Receptor‐Mediated Uptake of Boron‐Rich Neuropeptide Y Analogues for Boron Neutron Capture Therapy

Peptidic ligands selectively targeting distinct G protein‐coupled receptors that are highly expressed in tumor tissue represent a promising approach in drug delivery. Receptor‐preferring analogues of neuropeptide Y (NPY) bind and activate the human Y₁ receptor subtype (hY₁ receptor), which is found in 90 % of breast cancer tissue and in all breast‐cancer‐derived metastases. Herein, novel highly boron‐loaded Y₁‐receptor‐preferring peptide analogues are described as smart shuttle systems for carbaboranes as ¹⁰B‐containing moieties. Various positions in the peptide were screened for their susceptibility to carbaborane modification, and the most promising positions were chosen to create a multi‐carbaborane peptide containing 30 boron atoms per peptide with excellent activation and internalization patterns at the hY₁ receptor. Boron uptake studies by inductively coupled plasma mass spectrometry revealed successful uptake of the multi‐carbaborane peptide into hY₁‐receptor‐expressing cells, exceeding the required amount of 10⁹ boron atoms per cell. This result demonstrates that the NPY/hY receptor system can act as an effective transport system for boron‐containing moieties.     

Comparative Anti-Inflammatory Effects of Salix Cortex Extracts and Acetylsalicylic Acid in SARS-CoV-2 Peptide and LPS-Activated Human In Vitro Systems

The usefulness of anti-inflammatory drugs as an adjunct therapy to improve outcomes in COVID-19 patients is intensely discussed in this paper. Willow bark (Salix cortex) has been used for centuries to relieve pain, inflammation, and fever. Its main active ingredient, salicin, is metabolized in the human body into salicylic acid, the precursor of the commonly used pain drug acetylsalicylic acid (ASA). Here, we report on the in vitro anti-inflammatory efficacy of two methanolic Salix extracts, standardized to phenolic compounds, in comparison to ASA in the context of a SARS-CoV-2 peptide challenge. Using SARS-CoV-2 peptide/IL-1β- or LPS-activated human PBMCs and an inflammatory intestinal Caco-2/HT29-MTX co-culture, Salix extracts, and ASA concentration-dependently suppressed prostaglandin E2 (PGE₂), a principal mediator of inflammation. The inhibition of COX-2 enzyme activity, but not protein expression was observed for ASA and one Salix extract. In activated PBMCs, the suppression of relevant cytokines (i.e., IL-6, IL-1β, and IL-10) was seen for both Salix extracts. The anti-inflammatory capacity of Salix extracts was still retained after transepithelial passage and liver cell metabolism in an advanced co-culture model system consisting of intestinal Caco-2/HT29-MTX cells and differentiated hepatocyte-like HepaRG cells. Taken together, our in vitro data suggest that Salix extracts might present an additional anti-inflammatory treatment option in the context of SARS-CoV-2 peptides challenge; however, more confirmatory data are needed.     

Metformin Protects against Radiation-Induced Acute Effects by Limiting Senescence of Bronchial-Epithelial Cells

Radiation-induced damage to normal lung parenchyma remains a dose-limiting factor in thorax-associated radiotherapy (RT). Severe early and late complications with lungs can increase the risk of morbidity in cancer patients after RT. Herein, senescence of lung epithelial cells following RT-induced cellular stress, or more precisely the respective altered secretory profile, the senescence-associated secretory phenotype (SASP), was suggested as a central process for the initiation and progression of pneumonitis and pulmonary fibrosis. We previously reported that abrogation of certain aspects of the secretome of senescent lung cells, in particular, signaling inhibition of the SASP-factor Ccl2/Mcp1 mediated radioprotection especially by limiting endothelial dysfunction. Here, we investigated the therapeutic potential of a combined metformin treatment to protect normal lung tissue from RT-induced senescence and associated lung injury using a preclinical mouse model of radiation-induced pneumopathy. Metformin treatment efficiently limited RT-induced senescence and SASP expression levels, thereby limiting vascular dysfunctions, namely increased vascular permeability associated with increased extravasation of circulating immune and tumor cells early after irradiation (acute effects). Complementary in vitro studies using normal lung epithelial cell lines confirmed the senescence-limiting effect of metformin following RT finally resulting in radioprotection, while fostering RT-induced cellular stress of cultured malignant epithelial cells accounting for radiosensitization. The radioprotective action of metformin for normal lung tissue without simultaneous protection or preferable radiosensitization of tumor tissue might increase tumor control probabilities and survival because higher radiation doses could be used.     

