Abstract
Direct‐acting antivirals (DAAs) have become an effective first‐line treatment for chronic hepatitis C (CHC), and the fixed‐dose combination of sofosbuvir (SOF) and velpatasvir (VEL) is one ...of the most important pangenotypic DAA regimen according to present treatment guideline. The association between SOF‐based regimens and renal toxicity remains controversial. A total of 953 patients including 130 with estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73m
2
and 823 with eGFR > 60 mL/min/1.73m
2
receiving SOF/VEL therapy for 12 weeks were enrolled in this study. The eGFR was assessed at baseline, end of treatment (EOT), and 12 weeks after completion of the therapy (end of follow‐up, EOF). The eGFR in patients with eGFR ≤ 60 mL/min/1.73m
2
increased from baseline (47.89 ± 10.25 mL/min/1.73m
2
) to EOT (51.65 ± 15.92;
P
< .001) and EOF (51.51 ± 14.46 mL/min/1.73m
2
;
P
< .05). The eGFR in patients with eGFR > 60 mL/min/1.73m
2
at baseline (91.52 ± 22.06 mL/min/1.73m
2
) was lower at EOT (90.37 ± 22.3;
P
< .05), with no difference between EOT and EOF (
P
= .06). Multivariable analysis showed that a higher serum albumin level was associated with a lower risk of eGFR decrease at EOT, and the patients with baseline eGFR > 60 mL/min/1.73m
2
were associated with a higher risk of eGFR decrease at EOF. The rates of sustained virologic response 12 weeks after treatment cessation (SVR12) were 99.2% in per‐protocol analysis, and the most common adverse events were fatigue (4.7%), abdominal discomfort (4.5%), and skin itching (3.7%). In conclusion, renal function improved after the SOF/VEL treatment in patients with CHC and chronic kidney disease. Thus, SOF/VEL was safe, effective, and tolerable in these patients.
A Pd/PCy3/Ag2CO3 (Cy = cyclohexyl) catalytic system was found to promote decarboxylative arylation through the combination of decarboxylation and C–H bond functionalization. This protocol features a ...good substrate scope of aromatic carboxylic acids as well as a broad range of functional groups and provides the products in high yields.
A Pd/PCy3/Ag2CO3 catalytic system promoting decarboxylative arylation through the combination of decarboxylation and C–H bond functionalization is reported. This protocol features a good substrate scope of aromatic carboxylic acids containing a broad range of functional groups and provides the products in high yields; Cy = cyclohexyl, tfa = trifluoroacetate.
Lo, W-T., Purcell, J. E., Hung, J-J., Su, H-M., and Hsu, P-K. 2008. Enhancement of jellyfish (Aurelia aurita) populations by extensive aquaculture rafts in a coastal lagoon in Taiwan. – ICES Journal ...of Marine Science, 65: 453–461.Blooms of the moon jellyfish, Aurelia aurita, often occur in coastal waters that are heavily affected by human construction, such as harbours. Tapong Bay is a hypertrophic lagoon in southwestern Taiwan that was studied between August 1999 and September 2004. The removal of extensive oyster-culture rafts in June 2002 provided a “natural” experiment to examine the effects of aquaculture on processes and communities in the lagoon. The removal caused many changes in the ecosystem, including increases in flushing, light penetration, dissolved oxygen, salinity, chlorophyll a, primary production, and zooplankton, but decreases in nutrients, periphyton, and dramatically reduced populations of bivalves, zooplanktivorous fish, and jellyfish (A. aurita). We conclude that environmental and trophic conditions were favourable for jellyfish throughout the study period. Therefore, we believe that aquaculture rafts enhanced jellyfish populations by three probable mechanisms: the rafts provided substrate and shading for the larval settlement and polyp colony formation, and the rafts restricted water exchange in the lagoon. Aquaculture is increasing rapidly in Asia, and the problems associated with jellyfish may also increase.
