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The binding of molecules to the surface of nanoparticles (NPs) for the use as ligands to manipulate the catalytic properties of NPs is an emerging research area. Various studies with interesting results have been reported in the past few years, but it seems not clear how these findings could be merged into some kind of unified picture, describing the mechanism of action of ligands in heterogeneous catalysis. The aim of this article is to summarize some of the recent achievements in this field with focus on discussing these results using concepts from heterogeneous and homogeneous catalysis. By this it is attempted to separate the influence of ligands into (i) changing the surface properties and (ii) acting as a function above or perpendicular to the surface. The first aspect can be rationalized by the knowledge from bimetallic catalysis. In contrast, the second proposes the relevance of ligand–reactant interactions, as known from homogeneous catalysis, in order to manipulate adsorption, activation, and conversion of reactants. As the application of ligands in heterogeneous catalysis is still a young research field and the full potential of the approach still unknown, this article does not claim to give a complete summery of all results gained within this field. Instead, the author aims to present a picture that may give some guidance for future studies in this area, based on established knowledge from homo- and heterogeneous catalysis.

Since the first shedder test was formulated almost 20 years ago, a plethora of different test strategies has emerged. The amount of data generated so far is considerable. However, because of the limited reproducibility of its results, the reliability of the shedder concept is frequently questioned. This study provides a literature overview of applied shedder tests that capture the diversity of the concept. It is pointed out to what extent different classification criteria, workflows, and trace evaluation can impair the classification outcome. The robustness of shedder status was assessed by applying a promising approach established by Fonneløp et al. (Forensic Sci Int Genet 29:48–60, 21). Data provide similar results to those in recent studies but also ambiguous shedder classifications. The applied shedder test was adapted based on our own as well as the reviewed data. With novel classification parameters, promising results were achieved. This study reveals uncertainties and inconsistencies of the shedder concept. Recommendations for harmonization and transparency are proposed. Implementation of the recommendations may result in an increased impact on casework and transfer studies, including activity-level assessments. Furthermore, this study shows that moisturizers affect participants’ shedder status as well as DNA transfer. The impact appears to remain relevant even 60 min post ointment application but depends greatly on the type of moisturizer applied.

Cellular entry of the hepatitis B and D viruses (HBV/HDV) requires binding of the viral surface polypeptide preS1 to the hepatobiliary transporter Na + -taurocholate co-transporting polypeptide (NTCP). This interaction can be blocked by bulevirtide (BLV, formerly Myrcludex B), a preS1 derivative and approved drug for treating HDV infection. Here, to elucidate the basis of this inhibitory function, we determined a cryo-EM structure of BLV-bound human NTCP. BLV forms two domains, a plug lodged in the bile salt transport tunnel of NTCP and a string that covers the receptor’s extracellular surface. The N-terminally attached myristoyl group of BLV interacts with the lipid-exposed surface of NTCP. Our structure reveals how BLV inhibits bile salt transport, rationalizes NTCP mutations that decrease the risk of HBV/HDV infection, and provides a basis for understanding the host specificity of HBV/HDV. Our results provide opportunities for structure-guided development of inhibitors that target HBV/HDV docking to NTCP. Hepatitis B and D viruses require docking to the NTCP receptor protein for cell entry, an interaction that can be blocked by the drug bulevirtide. Here the authors use cryo-EM to reveal the structural basis of bulevirtide activity.

The diminished surface-area-normalized catalytic activity of highly dispersed Pt nanoparticles compared with bulk Pt is particularly intricate, and not yet understood. Here we report on the oxygen reduction reaction (ORR) activity of well-defined, size-selected Pt nanoclusters; a unique approach that allows precise control of both the cluster size and coverage, independently. Our investigations reveal that size-selected Pt nanoclusters can reach extraordinarily high ORR activities, especially in terms of mass-normalized activity, if deposited at high coverage on a glassy carbon substrate. It is observed that the Pt cluster coverage, and hence the interparticle distance, decisively influence the observed catalytic activity and that closely packed assemblies of Pt clusters approach the surface activity of bulk Pt. Our results open up new strategies for the design of catalyst materials that circumvent the detrimental dispersion effect, and may eventually allow the full electrocatalytic potential of Pt nanoclusters to be realized. The catalytic activity of highly dispersed platinum nanoparticles is not yet well understood. Now, a unique approach that allows precise control of both the size and coverage of platinum nanoclusters reveals that particle proximity influences the oxygen reduction rate of these size-selected clusters, especially in terms of mass normalized activity.

