Effect of Hydrophobic Chain Length on the Stability and Guest Exchange Behavior of Shell-Sheddable Micelles Formed by Disulfide-Linked Diblock Copolymers

Reduction-responsive micelles hold enormous promise for application as drug carriers due to the fast drug release triggered by reducing conditions and high anticancer activity. However, the effect of hydrophobic chain length on the stability and guest exchange of reduction-responsive micelles, especially for the micelles formed by diblock copolymers containing single disulfide group, is not fully understood. Here, shell-sheddable micelles formed by a series of disulfide-linked copolymer poly­(ethylene glycol)-<i>b</i>-poly­(ε-caprolactone) (PEG–SS–PCL) containing the same chain length of PEG but different chain lengths of hydrophobic block PCL were prepared and well characterized. The influence of the chain length of hydrophobic PCL block on the stability and guest exchange of PEG–SS–PCL micelles was studied by the use of both dynamic laser light scattering (DLS) and fluorescence resonance energy transfer (FRET). The results show that longer PCL chains lead to a slower aggregation rate and guest exchange of micelles in the aqueous solutions containing 10 mM dithiothreitol (DTT). The cell uptake of the shell-sheddable PEG–SS–PCL micelles in vitro shows that the amount of internalization of dyes loaded in PEG–SS–PCL micelles increases with the chain length of hydrophobic PCL block investigated by flow cytometric analysis and confocal fluorescence microscopy

Mutations in hepatitis B virus polymerase are associated with the postoperative survival of hepatocellular carcinoma patients

<div><p>Proofreading deficiencies of hepatitis B virus polymerase result in frequent DNA mutations in the hepatitis B virus genome. Here, we performed sequencing analysis of the hepatitis B virus polymerase gene to assess its association with the postoperative survival in 92 patients with HBV-related hepatocellular carcinoma by using the Kaplan–Meier method. The 2525, 2733, 2738, 2768, 2946, 3063, 3066, 3109, 31, 529, 735, 939, 1078, 1137, 1383, 1461, 1485, 1544, and 1613 mutation sites were identified as being associated with HCC outcomes by the log-rank test. After adjusting for clinical characteristics by using the Cox hazard model, site 31 (relative risk, 8.929; 95% confidence interval, 3.433–23.22; <i>P</i> = 0.000) in the spacer domain and sites 529 (relative risk, 5.656; 95% confidence interval, 1.599–19.999; <i>P</i> = 0.007) and 1078 (relative risk, 3.442; 95% confidence interval, 1.070–11.068; <i>P</i> = 0.038) in the reverse transcriptase domain of hepatitis B virus polymerase were identified as independent predictors of postoperative survival in hepatitis B virus related hepatocellular carcinoma. The mutations at the 31 (Ser314Pro), 529 (Asp480Asn), and 1078 (Ser663Ala) sites all resulted in amino acid changes in hepatitis B virus polymerase and were associated with shortened life-span. The 31 and 529 sites were located in the overlapping region for the PreS and S genes but did not induce amino acid substitution in these two regions. Our finding of the correlation between hepatitis B virus DNA polymerase mutations and hepatocellular carcinoma survival will help identify the patients subgroup with poor prognosis, and help the clinicians to refine the therapeutic decision individualized.</p></div

Multivariate analysis of the clinical factors associated with postoperative survival in HBV-HCC patients.

<p>Multivariate analysis of the clinical factors associated with postoperative survival in HBV-HCC patients.</p

Distribution of mutation frequency in the HBV polymerase region.

<p>The square indicates the mutations associated with survival in HBV-HCC, as determined by univariate analysis using the log-rank test; the rhombus indicates mutations that are not associated with HBV-HCC.</p

Univariate and multivariate analysis of the clinical factors associated with postoperative survival in HBV-HCC patients.

<p>Univariate and multivariate analysis of the clinical factors associated with postoperative survival in HBV-HCC patients.</p

Univariate analysis of HBV polymerase gene mutations associated with postoperative survival in patients with HBV-HCC.

<p>Univariate analysis of HBV polymerase gene mutations associated with postoperative survival in patients with HBV-HCC.</p

Schema of the polymerase region and overlapping preS, S, and X regions.

<p>Schema of the polymerase region and overlapping preS, S, and X regions.</p

Image_1_The Two Translationally Controlled Tumor Protein Genes, CsTCTP1 and CsTCTP2, Are Negative Modulators in the Cucumis sativus Defense Response to Sphaerotheca fuliginea.pdf

<p>Pathogen stress often significantly decreases cucumber production. However, knowledge regarding the molecular mechanism and signals of cucumber disease resistance is far from complete. Here, we report two translationally controlled tumor protein genes, CsTCTP1 and CsTCTP2, that are both negative modulators in the Cucumis sativus defense response to Sphaerotheca fuliginea. Subcellular localization analysis showed that CsTCTP1 and CsTCTP2 were both localized in the cytoplasm. Expression analysis indicated that the transcript levels of CsTCTP1 and CsTCTP2 were linked to the degree of cucumber resistance to S. fuliginea. Transient overexpression of either CsTCTP1 or CsTCTP2 in cucumber cotyledons impaired resistance to S. fuliginea, whereas silencing of either CsTCTP1 or CsTCTP2 enhanced cucumber resistance to S. fuliginea. The relationship of several defense-related genes and ABA and target of rapamycin (TOR) signaling pathway-related genes to the overexpressing and silencing of CsTCTP1/CsTCTP2 in non-infested cucumber plants was investigated. The results indicated that CsTCTP1 participates in the defense response to S. fuliginea by regulating the expression of certain defense-associated genes and/or ABA signaling pathway-associated genes, and CsTCTP2 participates through regulating the expression of TOR signaling pathway-associated genes. Our findings will guide enhancing the resistance of cucumber to powdery mildew.</p

Composite of Hierarchically Porous N‑Doped Carbon/Carbon Nanotube with Greatly Improved Catalytic Performance for Oxygen Reduction Reaction

In this work, a series of catalysts were synthesized by pyrolysis of in situ formed hybrids of metal–organic framework MIL-101­(Fe) and polypyrrole (PPy) nanotube followed by acid etching. The obtained catalysts exhibit composite structure of hierarchically porous carbon and carbon nanotube, which endowed the catalysts high surface areas, plenty of active sites and high conductivity, and thus high electrocatalytic performance on oxygen reduction reaction (ORR). The optimum onset and half-wave potential of +17 and −116 mV (vs Ag/AgCl) have been obtained, respectively, which is even 4 and 12 mV positive than commercial Pt/C (20%) in alkaline. The catalyst also exhibits superior long-term stability and durability against methanol. Kinetic investigations have shown that ORR on the catalyst tended to a more effective 4e^– dominant transfer process, which makes it a promising nonprecious metal ORR catalyst for fuel cell