Ionizable lipids based on branched fatty acids - An explorative study on Langmuir monolayers.

Ionizable lipids are a class of pharmaceutical excipients with a main application in lipid nanoparticles for nucleic acid delivery. New ionizable lipids are needed to tune characteristics of lipid-based nucleic acid delivery systems, e.g.

Novel NKG2D-directed bispecific antibodies enhance antibody-mediated killing of malignant B cells by NK cells and T cells.

The activating receptor natural killer group 2, member D (NKG2D) represents an attractive target for immunotherapy as it exerts a crucial role in cancer immunosurveillance by regulating the activity of cytotoxic lymphocytes. In this study, a panel of novel NKG2D-specific single-chain fragments variable (scFv) were isolated from naïve human antibody gene libraries and fused to the fragment antigen binding (Fab) of rituximab to obtain [CD20×NKG2D] bibodies with the aim to recruit cytotoxic lymphocytes to lymphoma cells. All bispecific antibodies bound both antigens simultaneously.

Suggestion Timing Moderates the Effects of Prior Pain Experiences on Pain Perception.

Two common elements in patient care are reoccurring painful events (eg, blood draws) and verbal suggestions from others for lessened pain. Research shows that verbal suggestions for lower pain can decrease subsequent pain perception from novel noxious stimuli, but it is less clear how these suggestions and prior painful experiences combine to influence the perception of a reoccurring painful event. The presented experiment tested the hypothesis that the order of these 2 factors influence pain perception for a reoccurring painful event.

Differential Upregulation and Functional Activity of S1PR1 in Human Peripheral Blood Basophils of Atopic Patients.

Basophils are key effector cells in atopic diseases, and the signaling sphingolipid Sphigosine-1-phosphate (S1P) is emerging as an important mediator in these conditions. The possible interaction of S1P and basophils and the resulting biological effects have not yet been studied. We hypothesize that S1P influences the function of basophils in atopy and aim to elucidate the modes of interaction.

Lipoplex-Functionalized Thin-Film Surface Coating Based on Extracellular Matrix Components as Local Gene Delivery System to Control Osteogenic Stem Cell Differentiation.

A gene-activated surface coating is presented as a strategy to design smart biomaterials for bone tissue engineering. The thin-film coating is based on polyelectrolyte multilayers composed of collagen I and chondroitin sulfate, two main biopolymers of the bone extracellular matrix, which are fabricated by layer-by-layer assembly. For further functionalization, DNA/lipid-nanoparticles (lipoplexes) are incorporated into the multilayers.

Investigating 3R In Vivo Approaches for Bio-Distribution and Efficacy Evaluation of Nucleic Acid Nanocarriers: Studies on Peptide-Mimicking Ionizable Lipid.

Formulations based on ionizable amino-lipids have been put into focus as nucleic acid delivery systems. Recently, the in vitro efficacy of the lipid formulation OH4:DOPE has been explored. However, in vitro performance of nanomedicines cannot correctly predict in vivo efficacy, thereby considerably limiting pre-clinical translation.

Antibody bivalency improves antiviral efficacy by inhibiting virion release independently of Fc gamma receptors.

Across the animal kingdom, multivalency discriminates antibodies from all other immunoglobulin superfamily members. The evolutionary forces conserving multivalency above other structural hallmarks of antibodies remain, however, incompletely defined. Here, we engineer monovalent either Fc-competent or -deficient antibody formats to investigate mechanisms of protection of neutralizing antibodies (nAbs) and non-neutralizing antibodies (nnAbs) in virus-infected mice.

Anticoagulation Prior to COVID-19 Infection Has No Impact on 6 Months Mortality: A Propensity Score-Matched Cohort Study.

The coronavirus disease 2019 (COVID-19) shows high incidence of thromboembolic events in humans. In the present study, we aimed to evaluate if anticoagulation prior to COVID-19 infection may impact clinical profile, as well as mortality rate among patients hospitalized with COVID-19. The study was based on retrospective analysis of medical records of patients with laboratory confirmed SARS-CoV-2 infection.

The Disruptiveness of Itchiness from Psoriasis: A Qualitative Study of the Impact of a Single Symptom on Quality of Life.

Background: Pruritus is the most common symptom of psoriasis, with a significant impact on patient quality of life. In spite of this, the severity, persistence, and overall impact of itchiness has only been rarely formally assessed during standard psoriasis clinic visits. Objectives: We sought to understand the far-reaching impacts of itchiness on the lives of those with psoriasis and their families.

Pan-tropical Sentinel-2 cloud-free annual composite datasets.

Sentinel-2 MSI is one of the core missions of the Copernicus Earth Observation programme of the European Union. This mission shows great potential to map the regional high-resolution spatio-temporal dynamics of land use and land cover. In tropical regions, despite the high revisiting time of 5 days including both Sentinel-2A and 2B satellites, the frequent presence of clouds, cloud-shadows, haze and other atmospheric contaminants are precluding the visibility of the Earth surface up to several months.

Efficient Transfection of Large Plasmids Encoding HIV-1 into Human Cells-A High Potential Transfection System Based on a Peptide Mimicking Cationic Lipid.

