Intramyocardial Inflammation after COVID-19 Vaccination: An Endomyocardial Biopsy-Proven Case Series

Myocarditis in response to COVID-19 vaccination has been reported since early 2021. In particular, young male individuals have been identified to exhibit an increased risk of myocardial inflammation following the administration of mRNA-based vaccines. Even though the first epidemiological analyses and numerous case reports investigated potential relationships, endomyocardial biopsy (EMB)-proven cases are limited. Here, we present a comprehensive histopathological analysis of EMBs from 15 patients with reduced ejection fraction (LVEF = 30 (14–39)%) and the clinical suspicion of myocarditis following vaccination with Comirnaty^® (Pfizer-BioNTech) (n = 11), Vaxzevria^® (AstraZenica) (n = 2) and Janssen^® (Johnson & Johnson) (n = 2). Immunohistochemical EMB analyses reveal myocardial inflammation in 14 of 15 patients, with the histopathological diagnosis of active myocarditis according the Dallas criteria (n = 2), severe giant cell myocarditis (n = 2) and inflammatory cardiomyopathy (n = 10). Importantly, infectious causes have been excluded in all patients. The SARS-CoV-2 spike protein has been detected sparsely on cardiomyocytes of nine patients, and differential analysis of inflammatory markers such as CD4⁺ and CD8⁺ T cells suggests that the inflammatory response triggered by the vaccine may be of autoimmunological origin. Although a definitive causal relationship between COVID-19 vaccination and the occurrence of myocardial inflammation cannot be demonstrated in this study, data suggest a temporal connection. The expression of SARS-CoV-2 spike protein within the heart and the dominance of CD4⁺ lymphocytic infiltrates indicate an autoimmunological response to the vaccination.     

Targeting CD10 on B-Cell Leukemia Using the Universal CAR T-Cell Platform (UniCAR)

Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), and the occurrence of side effects that could be severe in some cases. Therefore, it became clear that improved safety approaches, and targeting multiple antigens, should be considered to further improve CAR T-cell therapy for B-ALL. In this paper, we address both issues by investigating the use of CD10 as a therapeutic target for B-ALL with our switchable UniCAR system. The UniCAR platform is a modular platform that depends on the presence of two elements to function. These include UniCAR T-cells and the target modules (TMs), which cross-link the T-cells to their respective targets on tumor cells. The TMs function as keys that control the switchability of UniCAR T-cells. Here, we demonstrate that UniCAR T-cells, armed with anti-CD10 TM, can efficiently kill B-ALL cell lines, as well as patient-derived B-ALL blasts, thereby highlighting the exciting possibility for using CD10 as an emerging therapeutic target for B-cell malignancies.     

Metallchelate ungesättigter 1,2-Dithioäther

Metal Chelates of Unsaturated 1,2-Dithioethers The dialkyl- and diaralkyldithioethers of ethylenebisthiol (edt) and xylenedithiol form cationic 1:2 chelates with the d⁸-metal ions Ag^I and Cu^I, which have been isolated and characterized. Pd^II- and Pt^II-halides yield neutral mixed ligand complexes of the type Me (L L) X₂ (L L = dithioether, X = halogen). The dibenzyldithioether of edt is cleaved oxidatively by Cu^II and yields dibenzyldisulfide, Cu^I and an unidentified product.     

Model complexity reduction of chemical reaction networks using mixed-integer quadratic programming

The model complexity reduction problem of large chemical reaction networks under isobaric and isothermal conditions is considered. With a given detailed kinetic mechanism and measured data of the key species over a finite time horizon, the complexity reduction is formulated in the form of a mixed-integer quadratic optimization problem where the objective function is derived from the parametric sensitivity matrix. The proposed method sequentially eliminates reactions from the mechanism and simultaneously tunes the remaining parameters until the pre-specified tolerance limit in the species concentration space is reached. The computational efficiency and numerical stability of the optimization are improved by a pre-reduction step followed by suitable scaling and initial conditioning of the Hessian involved. The proposed complexity reduction method is illustrated using three well-known case studies taken from reaction kinetics literature.     

