Membrane-Anchoring, Comb-Like Pseudopeptides for Efficient, pH-Mediated Membrane Destabilization and Intracellular Delivery

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A Virus-Mimicking, Endosomolytic Liposomal System for Efficient, pH-Triggered Intracellular Drug Delivery

A novel multifunctional liposomal delivery platform has been developed to resemble the structural and functional traits of an influenza virus. Novel pseudopeptides were prepared to mimic the pH-responsive endosomolytic behavior of influenza viral peptides through grafting a hydrophobic amino acid, l-phenylalanine, onto the backbone of a polyamide, poly­(l-lysine isophthalamide), at various degrees of substitution. These pseudopeptidic polymers were employed to functionalize the surface of cholesterol-containing liposomes that mimic the viral envelope. By controlling the cholesterol proportion as well as the concentration and amphiphilicity of the pseudopeptides, the entire payload was rapidly released at endosomal pHs, while there was no release at pH 7.4. A pH-triggered, reversible change in liposomal size was observed, and the release mechanism was elucidated. In addition, the virus-mimicking nanostructures efficiently disrupted the erythrocyte membrane at pH 6.5 characteristic of early endosomes, while they showed negligible cytotoxic effects at physiological pH. The efficient intracellular delivery of the widely used anticancer drug doxorubicin (DOX) by the multifunctional liposomes was demonstrated, leading to significantly increased potency against HeLa cancer cells over the DOX-loaded bare liposomes. This novel virus-mimicking liposomal system, with the incorporated synergy of efficient liposomal drug release and efficient endosomal escape, is favorable for efficient intracellular drug delivery

Photopatterned Thiol Surfaces for Biomolecule Immobilization

The ability to pattern small molecules and proteins on artificial surfaces is of importance for the development of new tools including tissue engineering, cell-based drug screening, and cell-based sensors. We describe here a novel “caged” thiol-mediated strategy for the fabrication of planar substrates patterned with biomolecules using photolithography. A thiol-bearing phosphoramidite (3-(2′-nitrobenzyl)thiopropyl (NBTP) phosphoramidite) was synthesized and coupled to a hydroxyl-terminated amorphous carbon substrate. A biocompatible oligo(ethylene glycol) spacer was used to resist nonspecific adsorption of protein and DNA and enhance flexibility of attached biomolecules. Thiol functionalities are revealed by UV irradiation of NBTP-modified surfaces. Both the surface coupling and photodeprotection were monitored by Polarization Modulation Fourier Transform Infrared Reflection Absorption Spectroscopy (PM-FTIRRAS) and X-ray Photoelectron Spectroscopy (XPS) measurements. The newly exposed thiols are chemically very active and react readily with a wide variety of groups. A series of molecules including biotin, DNA, and proteins were attached to the surfaces with retention of their biological activities, demonstrating the utility and generality of the approach

Additional file 2 of Trends in avoidable hospitalizations in a developed City in eastern China: 2015 to 2018

Additional file 2: Appendix

Reprocessable Silyl Ether-Based Dynamic Covalent Poly(dimethylsiloxane) Networks with Superb Thermal Stability and Creep Resistance

Introducing covalent adaptable networks (CANs) into polydimethylsiloxane (PDMS) elastomers is an effective approach to solving the recycling issue of thermoset PDMS materials. However, CANs generally exhibit favorable dynamic properties to achieve efficient recycling, which leads to poor thermal stability and creep resistance. Herein, we successfully constructed dynamic silyl ether-based networks within the PDMS system by incorporating thermally stable silyl ether linkages, resulting in reprocessable PDMS elastomers with excellent mechanical properties, remarkable thermal stability, and desirable creep resistance. Compared with the samples without silyl ether-based networks, the prepared PDMS elastomer presented a 70 °C increase in T50 (the temperature at 50% weight loss), reaching as high as 635 °C. Meanwhile, after 10 reprocessing cycles, the mechanical properties of the prepared elastomer can still be almost completely restored, demonstrating superior reprocessability. More importantly, owing to the thermal stability of silyl ether-based networks, the prepared PDMS elastomer exhibited a desirable creep resistance at 120 °C. Therefore, the rational construction of dynamic silyl ether-based networks within the PDMS system can achieve an effective balance between thermal stability and recyclability

Pupillometric and blink measures of diverse task loads: Implications for working memory models