One major disadvantage of nucleic acid delivery systems is the low transfection or transduction efficiency of large-sized plasmids into cells. In this communication, we demonstrate the efficient transfection of a 15.5 kb green fluorescent protein (GFP)-fused HIV-1 molecular clone with a nucleic acid delivery system prepared from the highly potent peptide-mimicking cationic lipid OH4 in a mixture with the phospholipid DOPE (co-lipid).

2 MW peak power generation in fluorine co-doped Yb fiber prepared by powder-sinter technology.

We report on the first, to the best of our knowledge, implementation of a fluorine co-doped large-mode-area REPUSIL fiber for high peak power amplification in an ultrashort-pulse master oscillator power amplifier. The core material of the investigated step-index fiber with high Yb-doping level, 52 µm core and high core-to-clad ratio of 1:4.2 was fabricated by means of the REPUSIL powder-sinter technology.

Contact-Triggered Lipofection from Multilayer Films Designed as Surfaces for in Situ Transfection Strategies in Tissue Engineering.

Biomaterials, which release active compounds after implantation, are an essential tool for targeted regenerative medicine. In this study, thin multilayer films loaded with lipid/DNA complexes (lipoplexes) were designed as surface coatings for in situ transfection applicable in tissue engineering and regenerative medicine. The film production and embedding of lipoplexes were based on the layer-by-layer (LbL) deposition technique.

A triple chain polycationic peptide-mimicking amphiphile - efficient DNA-transfer without co-lipids.

Non-viral gene delivery in its current form is largely dependent upon the ability of a delivery vehicle to protect its cargo in the extracellular environment and release it efficiently inside the target cell. Also a simple delivery system is required to simplify a GMP conform production if a marketing authorization is striven for. This work addresses these problems.

Nucleic acid carrier composed of a branched fatty acid lysine conjugate-Interaction studies with blood components.

For the development of gene therapeutics for systemic administration several hurdles have to be overcome. In this article we screen the branched fatty acid lysine conjugate T14diLys, a newly designed cationic lipid for lipofection, regarding this problem. The structure and particle size of lipoplexes, prepared with lipid formulations which are based on these lipid as nucleic acid complexing agent, are investigated in absence and presence of serum.

The Impact of Alkyl-Chain Purity on Lipid-Based Nucleic Acid Delivery Systems - Is the Utilization of Lipid Components with Technical Grade Justified?

The physicochemical properties and transfection efficacies of two samples of a cationic lipid have been investigated and compared in 2D (monolayers at the air/liquid interface) and 3D (aqueous bulk dispersions) model systems using different techniques. The samples differ only in their chain composition due to the purity of the oleylamine (chain precursor). Lipid 8 (using the oleylamine of technical grade for cost-efficient synthesis) shows lateral phase separation in the Langmuir layers.

A microfluidic co-cultivation platform to investigate microbial interactions at defined microenvironments.

Interspecies interactions inside microbial communities bear a tremendous diversity of complex chemical processes that are by far not understood. Even for simplified, often synthetic systems, the interactions between two microbes are barely revealed in detail. Here, we present a microfluidic co-cultivation platform for the analysis of growth and interactions inside microbial consortia with single-cell resolution.

Human carotid bodies as a therapeutic target: new insights from a clinician's perspective.

From the physiological point of view, carotid bodies are mainly responsible for the ventilatory response to hypoxia; however, they also take part in the regulation of sympathetic tone. According to preclinical data, these structures likely contribute to the development and progression of sympathetically mediated diseases. Moreover, carotid body deactivation in animal models improved blood pressure control in hypertension and reduced mortality in heart failure, along with reducing sympathetic activity.

The long periodicity phase (LPP) controversy part I: The influence of a natural-like ratio of the CER[EOS] analogue [EOS]-br in a CER[NP]/[AP] based stratum corneum modelling system: A neutron diffraction study.

This study used neutron diffraction to investigate a ceramide-[NP] C24/[AP] C24 /[EOS]-br C30/cholesterol/lignoceric acid (0.6: 0.3: 0.

Lysine-based amino-functionalized lipids for gene transfection: 3D phase behaviour and transfection performance.

Based on previous work, the influence of the chain composition on the physical-chemical properties of five new transfection lipids (TH10, TT10, OH10, OT10 and OO10) containing the same lysine-based head group has been investigated in aqueous dispersions. For this purpose, the chain composition has been gradually varied from saturated tetradecyl (T, C14:0) and hexadecyl (H, C16:0) chains to longer but unsaturated oleyl (O, C18:1) chains with double bonds in the cis configuration. In this work, the lipid dispersions have been investigated in the absence and presence of the helper lipid DOPE and calf thymus DNA by small-angle and wide-angle X-ray scattering (SAXS/WAXS) supplemented by differential scanning calorimetry (DSC), attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) and Fourier-transform Raman spectroscopy (FTRS).

Overcoming the polycation dilemma - Explorative studies to characterise the efficiency and biocompatibility of newly designed lipofection reagents.

In this explorative study of the novel cationic lipid OO4 in two different formulations the complex formation with DNA, the biopharmaceutical stability of the lipid/DNA complexes in physiological media, and the transfection efficiency were analysed. We investigated liposomes composed of two binary mixtures of OO4 with either DOPE or DPPE as co-lipids in the molar ratio of 1:3. These formulations were compared with regard to their ability to bind the DNA using gel retardation electrophoresis, ethidium bromide exclusion and zeta potential measurements.