A newly identified arbitrium communication system regulates the lysis-to-lysogeny decision in a
bacteriophage. This system contains an arbitrium hexapeptide as a signal, the cellular receptor AimR, ...and the lysogenic negative regulator AimX. AimR specifically targets the downstream DNA to activate
gene expression. The arbitrium peptide binds to AimR, inhibiting its DNA-binding to promote phage lysogeny. Recently, we and other groups have elucidated how arbitrium peptide sensed by AimR. However, the molecular mechanisms of DNA recognition by AimR and the regulation of its DNA-binding activity by the peptide remain largely unknown. Here, we report the crystal structure of the AimR-DNA complex at 2.1 Å resolution. The N-terminal HTH motif recognizes the palindromic DNA sequence, buttressed by interactions between positively charged residues and the DNA phosphate groups. The DNA-bound AimR assembles a more closed dimer than the peptide-bound form. Single-molecule FRET and crosslinking assays revealed that the AimR protein samples both open and closed conformations in solution. Arbitrium peptide binding induces a closed-to-open conformational change of AimR, eliminating DNA targeting. Our structural and functional analysis provides new insights into the DNA recognition mechanism of AimR and its regulation by the arbitrium peptide in the context of phage lysis-lysogeny decisions.
碩士
環球科技大學
環境資源管理所
101
Abstract
The investigation of performance of plantation in the Kingmen area was studied. The 30 plots in Kingmen were the plantation area including Casuarina equisetifolia, ...Acacia confusa, Liquidambar formosana, Fraxinus griffithii, etc. The application of matrix cluster analysis (MCA) classified the Kingmen area into Pinus luchuensis, Acacia confusa, Casuarina equisetifolia, Fraxinus griffithii, Cinnamomum camphora, Pinus elliottii Engelm, and Liquidambar formosana. The analysis for the structure of population indicated a main shape of closed bell-shaped in each plot of Kingmen area, excluding the planCasuarina equisetifolia of plot 4,5, 12, 14, and 15, those were showed the inverse J-shaped or the closed L-shaped was presented.
The application of BFA classified the health factor into three levels. In the Kingmen area, 17 plots in 56.7% of the whole area showed in the healthy level, 10 in slightly unhealthy and 3 in unhealthy. Fraxinus griffithii and Pinus elliottii Engelm were the spec
The aim of this study was to investigate the species composition and distribution of fish larvae in relation to hydrographic conditions in the waters surrounding Taiwan Island (TI) in February 2003. ...In total, 242 kinds of fish larvae belonging to 127 genera and 75 families were recognized. Among these, 109 taxa were identified to the family or genus level, others to the species level. The 12 predominant types, which constituted 71% of the total fish larvae, were Engraulis japonica, Scomber sp., Diaphus spp., Benthosema pterotum, Carangoides ferdau, Embolichthys mitsukurii, Maurolicus sp., unidentified Myctophidae, Gonostoma gracile, Trichiurus lepturus, unidentified Gobiidae, and Myctophum asperum. The distribution of fish larvae showed a clear association with water masses around TI, with higher abundances and lower species richness northwest of TI where the China Coastal Current prevails, and lower abundances and higher species diversity east of TI where the Kuroshio Current dominates. Cluster analysis distinguished three station groups and four species groups, and the distribution patterns of fish larvae also corresponded to hydrographic conditions. The total abundances of fish larvae and eight of the 12 predominant taxa showed significant and positive correlations with zooplankton abundance, which suggests that food source might be a key factor determining the abundance and distribution of fish larvae during the winter.
Temperate phages dynamically switch between lysis and lysogeny in their full life cycle. Some Bacillus-infecting phages utilize a quorum-sensing-like intercellular communication system, the ...“arbitrium,” to mediate lysis-lysogeny decisions. However, whether additional factors participate in the arbitrium signaling pathway remains largely elusive. Here, we find that the arbitrium signal induces the expression of a functionally conserved operon downstream of the arbitrium module in SPbeta-like phages. SPbeta yopM and yopR (as well as phi3T phi3T_93 and phi3T_97) in the operon play roles in suppressing phage lytic propagation and promoting lysogeny, respectively. We further focus on phi3T_93 and demonstrate that it directly binds antitoxin MazE in the host MazF/MazE toxin-antitoxin (TA) module and facilitates the activation of MazF’s toxicity, which is required for phage suppression. These findings show events regulated by the arbitrium system and shed light on how the interplay between phages and the host TA module affects phage-host co-survival.
