Assembly and Reassembly of Polyelectrolyte Complex Formed by Poly(ethylene glycol)-<i>block</i>-poly(glutamate sodium) and S₅R₄ Peptide

The structure and stability of polyelectrolyte complex are controlled not only by electrostatic interaction but also by hydrogen bonding and hydrophobic interaction if they are present. The complexes formed by such multiple interactions should exhibit different responses to the environmental changes, such as ionic strength and pH. In this work, we designed a positively charged peptide S₅R₄, which can interact with poly­(ethylene glycol)-<i>block</i>-poly­(glutamate sodium) (PEG₁₁₄-PGlu₆₄) via electrostatic interaction, hydrogen bonding, and hydrophobic interaction. In deionized water at pH 7.1, the complexes formed by PEG₁₁₄-PGlu₆₄ and S₅R₄ assemble into wormlike micelles, spheres, and even hierarchical “wool balls”, depending on mixing ratio. However, a distinct dissociation–reassembly process is observed when 30 mM NaCl is added to screen the electrostatic interaction. The spheres transform into loose clusters after reassembly. This process is caused by the switch of driving force from electrostatic interaction to hydrogen bonding. Similarly, when the driving force is switched from electrostatic interaction to hydrophobic interaction by increasing solution pH to above 8.7, the original structure quickly dissociates and reassembles into dense aggregates. The rich structures formed by polyelectrolyte complexes and their drastic and sensitive responses to environmental changes are helpful to understand the working mechanism of biomolecules regulated by pH or ion strength

Aggregate Structure in Heavy Crude Oil: Using a Dissipative Particle Dynamics Based Mesoscale Platform

Heavy crude oil consists of thousands of compounds and much of them have a fairly large relative molar mass and complex structure. It is hard to learn the dynamic behavior of this fluid system at all atom models. The present study aims at constructing a mesoscale platform to explore aggregate behavior of asphaltenes in heavy crude oil. The aggregate structure in heavy crude oils was investigated by introducing rigid body fragments, which represents the significant presence of structures of fused aromatic rings in fractions such as asphaltenes and resins into dissipative particle dynamics (DPD). Another pressing task about how to determine the structure of the average model molecules and conservative force parameters was discussed in detail. With some regularity concerning the number of rings, the distribution of side chains and heteroatoms in average model molecules are revealed. Finally, we integrated the modified DPD program, model molecules, and the parameters selected for the preliminarily simulation of the heavy crude oil and emulsion system. The interlayer distance and the number of layers of the well-ordered structure in heavy crude oil are similar to some molecular dynamics works and supported by X-ray and transmission electron microscopy (TEM) experimental data. The relationship between the stability and the mass ratio among components of heavy crude oil is explored, and the result of our simulations fits the regularity <i>Shell</i> once published. In the emulsion system, the surfactant-like feature of asphaltenes and resins are observed. The preliminary simulation results demonstrate the validity of the rotational algorithm and parameters employed and encourage us to extend this platform to study the rheological and colloidal characteristics of heavy crude oils in the future

Shear Effects on Stability of DNA Complexes in the Presence of Serum

The behavior of nanocarriers, even though they are well-defined at equilibrium conditions, is unpredictable in living system. Using the complexes formed by plasmid DNA (pDNA) and K₂₀ (K: lysine), protamine, or polylysine (PLL) as models, we studied the dynamic behavior of gene carriers in the presence of fetal bovine serum (FBS) and under different shear rates, a condition mimicking the internal physical environment of blood vessels. Without shear, all the positively charged complexes bind to the negatively charged proteins in FBS, leading to the formation of large aggregates and even precipitates. The behaviors are quite different under shear. The shear generates two effects: a mechanical force to break down the complex into smaller size particles above a critical shear rate and a stirring effect leading to secondary aggregation of complexes below the critical shear rate. In the studied shear rate from 100 to 3000 s^–1, the mechanical force plays a key role in K₂₀/pDNA and protamine/pDNA, while the stirring effect is dominant in PLL/pDNA. A model study shows that the interfacial tension, the chain density, and the elasticity of the complexes determine their responsiveness to shear force. This study is helpful to understand the fate of drug/gene carriers under physiological conditions. It also gains insight in designing drug/gene carriers with desirable properties for in vivo applications

Clinical Significance of Programmed Death Ligand‑1 and Intra-Tumoral CD8⁺ T Lymphocytes in Ovarian Carcinosarcoma