Processing issues related to the bi-dimensional ionic conductivity of BIMEVOX ceramics

Bismuth vanadate, Bi₄V₂O₁₁, and its doped variations, Bi₄(Co_0.15V_0.85)₂O₁₁, Bi₄(Cu_0.1V_0.9)₂O₁₁, and Bi₄(Cu_0.05Ti_0.05V_0.90)₂O₁₁ are investigated with respect to relative processability and total conductivity. In conventionally prepared (pressure-less sintered) ceramic disks, the single-substitution compounds show signs of exaggerated grain growth with significant c-axis preferred orientation. The doubly substituted Bi₄(Cu_0.05Ti_0.05V_0.90)₂O₁₁ is found to have the widest processing window, resulting in sintered monoliths with the highest relative density and no preferred orientation. It also shows the highest conductivity (7 × 10 ⁻² (Ωcm) ⁻¹) at 500 °C, as measured by impedance spectroscopy. Activation energies for conduction of the four compounds are reported and found to be comparable to earlier study. Hot forged samples of Bi₄(Cu_0.05Ti_0.05V_0.90)₂O₁₁ are prepared for the first time, with only moderate texturing achieved. We assert that the lack of texture in Bi₄(Cu_0.05Ti_0.05V_0.90)₂O₁₁ is responsible for the higher conductivity measured through the sample thickness when compared to Bi₄(Co_0.15V_0.85)₂O₁₁, Bi₄(Cu_0.1V_0.9)₂O₁₁ and other related compounds.     

The effect of heat treatment on the microfibrillar network of poly(p-phenylene benzobisthiazole)

Materials exhibiting exceptional mechanical properties can be fabricated from rigid polymers. In a spinning process, an oriented solution is solidified by the action of a nonsolvent, which induces crystallization of an oriented rigid polymer. Drying and heat treatment result in the final material having the desired properties. The effect of heat treatment on the morphology of poly(p-phenylene benzobisthiazole) (PBZT) films was studied by measurements of small-angle X-ray scattering (SAXS) and wide-angle X-ray diffraction (WAXD). Films were formed by coagulation in water. The wet films were dried with supercritical CO₂ to maintain an open network structure. Coagulation in water resulted in formation of microfibrils having diameter of ∼9 nm. Heat-treatment at 600°C caused significant coalescence of microfibrils. The crystallite size was increased by heat treatment from a value that is smaller than the microfibrillar diameter indicating defects in chain packing, to a value comparable to the microfibrillar diameter.     

TcdB of Clostridioides difficile Mediates RAS-Dependent Necrosis in Epithelial Cells

A Clostridioides difficile infection (CDI) is the most common nosocomial infection worldwide. The main virulence factors of pathogenic C. difficile are TcdA and TcdB, which inhibit small Rho-GTPases. The inhibition of small Rho-GTPases leads to the so-called cytopathic effect, a reorganization of the actin cytoskeleton, an impairment of the colon epithelium barrier function and inflammation. Additionally, TcdB induces a necrotic cell death termed pyknosis in vitro independently from its glucosyltransferases, which are characterized by chromatin condensation and ROS production. To understand the underlying mechanism of this pyknotic effect, we conducted a large-scale phosphoproteomic study. We included the analysis of alterations in the phosphoproteome after treatment with TcdA, which was investigated for the first time. TcdA exhibited no glucosyltransferase-independent necrotic effect and was, thus, a good control to elucidate the underlying mechanism of the glucosyltransferase-independent effect of TcdB. We found RAS to be a central upstream regulator of the glucosyltransferase-independent effect of TcdB. The inhibition of RAS led to a 68% reduction in necrosis. Further analysis revealed apolipoprotein C-III (APOC3) as a possible crucial factor of CDI-induced inflammation in vivo.     

Säurekatalysierte Umsetzungen von Aromaten mit Alkanen und Cycloalkanen. IX. Alkylierungen mit 2,2,4-Trimethylpentan (Isooctan)

Acid-catalyzed Reactions of Aromatic Hydrocarbons with Alkanes and Cycloalkanes. IX. Alkylations with 2,2,4-Trimethylpentane (Isooctane) The non-conventional alkylation of benzene, toluene, ethyl- and isopropylbenzene, fluoro- and chlorobenzene with 2,2,4-trimethylpentane in the presence of acid catalysts is described. The composition of the rather complex reaction mixtures is determined by gas-liquid chromatography and mass spectrometry, tert. butylarenes being the main products beside alkylsubstituted indanes and tetralines. Their formation is interpreted as a competition between fragmentation and isomerization of the alkylating agent. By use of trifluoromethanesulfonic acid or combinations of catalysts from HF or HSO₃F with variant metallic fluorides at lower temperatures the selectivity of the reaction may be partially raised.     

在机床研发中基于职能单位的产品开发理论与实践

通过调查得知,包括虚拟现实技术在机床制造中应用可能性的应用方法、策略和工具在产品开发中的现状.对调查结果进行了讨论,考虑到研究理论的可移植性和对企业内部实战的依赖性.讨论的结果为基础研究领域的命题"基于职能单位的产品开发"提供结论.