PurposeIn this paper, we describe six cases, where patients were falsely treated with pre-filled ropivacaine solution instead of medical saline solution for postoperative settings. Two of the patients died because of fatal concentrations of ropivacaine in blood, four survived with no further physical injury, and two of them showed typical intoxication symptoms. The collected blood and urine samples of the deceased, as well as the surviving patients, were analyzed in laboratory routine screening.MethodsRopivacaine and its main metabolite 3-OH-ropivacaine were analyzed by gas chromatography–mass spectrometry.ResultsAll of the six cases showed positive blood results of ropivacaine. Due to the poorly secured sample material of the survived patients at hospital, the quantitative examination of 3-OH-ropivacaine could not be carried out. In one fatal case, there were ropivacaine and 3-OH-ropivacaine traceable in urine. In all cases, metamizole was found in blood and traces of piritramide in urine. The amount of metamizole was within the upper limits of therapeutical treatment values. Patients with lower blood concentrations of ropivacaine showed more physical symptoms as compared to those with higher concentrations of active substances.ConclusionsIn the context of symptom development and intoxication, the speed of injection was a very important factor to cause fatal ropivacaine cases. To our knowledge, these are the first reported cases of fatal intoxication with ropivacaine.

This paper presents a thermoelectric gas microsensor with improved stability where platinum nanoparticles linked by bifunctional ligands are used as a catalyst. The sensor design provides a homogeneous temperature field over the membrane, an important factor for the long-term stability of the catalyst. A comprehensive study of heat transfer from the chip is performed to evaluate the convection heat loss coefficient and to understand its effect on the homogeneity of the temperature field in a real-time situation. The effect of highly heat-conductive thermopiles is also analyzed by comparing the temperature distribution and power consumption with a thermoresistive sensor of the same dimensions and materials. Despite the thermopiles, the thermoelectric sensor gives better temperature homogeneity and consumes 23% less power than the thermoresistive sensor for 90 °C average temperature on the membrane. A comparative stability analysis among ligand-linked nanoparticles with 5 different ligands and unprotected nanoparticles was done through 3 consecutive 24 h tests under 1.5% continuous hydrogen gas flow. The sensors give very stable output, almost no degradation, through 72 h (3 × 24 h) tests for 3 different ligand-linked nanoparticles. The sensor design provides superb stability to the catalyst: Even catalysts of unprotected nanoparticles withstood more than 24 h and the sensor signal degradation is only 20%.

Background The anti‐coronavirus disease 2019 (COVID‐19) vaccines are of paramount importance in the fight against the COVID‐19 pandemic. Both viral vector‐ and nucleic acid‐based vaccines are known to effectively induce protection against the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus by generating high antibody titers and effective T‐cell responses to the spike protein they encode. Although these vaccines are being applied worldwide and have been extensively investigated, the immunomorphological events at the vaccination site with respect to SARS‐CoV‐2 spike protein expression have not yet been described. Methods We had the opportunity to examine the deltoid muscles of three men who died shortly after vaccination for unrelated reasons. We examined the vaccination sites histologically and immunohistochemically with various antibodies. Furthermore we incubated two different cell lines with one vaccine and examined the expression of the spike protein. Results The vaccination sites show a dense lymphohistiocytic interstitial infiltrate which surrounds the small vessels and extends into the perimysium. The spike protein is expressed by histiocytic cells with a dendritic shape that are CD68‐positive and CD207‐negative, fibrocytes, and very rare S100‐positive cells. Interestingly, the skeletal muscle, being constitutively human leukocyte antigen (HLA)‐A,B,C‐negative, is induced at different levels in each specimen. In a cell culture experiment, we confirmed the ability of fibroblasts and interdigitating dendritic sarcoma cells to express spike protein in vitro after incubation with the Comirnaty vaccine. Conclusions Histiocytic cells and fibrocytes are the heralds of spike protein synthesis at the vaccination site. The underlying cause of this apparent cell specifity is unknown. This needs to be investigated in future experiments, for example in an animal model. Investigation of the morphological changes at the anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination site reveals an inflammatory infiltrate. We provide a characterization of this infiltrate by immunohistochemistry and demonstrate the expression of the spike protein.

