SARS-CoV-2 triggers complement activation through interactions with heparan sulfate

The complement system has been heavily implicated in severe COVID-19 with clinical studies revealing widespread gene induction, deposition, and activation. However, the mechanism by which complement is activated in this disease remains incompletely understood. Herein we examined the relationship between SARS-CoV-2 and complement by inoculating the virus in lepirudin-anticoagulated human blood. This caused progressive C5a production after 30 minutes and 24 hours, which was blocked entirely by inhibitors for factor B, C3, C5, and heparan sulfate. However, this phenomenon could not be replicated in cell-free plasma, highlighting the requirement for cell surface deposition of complement and interactions with heparan sulfate. Additional functional analysis revealed that complement-dependent granulocyte and monocyte activation was delayed. Indeed, C5aR1 internalisation and CD11b upregulation on these cells only occurred after 24 hours. Thus, SARS-CoV-2 is a non-canonical complement activator that triggers the alternative pathway through interactions with heparan sulfate.

Decoupling of dust cloud and embedding plasma for high electron depletion in nanodusty plasmas

In recent years nanoparticles (nps) have become key technological products, e.g. as coatings with tunable optical gap in third generation solar cells, as nanocrystals for photonic applications, and as pharmaceutical nanocarriers. In particle sources, that use reactive, nanodusty plasmas, a high dust density changes the properties of the dusty plasma compared to a dust free plasma considerably, as the electron depletion leads to a reduced number of free electrons. This is called the Havnes effect and was central for the understanding of the famous spokes in Saturns rings. We see here, that it is also important for technological applications. Using self excited dust density waves (DDW) as a diagnostic tool, it is possible for the first time, to completely characterize an argon discharge with embedded amorphous hydrocarbon nps of different size and density. The results show, that electron depletion governs the charge of dust grains, while the size of the particles has only a weak influence. The ion density and electric potential profile are almost independent of both, dust size as well as dust density. This suggests, that the rf generated plasma and the dust cloud coexist and coupling of both is weak.

Quantification and Phenotypic Characterization of Extracellular Vesicles from Patients with Acute Myeloid and B-Cell Lymphoblastic Leukemia

Extracellular vesicles (EVs) act in cell-to-cell communication, delivering cargo from donor to recipient cells and modulating their physiological condition. EVs secreted by leukemic blasts in patients with leukemia have been shown to influence the fate of recipient cells in the bone marrow microenvironment. Methods to quantify and to characterize them phenotypically are therefore urgently needed to study their functional role in leukemia development and to evaluate their potential as targets for therapy. We have used cryo-electron microscopy to study morphology and size of leukemic EVs, and nanoparticle tracking analysis and fluorescence triggering flow cytometry to quantify EVs in platelet-free plasma from a small cohort of leukemia patients and healthy blood donors. Additional studies with a capture bead-based assay allowed us to establish phenotypic signatures of leukemic EVs from 17 AML and 3 B-ALL patients by evaluating the expression of 37 surface antigens. In addition to tetraspanins and lineage-specific markers we found several adhesion molecules (CD29, and CD146) to be highly expressed by EVs from B-ALL and several leukemic stem cell antigens (CD44, CD105, CD133, and SSEA-4) to be expressed by EVs from AML patients. Further improvements in analytical methods to study EVs are needed before potentially using them as biomarkers for leukemia prognosis and follow-up.

The More, the Merrier…? Antipsychotic Polypharmacy Treatment Strategies in Schizophrenia From a Pharmacology Perspective

Antipsychotic polypharmacy/drug combination treatment (APP) is a remarkably common practice in the schizophrenia context, given the lack of general support in treatment Guidelines. There is also a vast literature on APP outcomes, but a paucity of high-quality evidence-based data to guide and optimize adequate use of APP. This seems particularly true regarding many pharmacology-based considerations involved in APP treatment strategies. This paper first briefly summarizes clinical literature related to the use of APP. Against this backdrop, the pharmacological target profile features are then described of frequently used antipsychotic agents, in relation to estimated free plasma exposure levels at clinically efficacious dosing. APP strategies based on the properties of these drugs are then scrutinized and gauged within the background literature framework. The anticipated usefulness of APP from the pharmacological standpoint is detailed regarding efficacy, adverse effect (AE)/tolerability, and safety perspective, including why, when, and how it may be used to its advantage. For the purpose, a number of theoretically beneficial combinations as well as instances with suboptimal—and even futile—APP approaches are exemplified and discussed from the rational pharmacodynamic and pharmacokinetic pros and cons point-of-view. In this exposé, particular attention is paid to the utility and features of 3rd Generation Antipsychotic dopamine (DA) D2-D3 agonists within an APP setting.

Comparison between Bosch and STiGer Processes for Deep Silicon Etching

The cryogenic process is well known to etch high aspect ratio features in silicon with smooth sidewalls. A time-multiplexed cryogenic process, called STiGer, was developed in 2006 and patented. Like the Bosch process, it consists in repeating cycles composed of an isotropic etching step followed by a passivation step. If the etching step is similar for both processes, the passivation step is a SiF4/O2 plasma that efficiently deposits a SiOxFy layer on the sidewalls only if the substrate is cooled at cryogenic temperature. In this paper, it is shown that the STiGer process can achieve profiles and performances equivalent to the Bosch process. However, since sidewall passivation is achieved with polymer free plasma chemistry, less frequent chamber cleaning is necessary, which contributes to increase the throughput.

Modulatory Effect of 4-(methylthio)butyl Isothiocyanate Isolated From Eruca Sativa Thell. on DMBA Induced Overexpression of Hypoxia and Glycolytic Pathway in Sprague-Dawley Female Rats

4-(methylthio)butyl isothiocyanate (4-MTBITC) is a hydrolytic product from the plant Eruca sativa Thell. In the present study, we explored the anti-cancer effect of 4-MTBITC against 7,12-dimethylbenz [a] anthracene (DMBA) induced breast cancer. Hypoxic conditions were developed using a single dose of 60 mg/kg DMBA. Hepatic and renal parameters were increased along with antioxidants in cancer-bearing rats which were lowered with the treatment of 4-MTBITC. Further, it inhibited the up-regulation of glycolytic enzymes caused by DMBA. The hypoxia pathway was evaluated using RT-PCR and it was found that the 40 mg/kg doses of 4-MTBITC statistically lowered the expression of HIF-1α. Akt/mTOR signaling pathway was one of the major pathways involved in 4-MTBITC-induced cell growth arrest by western blotting. Amino acid profiling serum-free plasma revealed the downregulation of specific amino acids required for vital components of fast-growing cancer cells. 4-MTBITC reduced the levels of serine, arginine, alanine, asparagines, and glutamic acid. Histological examination also showed neoplastic growth following DMBA doses. 4-MTBITC treated rats showed less infiltration and normal physiology. Our findings for the first time demonstrated the potential therapeutic significance of 4-MTBITC on modulation of glycolytic enzymes and hypoxia pathway in female rats.