Excitonic fano resonance in free-standing graphene

We investigate the role of electron-hole correlations in the absorption of free-standing monolayer and bilayer graphene using optical transmission spectroscopy from 1.5 to 5.5 eV. Line shape analysis demonstrates that the ultraviolet region is dominated by an asymmetric Fano resonance. We attribute this to an excitonic resonance that forms near the van Hove singularity at the saddle point of the band structure and couples to the Dirac continuum. The Fano model quantitatively describes the experimental data all the way down to the infrared. In contrast, the common noninteracting particle picture cannot describe our data. These results suggest a profound connection between the absorption properties and the topology of the graphene band structure.     

Colloidal quantum dots in all-dielectric high-Q pillar microcavities

We have fabricated all-dielectric high-Q optical pillar resonators with embedded colloidal CdSe/ZnS quantum dots or rods as light emitters by focused ion beam milling. Three-dimensional light confinement and distinct pillar microcavity modes are observed. Results from a waveguide model for the mode patterns and their spectral positions are in excellent agreement with the experimental data. Cavities with elliptical cross sections show higher quality factors in the short axis direction than do circular resonators of the same cross-sectional area.     

Exploring the Potential of Norbornene‐Modified Mannosamine Derivatives for Metabolic Glycoengineering

Metabolic glycoengineering (MGE) allows the introduction of unnaturally modified carbohydrates into cellular glycans and their visualization through bioorthogonal ligation. Alkenes, for example, have been used as reporters that can react through inverse‐electron‐demand Diels–Alder cycloaddition with tetrazines. Earlier, norbornenes were shown to be suitable dienophiles; however, they had not previously been applied for MGE. We synthesized two norbornene‐modified mannosamine derivatives that differ in the stereochemistry at the norbornene (exo/endo linkage). Kinetic investigations revealed that the exo derivative reacts more than twice as rapidly as the endo derivative. Through derivatization with 1,2‐diamino‐4,5‐methylenedioxybenzene (DMB) we confirmed that both derivatives are accepted by cells and incorporated after conversion to a sialic acid. In further MGE experiments the incorporated sugars were ligated to a fluorophore and visualized through confocal fluorescence microscopy and flow cytometry.     

Al/Ni : V/Ag metal stacks as rear‐side metallization for crystalline silicon solar cells

Rear sides of crystalline silicon solar cells are usually covered with aluminum on which it is difficult to solder. To ease soldering, we present a durability study for a Ni : V/Ag stack on evaporated Al as rear‐side metallization. We adapt this cost‐effective metallization stack from the microelectronic industry and investigate it as metallization for silicon solar cells. Here, a long‐term stability of the metallization and of the solder joint must be guaranteed for 25 years and is therefore evaluated in detail by thermal aging experiments. During this experiment, the mechanical stability of the solder joints is measured. The chemical stability and the intermetallic compound (IMC) growth within the solder joints are examined by secondary electron microscopy, backscattered electron imaging, and energy dispersive X‐ray analysis. Experiments with either a Sn–Ag‐coated copper tab or pure Sn–Ag solder show two different sorts of IMCs at the Ni : V/Solder interface. With the copper tab, a Cu–Ni–Sn compound, presumably (Cu_{1 ‐ x}Ni_x)₆Sn₅, grows at the Ni/solder interface, whereas in case of a pure Sn–Ag solder, a Ni–Sn compound grows, which is likely to be Ni₃Sn₄. Analysis of the reaction kinetics leads to activation energies of 77 and 42 kJ/mol, respectively, for a diffusion‐controlled IMC growth. By using temperature histograms of PV modules in the field, the necessary minimum Ni : V layer thickness is estimated: without a copper tab up to 1.6 µm Ni and with a copper tab less than 0.2 µm may be consumed by IMC formation during 25 years of lifetime. Copyright © 2012 John Wiley & Sons, Ltd.     

Determination of falcarinol in carrot (Daucus carota L.) genotypes using liquid chromatography/mass spectrometry

A new analytical method for the determination of falcarinol [(Z)-heptadeca-1,9-diene-4,6-diyn-3-ol] in carrot root samples has been developed and validated. The method consists of accelerated solvent extraction (ASE) of lyophilised carrot root samples with ethyl acetate and LC–MS analysis of the extracts. Falcarinol was determined by extracting the main ion species generated in the ESI positive mode, m/z 268 [M+H–H₂O+MeCN]⁺, from the full MS chromatogram. Quantitation was performed using a falcarinol calibration curve (correlation coefficient 0.9975) as an external standard and pelargonic acid vanillylamide as an internal standard. The method showed good precision with interday and intraday variation of less than 4% and high recovery (average recovery rate 97.9%). LOD (S/N = 3) and LOQ (S/N = 10) were 2.5 and 7 ng, respectively. Using this method, 27 different carrot genotypes grown and harvested under the same conditions were analyzed, and falcarinol contents ranging from 0.70 to 4.06 mg/100 g fresh weight were determined.