Na+/taurocholate cotransporting polypeptide (NTCP, gene symbol SLC10A1) is a hepatic bile acid uptake carrier participating in the enterohepatic circulation of bile acids. Apart from its transporter function, NTCP acts as the high-affinity liver-specific receptor for the hepatitis B virus (HBV), which attaches via its preS1-peptide domain of the large surface protein to NTCP, subsequently leading to endocytosis of the virus/NTCP-receptor complex. Although the process of NTCP-dependent HBV infection of hepatocytes has received much attention over the last decade, the precise molecular sites of the virus/NTCP interaction have not been fully identified. Inspection of the primary protein sequence of human NTCP revealed 139YIYSRGIY146 as a highly conserved tyrosine-rich motif. To study the role of Y139, Y141 and Y146 amino acids in NTCP biology, the aforementioned residues were substituted with alanine, phenylalanine or glutamate (mimicking phosphorylation) using site-directed mutagenesis. Similar to wt NTCP, the Y139A, Y141A, Y146A, Y141F, Y146F, and Y146E mutants were expressed at the plasma membrane of HEK293 cells and exhibited intact bile acid transport function. Y146A, Y146E, and Y146F demonstrated transport kinetics comparable to wild-type NTCP with Km values of 57.3–112.4 µM and Vmax values of 6683–7579 pmol/mg protein/min. Only Y141E was transport deficient, most likely due to an intracellular accumulation of the mutant protein. Most importantly, Y146A and Y146E mutation completely abrogated binding of the viral preS1-peptide to NTCP, while the Y146F mutant of NTCP showed some residual binding competence for preS1. Consequently, the NTCP mutants Y146A and Y146E, when expressed in HepG2 hepatoma cells, showed complete loss of susceptibility for in vitro HBV infection. In conclusion, tyrosine 146, and to some extent tyrosine 141, both belonging to the tyrosine-rich motif 139YIYSRGIY146 of human NTCP, are newly identified amino acid residues that play an essential role in the interaction of HBV with its receptor NTCP and, thus, in the process of virus entry into hepatocytes.

Conducted Electrical Weapons (CEWs) are being used as the preferred non-lethal force option for police and special forces worldwide. This new technology challenges an exposed opponent similarly to the way they would be challenged by physical exercise combined with emotional stress. While adrenergic and metabolic effects have been meta-analyzed and reviewed, there has been no systematic review of the effects of CEWs on skeletal and cardiac muscle. A systematic and careful search of the MedLine database was performed to find publications describing pathophysiological cardiac and skeletal muscle effects of CEWs. For skeletal muscle effects, we analyzed all publications providing changes in creatine kinase, myoglobin and potassium. For cardiac effects, we analyzed reported troponin changes and arrhythmias related to short dart-to-heart-distances. Conducted electrical weapons satisfy all relevant electrical safety standards and there are, to date, no proven electrocution incidents caused by CEWs. A potential cardiovascular risk has been recognized by some of the experimental animal data. The effects on the heart appear to be limited to instances when there is a short dart-to-heart-distance. The effect on the skeletal muscle system appears to be negligible. A responsible use of a CEW on a healthy adult, within the guidelines proposed by the manufacturer, does not imply a significant health risk for that healthy adult.