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•Phage arbitrium system induces the expression of a downstream operon•Two genes in this operon influence phage lytic/lysogenic infection•Phage YopM (phi3T_93) binds the host MazF/MazE module and activates MazF toxin•MazF/MazE module suppresses phage lytic propagation via abortive infection
Some temperate phages utilize a quorum-sensing-like intercellular communication system, the “arbitrium,” to mediate lysis-lysogeny decisions, but downstream events in the arbitrium signaling pathway remain largely elusive. Cui et al. show that for SPbeta-like phages, an arbitrium-regulated phage protein and a host toxin-antitoxin module together control phage lytic propagation.
The reuse of treated wastewater in agricultural systems could partially help alleviate water resource shortages in developing countries. Treated wastewater differs from fresh water in that it has ...higher concentrations of salts, Escherichia coli and presence of dissolved organic matter, and inorganic N after secondary treatment, among others. Its application could thus cause environmental consequences such as soil salinization, ammonia volatilization, and greenhouse gas emissions. In an incubation experiment, we evaluated the characteristics and effects of water-filled pore space （WFPS） and N input on the emissions of nitrous oxide （N2O） and carbon dioxide （CO2） from silt loam soil receiving treated wastewater. Irrigation with treated wastewater （vs. distilled water） significantly increased cumulative N2O emission in soil （117.97 μg N kg-1）. Cumulative N2O emissions showed an exponentially increase with the increasing WFPS in unamended soil, but the maximum occurred in the added urea soil incubated at 60% WFPS. N2O emissions caused by irrigation with treated wastewater combined with urea-N fertilization did not simply add linearly, but significant interaction （P〈0.05） caused lower emissions than the production of N2O from the cumulative effects of treated wastewater and fertilizer N. Moreover, a significant impact on cumulative CO2 emission was measured in soil irrigated with treated wastewater. When treated wastewater was applied, there was significant interaction between WFPS and N input on N2O emission. Hence, our results indicated that irrigation with treated wastewater should cause great concern for increasing global warming potential due to enhanced emission of N2O and CO2.
Irritable bowel syndrome (IBS) is a common clinical gastrointestinal dysfunction disorders. 5-sertonon (5-hydroxytryptamine, 5-HT) is a very important neurotransmitter, which is involved in ...gastrointestinal motion and sensation. Solute carrier family 6 member 4 (SLC6A4) gene encode serotonin transporter (SERT) which function is to rapidly reuptake the most of 5-HT. Therefore, it is needed to explore the association between SLC6A4 gene polymorphisms and IBS.
119 patients and 238 healthy controls were administrated to detect the SLC6A4 gene polymorphisms including 5-HT-transporter-gene-linked polymorphic region (5-HTTLPR), variable number of tandem repeats (VNTRs) and three selected tag Single Nucleotide Polymorphisms (SNPs) rs1042173, rs3794808, rs2020936 by using polymerase chain reaction (PCR) and TaqMan® SNP Genotyping.
There were significant difference for 5-HTTLPR between IBS and control groups (X2 = 106.168, P<0.0001). In control group, genotypes were mainly L/L (58.4%), however, the genotypes in IBS were S/S (37.8%). The significant difference was shown in D-IBS subjects when compared to the controls (X(2) = 50.850, P<0.0001) for 5-HTTLPR. For STin2 VNTR, rs1042173, rs3794808, and rs2020936 polymorphisms, there were no any significant differences between IBS and control groups. There were no statistical significantly haplotypes for 5-HTTLPR, VNTRs and the three SNPs between IBS and controls.