<div><p>Ovarian carcinosarcoma (OCS) accounts for high mortality and lacks effective therapeutic methods. So far, we lack reliable biomarkers capable of predicting the risk of aggressive course of the disease. Programmed death ligand-1 (PD-L1) is expressed in various tumors, and antibodies targeting its receptor programmed cell death 1 (PD-1) are emerging cancer therapeutics. This study was designed to evaluate the expression of PD-L1 and intratumoral CD8+ T lymphocytes by immunohistochemistry from 19 OCS patients who underwent primary surgery at Fudan University Shanghai Cancer Center. The correlations between PD-L1 expression and CD8+ T lymphocytes as well as the patients’ clinicopathologic characteristics were integrated and statistically analyzed. PD-L1-positive expression was observed in 52.6% of intraepithelial tissues and 47.4% of mesenchymal tissues (p = 0.370). Meanwhile, intraepithelial and mesenchymal CD8+ T lymphocytes were positive in 36.8% and 84.2% of OCS, respectively (p = 0.628). A significantly negative correlation was found between mesenchymal CD8+ T lymphocytes and PD-L1 expression (r = -0.630, p = 0.011). Intraepithelial PD-L1-positive expression was associated only with positive ascitic fluid (p = 0.008). Mesenchymal PD-L1-positive patients had a poorer survival than those with negative expression (p = 0.036). Meanwhile, intraepithelial PD-L1-positive patients had a better survival trend than PD-L1-negative patients, though no statistical significance was found (p = 0.061). There was a better postoperative survival noted in mesenchymal CD8-positive patients (p = 0.024), and allthough a better trend of OS was observed in intraepithelial CD8-positive patients, no statistical significance was found (p = 0.382). Positive tumoral CD8+ T lymphocytes and mesenchymal PD-L1-negative expression seem to be associated with better survival in OCS. It is possible that immunotherapy targeting PD-L1 pathway could be used in OCS.</p></div

Demographic and clinicopathological characteristics of 19 OCS patients.

<p>Demographic and clinicopathological characteristics of 19 OCS patients.</p

Correlations between the expression of PD-Ls or tumor-infiltrating CD8+ lyphocytes and clinicopathological characteristics in ovarian carcinosarcoma (<i>n</i> = 19).

<p>Correlations between the expression of PD-Ls or tumor-infiltrating CD8+ lyphocytes and clinicopathological characteristics in ovarian carcinosarcoma (<i>n</i> = 19).</p

Three-year survival rate of 19 OCS patients according to clinicopathologic characteristics and tumor PD-L1 status (Log-rank).

<p>Three-year survival rate of 19 OCS patients according to clinicopathologic characteristics and tumor PD-L1 status (Log-rank).</p

Kaplan-Meier survival curves of patients with ovarian carcinosarcoma (OCS).

<p>Fig 1A and 1B show the post-operative survival classified according to tumor site (unilateral tumor vs. bilateral tumors) and residual disease (no visible disease vs. visible residual disease), respectively. Patients with bilateral tumors and visible residual disease showed significantly worse prognosis (p = 0.019 and p = 0.027, log-rank test). Fig 1C and 1D show the post operation survival curves between mesenchymal PD-L1-positive and PD-L1-negative expression. Intraepithelial PD-L1-positive patients had a trend of better survival than PD-L1-negative patients (p = 0.061). A significant difference in postoperative prognosis between mesenchymal PD-L1-positive and PD-L1-negative patients was observed (p = 0.036).</p

Facile Synthesis of Nanosized Lithium-Ion-Conducting Solid Electrolyte Li_1.4Al_0.4Ti_1.6(PO₄)₃ and Its Mechanical Nanocomposites with LiMn₂O₄ for Enhanced Cyclic Performance in Lithium Ion Batteries

Nanoparticles of fast lithium-ion-conducting solid electrolyte Li_1.4Al_0.4Ti_1.6(PO₄)₃ (LATP) are prepared by a modified citric-acid-assisted sol–gel method that involves a two-step heat treatment in which the dry gel is calcined first in argon and then in air. The obtained LATP exhibits smaller particle size (down to 40 nm) with a narrower size distribution and less aggregation than LATP prepared by a conventional sol–gel method because of a polymeric network that preserves during LATP crystallization. It has a high relative density of 97.0% and a high room-temperature conductivity of 5.9 × 10^–4 S cm^–1. The as-prepared superfine LATP is further used to composite with a spinel LiMn₂O₄ cathode in lithium ion batteries by simple grinding. This noncoating speckled layer over the LiMn₂O₄ particle surface has a minimal effect on the electronic conductivity of the electrode while offering excellent ionic conductivity. The cycling stability and rate capability of LiMn₂O₄ are greatly improved at both ambient and elevated temperatures. After 100 cycles at 25 and 55 °C, the capacity retentions are 96.0% and 89.0%, respectively, considerably higher than the values of pristine LiMn₂O₄ (61.0% at 25 °C; 51.5% at 55 °C) and mechanical LiMn₂O₄ composite with LATP made by a conventional sol–gel method (85.0% at 25 °C; 71.4% at 55 °C)

Correlation between tumor PD-L1 expression and intratumoral CD8+ T lymphocyte count.

<p>Correlation between tumor PD-L1 expression and intratumoral CD8+ T lymphocyte count.</p