The ideal nanoscale drug delivery vehicle allows control over the released dose in space and time. We demonstrate that this can be achieved by stealth liposomes comprising self-assembled ...superparamagnetic iron oxide nanoparticles (NPs) individually stabilized with palmityl-nitroDOPA incorporated in the lipid membrane. Alternating magnetic fields were used to control timing and dose of repeatedly released cargo from such vesicles by locally heating the membrane, which changed its permeability without major effects on the environment.
Electron microscopy studies are used to explore the morphology of thin poly(3,4‐ethylenedioxythiophene) and polystyrene sulfonate acid (PEDOT:PSS) films. The figures show that the films are composed ...of grains with diameters in the range of about 50 nm. Energy dispersive X‐ray spectroscopy analysis reveals that individual grains have a PEDOT‐rich core and a PSS‐rich shell with a thickness of about 5–10 nm. Atomic force microscopy (AFM) is then used to analyze the topography of fracture surfaces of ruptured PEDOT:PSS tensile specimens. These AFM scans also show that the films are composed of grains dispersed in a matrix. The investigations presented herein yield a picture of PEDOT:PSS morphology with unprecedented clarity.
Electron microscopy studies are used to explore the morphology of thin poly(3,4‐ethylenedioxythiophene) and polystyrene sulfonate acid (PEDOT:PSS) films. The studies reveal the granular structure of the films. Energy dispersive X‐ray analysis and atomic force microscopy scans then show that the films are composed of grains with a PEDOT‐rich core dispersed in a PSS‐rich matrix.
Modern nanoelectronics has advanced to a point at which it is impossible to image entire devices and their interconnections non-destructively because of their small feature sizes and the complex ...three-dimensional structures resulting from their integration on a chip. This metrology gap implies a lack of direct feedback between design and manufacturing processes, and hampers quality control during production, shipment and use. Here we demonstrate that X-ray ptychography-a high-resolution coherent diffractive imaging technique-can create three-dimensional images of integrated circuits of known and unknown designs with a lateral resolution in all directions down to 14.6 nanometres. We obtained detailed device geometries and corresponding elemental maps, and show how the devices are integrated with each other to form the chip. Our experiments represent a major advance in chip inspection and reverse engineering over the traditional destructive electron microscopy and ion milling techniques. Foreseeable developments in X-ray sources, optics and detectors, as well as adoption of an instrument geometry optimized for planar rather than cylindrical samples, could lead to a thousand-fold increase in efficiency, with concomitant reductions in scan times and voxel sizes.
The analysis of ultralow input samples or even individual cells is essential to answering a multitude of biomedical questions, but current proteomic workflows are limited in their sensitivity and ...reproducibility. Here, we report a comprehensive workflow that includes improved strategies for all steps, from cell lysis to data analysis. Thanks to convenient-to-handle 1 μL sample volume and standardized 384-well plates, the workflow is easy for even novice users to implement. At the same time, it can be performed semi-automatized using CellenONE, which allows for the highest reproducibility. To achieve high throughput, ultrashort gradient lengths down to 5 min were tested using advanced μ-pillar columns. Data-dependent acquisition (DDA), wide-window acquisition (WWA), data-independent acquisition (DIA), and commonly used advanced data analysis algorithms were benchmarked. Using DDA, 1790 proteins covering a dynamic range of four orders of magnitude were identified in a single cell. Using DIA, proteome coverage increased to more than 2200 proteins identified from single-cell level input in a 20 min active gradient. The workflow enabled differentiation of two cell lines, demonstrating its suitability to cellular heterogeneity determination.
Asymmetric separators with polysulfide barrier properties consisting of porous polypropylene grafted with styrenesulfonate (PP-g-PLiSS) were characterized in lithium–sulfur cells to assess their ...practical applicability. Galvanostatic cycling at different C-rates with and without an electrolyte additive and cyclic voltammetry were used to probe the electrochemical performance of the cells with the PP-g-PLiSS separators and to compare it with the performance of the cells utilizing state-of-the-art separator, Celgard 2400. Overall, it was found that regardless of the applied cycling rate, the use of the grafted separators greatly enhances the Coulombic efficiency of the cell. An appropriate Li-exchange-site (−SO3 –) concentration at and near the surface of the separator was found to be essential to effectively suppress the polysulfide shuttle without sacrificing the Li-ion mobility through the separator and to improve the practical specific charge of the cell.
