Synthesis and in vitro Study of Artemisinin/Synthetic Peroxide-Based Hybrid Compounds against SARS-CoV-2 and Cancer

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause life-threatening diseases in millions of people worldwide, in particular, in patients with cancer, and there is an urgent need for antiviral agents against this infection. While in vitro activities of artemisinins against SARS-CoV-2 and cancer have recently been demonstrated, no study of artemisinin and/or synthetic peroxide-based hybrid compounds active against both cancer and SARS-CoV-2 has been reported yet. However, the hybrid drug's properties (e. g., activity and/or selectivity) can be improved compared to its parent compounds and effective new agents can be obtained by modification/hybridization of existing drugs or bioactive natural products. In this study, a series of new artesunic acid and synthetic peroxide based new hybrids were synthesized and analyzed in vitro for the first time for their inhibitory activity against SARS-CoV-2 and leukemia cell lines. Several artesunic acid-derived hybrids exerted a similar or stronger potency against K562 leukemia cells (81–83 % inhibition values) than the reference drug doxorubicin (78 % inhibition value) and they were also more efficient than their parent compounds artesunic acid (49.2 % inhibition value) and quinoline derivative (5.5 % inhibition value). Interestingly, the same artesunic acid-quinoline hybrids also show inhibitory activity against SARS-CoV-2 in vitro (EC₅₀ 13–19 μm ) and no cytotoxic effects on Vero E6 cells (CC₅₀ up to 110 μM). These results provide a valuable basis for design of further artemisinin-derived hybrids to treat both cancer and SARS-CoV-2 infections.     

Novel allene oxide synthase products formed via Favorskii-type rearrangement: mechanistic implications for 12-oxo-10,15-phytodienoic acid biosynthesis

The allene oxide synthase (AOS) pathway is widespread in plants. Its products, such as cyclopentenone 12-oxo-10,15-phytodienoic acid (12-oxo-PDA) and related jasmonates, play important biological roles in plants. We found that 12-oxo-PDA in some plant tissues co-occur with an unknown minor oxylipin 1. In vitro incubations of AOSs with α-linolenic acid 13(S)-hydroperoxide reliably afforded 1 along with 12-oxo-PDA and α-ketol. A similar oxylipin 3 was formed during the AOS conversions of γ-linolenic acid 9(S)-hydroperoxide. Linoleic acid hydroperoxides formed neither products similar to 1 and 3 nor cyclopentenones. Oxylipins 1 and 3 were purified and identified as the products of Favorskii-type rearrangement, (2'Z,4Z)-2-(2'-pentenyl)-4-tridecene-1,13-dioic acid and (2'Z,4Z)-2-(2'-octenyl)-4-decene-1,10-dioic acid, respectively. Detection of Favorskii products 1 and 3 demonstrates that cyclopropanones are short-lived AOS products along with allene oxides. The observed parallels between the Favorskii product 1 and 12-oxo-PDA formation suggests that cyclopropanone is either a byproduct or a precursor of 12-oxo-PDA.     

The importance of ‘process’ in Rethinking Project Management: The story of a UK Government-funded research network

This paper tells the story of a UK Government-funded research network called Rethinking Project Management, funded by the Engineering and Physical Sciences Research Council between 2004 and 2006. The story is significant because of the considerable attention given to the process of the Network, both the inquiry process of ‘rethinking’ project management, and the broader social process in which the rethinking activity was carried out. In telling this story, the lead organisers explain how the inquiry process was organised as a learning system to enable the Network to ‘learn’ its way to relevant directions for future research, and secondly, how the broader social process was organised and facilitated to create a context for effective interaction between the people involved. A significant challenge in managing the research programme was how to engage the participants in purposeful inquiry, which would serve not only the primary aims of the Network, but would also yield new and interesting insights for the people involved. This paper seeks to explain how the lead organisers addressed this challenge, through a detailed and reflective discussion of how the research programme was organised and facilitated to achieve the Network’s primary aims. In summary, the principal aim in telling this story is to highlight the importance of process in collaborative research activity involving academics and practitioners, in order that other researchers might draw on the experience of this Network.     

Test of the FDTD accuracy in the analysis of the scattering resonances associated with high-Q whispering-gallery modes of a circular cylinder

Our objective is the assessment of the accuracy of a conventional finite-difference time-domain (FDTD) code in the computation of the near- and far-field scattering characteristics of a circular dielectric cylinder. We excite the cylinder with an electric or magnetic line current and demonstrate the failure of the two-dimensional FDTD algorithm to accurately characterize the emission rate and the field patterns near high-Q whispering-gallery-mode resonances. This is proven by comparison with the exact series solutions. The computational errors in the emission rate are then studied at the resonances still detectable with FDTD, i.e., having Q-factors up to 10(3).     