Background: Inconsistent observations of pupillary response and blink change in response to different specific tasks raise questions regarding the relationship between eye measures, task types and working memory (WM) models. On the one hand, studies have provided mixed evidence from eye measures about tasks: pupil size has mostly been reported to increase with increasing task demand while this expected change was not observed in some studies, and blink rate has exhibited different trends in different tasks. On the other hand, a WM model has been developed to integrate a component to reconcile recent findings that the human motor system plays an important role in cognition and learning. However, how different tasks correlate with WM components has not been experimentally examined using eye activity measurements. Aims: The current study uses a four-dimensional task load framework to bridge eye measures, task types and WM models. Sample: Twenty participants (10 males, 10 females; Age: M = 25.8, SD = 7.17) above 18 years old volunteered. All participants had normal or corrected to normal vision with contact lenses and had no eye diseases causing obvious excessive blinking. Methods: We examined the ability of pupil size and blink rate to index low and high levels of cognitive, perceptual, physical and communicative task load. A network of the four load types and WM components was built and analysed to verify the necessity of integrating a physical task-related component into the WM model. Results: Results demonstrate that pupil size can index cognitive load and communicative load but not perceptual or physical load. Blink rate can index the level of cognitive load but is best at discriminating perceptual tasks from other types of tasks. Furthermore, pupil size measurement of the four task types was explained better during structural and factor analysis by a WM model that integrates a movement-related component. Conclusions: This research provides new insights into the relationship between eye measures, task type and WM models and provides a comprehensive understanding from which to predict pupil size and blink behaviours in more complex and practical tasks

Additional file 1 of Trends in avoidable hospitalizations in a developed City in eastern China: 2015 to 2018

Additional file 1: Appendix

Approximate model and algorithms for precast supply chain scheduling problem with time-dependent transportation times

This paper focuses on the precast supply chain scheduling problem with time-dependent transportation time to minimise the total weighted tardiness (PSCSP_TDT |TWT). In the problem, an order sequence and several job sequences are to be determined simultaneously. At first, through in-depth analysis of problem structure and real data from a precast manufacturer, we approximate the problem into a three-stage order scheduling problem by combining the seven production stages into one differentiation stage, and then explore some useful properties of the schedules for the approximate problem. Subsequently, to solve the small instances for the PSCSP_TDT |TWT, we propose an approximate model-based hybrid dynamic programming and heuristic (AMHDPH) and obtain a lower bound as a by-product of the algorithm. For dealing with medium-or large instances, with considering the complexity of the problem, we propose four approximate model-based hybrid iterated greedy (AMHIG) algorithms by integration of constructive heuristics, structural properties of solutions, an iterated greedy, and a correction heuristic. Comprehensive computational results show that the AMHDPH generates tight lower bounds for small instances and solves the most of small instances to optimality within 60 seconds. Whereas the best AMHIG generates feasible solutions with an average optimality gap below 5 percent for around 70 percent instances.</p

DataSheet1_Causal associations between CD40/CD40L and aortic diseases: A mendelian randomization study.PDF

Background: CD40 and CD40L have been reported as associated with aortic dissection (AD) and aortic aneurysm (AA), but the causality of the associations has not been established yet.Methods: We conducted a two-sample Mendelian randomization (MR) study to assess the causal inference between CD40/CD40L and aortic diseases including AD and AA. The instrumental variables (IVs) for CD40 and CD40L were selected from a high-quality protein quantitative trait loci dataset released by a genomic study involving 30,931 individuals of European ancestry. The genome-wide association studies summary statistics for AD and AA were from the FinnGen Release 7, with 288638 controls for all outcomes of interests, 680 cases for AD and 6,092 cases for AA, also from European ancestry. For AA subtypes, there were 5,881 cases of thoracic AA (TAA) and 2,434 cases of abdominal AA (AAA) respectively. Inverse-variance weighted and Wald ratio were applied for calculating causal estimates. Horizontal pleiotropy and heterogeneity were assessed using MR-Egger regression analysis and Cochran Q test, respectively. Leave-one-out analyses were further performed.Results: Three single-nucleotide polymorphisms (SNPs) for CD40 and one SNP for CD40L were selected as IVs. We found genetic proxied CD40 levels inversely associated with the risk of AD (odds ratio [OR]: 0.777, 95% confidence interval [CI]: 0.618–0.978, p = 0.031) and AA (OR: 0.905, 95% CI: 0.837–0.978, p = 0.012), consistent across TAA (both p Conclusion: Our MR study provides evidence supporting the causal association between CD40 and the reduced risks of both AD and AA.</p

Passive Focusing of Single Cells Using Microwell Arrays for High-Accuracy Image-Activated Sorting

Sorting single cells from a population was of critical importance in areas such as cell line development and cell therapy. Image-based sorting is becoming a promising technique for the nonlabeling isolation of cells due to the capability of providing the details of cell morphology. This study reported the focusing of cells using microwell arrays and the following automatic size sorting based on the real-time recognition of cells. The simulation first demonstrated the converged streamlines to the symmetrical plane contributed to the focusing effect. Then, the influence of connecting microchannel, flowing length, particle size, and the sample flow rate on the focusing effect was experimentally analyzed. Both microspheres and cells could be aligned in a straight line at the Reynolds number (Re) of 0.027–0.187 and 0.027–0.08, respectively. The connecting channel was proved to drastically improve the focusing performance. Afterward, a tapered microwell array was utilized to focus sphere/cell spreading in a wide channel to a straight line. Finally, a custom algorithm was employed to identify and sort the size of microspheres/K562 cells with a throughput of 1 event/s and an accuracy of 97.8/97.1%. The proposed technique aligned cells to a straight line at low Reynolds numbers and greatly facilitated the image-activated sorting without the need for a high-speed camera or flow control components with high frequency. Therefore, it is of enormous application potential in the field of nonlabeled separation of single cells