSC8 showed significant association with MCH and MCV, respectively. At chromosome-wide significant level, one SNP at 29.2 Mb on SSC1 and two SNPs within the region of 26.0-26.2 Mb were found to be significantly associated with RBC and RDW, respectively. Many of the SNPs were located within previously reported QTL regions and appeared to narrow down the regions compared with previously described QTL intervals. In current research, a total of seven significant SNPs were found within six candidate genes SCUBE3, KDR, TDO, IGFBP7, ADAMTS3 and AFP. In addition, the KIT gene, which has been previously reported to relate to hematological parameters, was located within the region significantly associated with MCH and MCV and could be a candidate gene. These results of this study may lead to a better understanding of the molecular mechanisms of hematological parameters in pigs.
Background：Non-Hodgkin lymphoma is the fourth most common malignant tumors in children,Burkitt lymphoma （BL） accounts for 30-50％ of all pediatric lymphomas.The aim of this study was to investigate ...the clinicopathologic features,immunophenotype,Epstein-Barr virus （EBV） infection and c-myc gene rearrangement of sporadic BL in children.Methods：Ninety-two cases of pediatric BL were retrospectively analyzed for clinical features,immunohistochemistry,EBV-encoded RNA （EBER） status by in situ hybridization and c-myc gene rearrangement by fluorescence in situ hybridization.Results：In the 92 cases,male is predominant in sex distribution （M：F =3.38：1）.The average age at diagnosis was 4.97 years.Polypoid BL showed a lower clinical stage （P =0.002）,and advanced clinical stage and low serum albumin level at diagnosis were associated with poor outcome （P =0.024 and 0.053,respectively）.The positive expression of CD10,B-cell lymphoma-6,MUM1 and EBER were 95.7％ （88 cases）,92.4％ （85 cases）,22.8％ （21 cases）,41.3％ （38 cases）,respectively.The expression of MUM1 were not associated with EBV infection status （P =1.000）.c-myc gene rearrangement was detected in 94.6％ （87/92）.Clinical treatment information for 54 cases was collected,21 patients died of tumor after surgery alone,33 patients received surgery and chemotherapy,and of which six patients died shortly afterwords （MUM 1 positive expression in 3 cases,P =0.076）.Conclusions：The anatomical location,growth pattern and serum albumin level of BL were associated with biological behavior.MUM1 may be a potential adverse prognostic marker,and not associated with EBV infection status.
The concept of entransy developed in recent years can describe the heat transport ability. This paper extends this concept to the open thermodynamic system and defines the concept of enthalpy ...entransy. The entransy balance equation of steady open thermodynamic systems, as well as the concept of entransy loss, is developed. The entransy balance equation is applied to analyzing and discussing the air standard cycle. It is found that the entransy loss rate can describe the change in net power output from the cycle but the entropy generation rate cannot when the heat absorbed by the working medium is from the combustion reaction of the gas fuel. When the working medium is heated by a high temperature stream, both the maximum entransy loss rate and the minimum entropy generation rate correspond to the maximum net power output from the cycle. Hence, the concept of entransy loss is an appropriate figure of merit that describes the cycle performance.
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