Photonic-plasmonic scattering resonances in deterministic aperiodic structures

In this paper, we combine experimental dark-field scattering spectroscopy and accurate electrodynamics calculations to investigate the scattering properties of two-dimensional plasmonic lattices based on the concept of aperiodic order. In particular, by discussing visible light scattering from periodic, Fibonacci, Thue-Morse and Rudin-Shapiro lattices fabricated by electron-beam lithography on transparent quartz substrates, we demonstrate that deterministic aperiodic Au nanoparticle arrays give rise to broad plasmonic resonances spanning the entire visible spectrum. In addition, we show that far-field diffractive coupling is responsible for the formation of characteristic photonic-plasmonic scattering modes in aperiodic arrays of metal nanoparticles. Accurate scattering simulations based on the generalized Mie theory approach support our experimental results. The possibility of engineering complex metal nanoparticle arrays with distinctive plasmonic resonances extending across the entire visible spectrum can have a significant impact on the design and fabrication of novel nanodevices based on broadband plasmonic enhancement.     

Combinatorial approach to the preparation and characterization of catalysts for biomass steam reforming into syngas

A number of catalysts based on Al₂O₃ loaded with doped Ce-Zr mixed oxides and different active components (Cu, Cu-Ni, Ru, Pt, etc.) were synthesized via standard wet impregnation method using the robotic workstation. Ethanol (EtOH) was taken as a model compound of bio-oil and steam reforming of ethanol (ESR)—as a model reaction. Activity screening experiments performed at 600–700 °C in 0.5 vol.% C₂H₅OH + 2.5 vol.% H₂O + 97 vol.% He mixture revealed that the most effective catalyst composition is Ru/Ce_0.4Zr_0.4Sm_0.2/Al₂O₃. Catalytic activity investigations at high reagent concentrations (10 vol.% C₂H₅OH + 40 vol.% H₂O + 50 vol.% N₂) at 650–800 °C confirmed this fact, revealing also that at high temperatures the activity of Cu-Ni catalysts is comparable with that of Ru-containing catalyst.     

Biogenic amine and microbiological profile of Serbian dry fermented sausages of artisanal and industrial origin and associated health risk

ABSTRACT

From the public health point of view, safety of dry fermented sausages is of concern due to possible presence of biogenic amines and some other food hazards. Taking into consideration that biogenic amines are chemical indicators of microbiological contamination, industrial and artisanal dry fermented sausages produced in Serbia were subjected to the microbiological and biogenic amine profiling. Microorganisms identified by MALDI-TOF MS included Cronobacter sakazakii and Listeria innocua, whereas the food pathogens were not detected. Biogenic amine content, determined by HPLC method in the range from 37.3 to 1186 mg/kg, was characterised as very low to low in 40% of the samples, moderate in 38%, high in 14% and very high in 8%. Risk assessment revealed that consumption of dry fermented sausages could cause histamine and tyramine intake up to 11.9% and 3.4% of threshold dose for healthy population, respectively. Adverse health effects would be rather unlikely for general population.     

Loss of swiss cheese in Neurons Contributes to Neurodegeneration with Mitochondria Abnormalities,Reactive Oxygen Species Acceleration and Accumulation of Lipid Droplets in Drosophila Brain

Various neurodegenerative disorders are associated with human NTE/PNPLA6 dysfunction. Mechanisms of neuropathogenesis in these diseases are far from clearly elucidated. Hereditary spastic paraplegia belongs to a type of neurodegeneration associated with NTE/PNLPLA6 and is implicated in neuron death. In this study, we used Drosophila melanogaster to investigate the consequences of neuronal knockdown of swiss cheese (sws)—the evolutionarily conserved ortholog of human NTE/PNPLA6—in vivo. Adult flies with the knockdown show longevity decline, locomotor and memory deficits, severe neurodegeneration progression in the brain, reactive oxygen species level acceleration, mitochondria abnormalities and lipid droplet accumulation. Our results suggest that SWS/NTE/PNPLA6 dysfunction in neurons induces oxidative stress and lipid metabolism alterations, involving mitochondria dynamics and lipid droplet turnover in neurodegeneration pathogenesis. We propose that there is a complex mechanism in neurological diseases such as hereditary spastic paraplegia, which includes a stress reaction, engaging mitochondria, lipid droplets and endoplasmic reticulum interplay.     

Ultrasound-assisted production of bioethanol by simultaneous saccharification and fermentation of corn meal

An ultrasound-assisted liquefaction as a pretreatment for bioethanol production by simultaneous saccharification and fermentation (SSF) of corn meal using Saccharomyces cerevisiae var. ellipsoideus yeast in a batch system was studied. Ultrasound pretreatment (at a frequency of 40 kHz) was performed at different sonication times and temperatures, before addition of liquefying enzyme. An optimal duration of the treatment of 5 min and sonication temperature of 60 °C were selected, taking into account glucose concentration after the liquefaction step. Under the optimum conditions an increase of glucose concentration of 6.82% over untreated control sample was achieved. Furthermore, the SSF process kinetics was assessed and determined, and the effect of ultrasound pretreatment on an increase of ethanol productivity was investigated. The obtained results indicated that the ultrasound pretreatment could increase the ethanol concentration by 11.15% (compared to the control sample) as well as other significant process parameters. In this case, the maximum ethanol concentration of 9.67% w/w (which corresponded to percentage of the theoretical ethanol yield of 88.96%) was achieved after 32 h of the SSF process. A comparison of scanning electron micrographs of the ultrasound-pretreated and untreated samples of corn meal suspensions showed that the ultrasound stimulated degradation of starch granules and release of glucose, and thereby accelerated the starch hydrolysis due to the cavitation and acoustic streaming caused by the ultrasonic action.