Triggering or enhancing antitumor activity of tumor-associated macrophages is an attractive strategy for cancer treatment. We have previously shown that the cytokine interferon-γ (IFN-γ), a type II ...IFN, could synergize with toll-like receptor (TLR) agonists for induction of antitumor M1 macrophages. However, the toxicity of IFN-γ limits its clinical use. Here, we investigated whether the less toxic type I IFNs, IFN-α, and IFN-β, could potentially replace IFN-γ for induction of antitumor M1 macrophages. We measured
the ability of type I and II IFNs to synergize with TLR agonists for transcription of inducible nitric oxide synthase (iNOS) mRNA and secretion of nitric oxide (NO) by mouse bone marrow-derived macrophages (BMDMs). An
growth inhibition assay was used to measure both cytotoxic and cytostatic activity of activated macrophages against Lewis lung carcinoma (LLC) cancer cells. We found that both type I and II IFNs could synergize with TLR agonists in inducing macrophage-mediated inhibition of cancer cell growth, which was dependent on NO. The ability of high dose lipopolysaccharide (LPS) to induce tumoricidal activity in macrophages in the absence of IFN-γ was shown to depend on induction of autocrine type I IFNs. Antitumor M1 macrophages could also be generated in the absence of IFN-γ by a combination of two TLR ligands when using the TLR3 agonist poly(I:C) which induces autocrine type I IFNs. Finally, we show that encapsulation of poly(I:C) into nanoparticles improved its potency to induce M1 macrophages up to 100-fold. This study reveals the potential of type I IFNs for activation of antitumor macrophages and indicates new avenues for cancer immunotherapy based on type I IFN signaling, including combination of TLR agonists.
The rapidly increasing production of engineered nanoparticles has created a demand for particle removal from industrial and communal wastewater streams. Efficient removal is particularly important in ...view of increasing long-term persistence and evidence for considerable ecotoxicity of specific nanoparticles. The present work investigates the use of a model wastewater treatment plant for removal of oxide nanoparticles. While a majority of the nanoparticles could be captured through adhesion to clearing sludge, a significant fraction of the engineered nanoparticles escaped the wastewater plant’s clearing system, and up to 6 wt % of the model compound cerium oxide was found in the exit stream of the model plant. Our study demonstrates a significant influence of surface charge and the addition of dispersion stabilizing surfactants as routinely used in the preparation of nanoparticle derived products. A detailed investigation on the agglomeration of oxide nanoparticles in wastewater streams revealed a high stabilization of the particles against clearance (adsorption on the bacteria from the sludge). This unexpected finding suggests a need to investigate nanoparticle clearance in more detail and demonstrates the complex interactions between dissolved species and the nanoparticles within the continuously changing environment of the clearing sludge.
We conducted a severe acute respiratory syndrome coronavirus 2 antibody seroprevalence study among >2,000 domestic cats from 4 countries during the first coronavirus disease wave in Europe. We found ...4.4% seroprevalence using a virus neutralization test and 4.3% using a receptor-binding domain ELISA, demonstrating probable human-to-cat transmission.
Chemists of all fields currently publish about 50 000 crystal structures per year, the vast majority of which are X‐ray structures. We determined two molecular structures by employing electron rather ...than X‐ray diffraction. For this purpose, an EIGER hybrid pixel detector was fitted to a transmission electron microscope, yielding an electron diffractometer. The structure of a new methylene blue derivative was determined at 0.9 Å resolution from a crystal smaller than 1×2 μm2. Several thousand active pharmaceutical ingredients (APIs) are only available as submicrocrystalline powders. To illustrate the potential of electron crystallography for the pharmaceutical industry, we also determined the structure of an API from its pill. We demonstrate that electron crystallography complements X‐ray crystallography and is the technique of choice for all unsolved cases in which submicrometer‐sized crystals were the limiting factor.
Electrons instead of X‐rays: An electron diffractometer was tailored and employed for de novo structure determination from submicrometer‐sized crystals. A new methylene blue derivative was analysed together with a microcrystalline extract of an active pharmaceutical ingredient from a pill. The results obtained on submicrometer‐sized samples complement X‐ray crystallography.
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