The S allele in 5-HTTLPR was a susceptible allele with Chinese Han IBS, but other associations of VNTRs, three selected Tag SNPs and positive haplotype with IBS were not found. It is indicated that much research are needed to study the relationship between other polymorphisms in SLC6A4 gene and IBS.
AIM:To investigate the effects of osteopontin(OPN)gene expression knockdown on colon cancer Lovo cells in vitro.METHODS:Four candidate small interfering RNA(siRNA)constructs targeting the OPN gene ...and a scrambled control sequence(NC-siRNA)were synthesized and inserted into a pGPU6/GFP/Neo expression vector.After confirmation by restriction enzyme digestion and DNA sequencing,the recombinant plasmids were subsequently transfected into a human colon cancer cell line(Lovo)using a liposome transfection method.Stably transfected cells were maintained with G418 selection and referred to as Lovo-OPN-1,-2,-3,-4,and Lovo-NC cells.Knockdown efficiency of each of the four siRNA constructs was determined by realtime reverse transcription polymerase chain reaction assays and western blotting,and the construct with the most effective silencing was used for subsequent experiments.Cell proliferation,adhesion,and Matrigel invasion assays were performed to analyze the effects of OPN knockdown in stably transfected Lovo cells.The levels of four angiogenic factors,namely vascular endothelial growth factor(VEGF),matrix metalloproteinase(MMP)-2,MMP-9 and urokinase plasminogen activator were detected by enzyme-linked immunosorbent assays(ELISA).RESULTS:Recombinant vectors containing OPNspecific and scrambled siRNA sequences were successfully constructed and stably transfected into Lovo cells.Compared with the control Lovo and Lovo-NC cells,the levels of OPN mRNA and protein expression in LovoOPN-1,-2,-3,and-4 were significantly reduced(all P<0.05),with the most efficient reduction observed in Lovo-OPN-4 cells(P<0.05).Relative to untransfected Lovo cells,OPN mRNA expression levels in Lovo-NC and Lovo-OPN-4 cells were 1.008±0.067 and 0.160±0.023,respectively.The relative OPN protein expression levels in Lovo,Lovo-NC,and Lovo-OPN-4 cells were 3.024±0.211,2.974±0.630,and 0.121±0.008,respectively.Moreover,transfection with the scrambled sequence had no effect on the expression of OPN.After24,48,72,and 96 h of cultivation,absorption values at 450 nm to assess proliferation of Lovo-OPN-4 cells were 0.210±0.017,0.247±0.024,0.314±0.037,and 0.359±0.043,respectively,which were significantly lower than those of Lovo(0.244±0.031,0.313±0.024,0.513±0.048 and 0.783±0.051)and LovoNC cells(0.241±0.029,0.309±0.022,0.563±0.023,and 0.735±0.067)(all P<0.05).The absorption values at 595 nm,which were measured in a cell adhesion assay,showed that adhesion of Lovo-OPN-4 cells(0.215±0.036)was significantly decreased compared to Lovo(0.490±0.037)and Lovo-NC cells(0.462±0.043)(P<0.05).The number of invasive Lovo-OPN-4 cells(16.1±1.9)was also significantly decreased compared to Lovo(49.9±5.4)and Lovo-NC cells(48.8±4.5)(P<0.05).ELISA assays showed significant reductions in Lovo-OPN-4 cells compared to Lovo and Lovo-NC cells with regard to the expression of VEGF(1687.85±167.84 ng/L vs 2348.54±143.80 ng/L and 2284.39±138.62 ng/L,respectively),MMP-2(2966.07±177.36μg/L vs 4084.74±349.54μg/L and 4011.41±424.48μg/L,respectively),MMP-9(3782.89±300.64μg/L vs5062.90±303.02μg/L and 4986.38±300.75μg/L,respectively)and uPA(1152.69±120.79μg/L vs1380.90±147.25μg/L and 1449.80±189.92μg/L,respectively)(all P<0.05).CONCLUSION:Knockdown of OPN gene expression suppresses colon cancer cell growth,adherence,invasion,and expression of angiogenic factors.
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