Investigation of the Antiproliferative Properties of Natural Sesquiterpenes from Artemisia asiatica and Onopordum acanthium on HL-60 Cells in Vitro

Plants and plant extracts play a crucial role in the research into novel antineoplastic agents. Four sesquiterpene lactones, artecanin (1), 3β-chloro-4α,10α-dihydroxy-1α,2α-epoxy-5α,7αH-guaia-11(13)-en-12,6α-olide (2), iso-seco-tanapartholide 3-O-methyl ether (3) and 4β,15-dihydro-3-dehydrozaluzanin C (4), were isolated from two traditionally used Asteraceae species (Onopordum acanthium and Artemisia asiatica). When tested for antiproliferative action on HL-60 leukemia cells, these compounds exhibited reasonable IC₅₀ values in the range 3.6–13.5 μM. Treatment with the tested compounds resulted in a cell cycle disturbance characterized by increases in the G1 and G2/M populations, while there was a decrease in the S phase. Additionally, 1–3 elicited increases in the hypodiploid (subG1) population. The compounds elicited concentration-dependent chromatin condensation and disruption of the membrane integrity, as revealed by Hoechst 33258–propidium staining. Treatment for 24 h resulted in significant increases in activity of caspases-3 and -9, indicating that the tested sesquiterpenes induced the mitochondrial pathway of apoptosis. The proapoptotic properties of the sesquiterpene lactones were additionally demonstrated withannexin V staining. Compounds 1 and 2 increased the Bax/Bcl-2 expression and decreased the expressions of CDK1 and cyclin B2, as determined at the mRNA level by means of RT-PCR. These experimental results indicate that sesquiterpene lactones may be regarded as potential starting structures for the development of novel anticancer agents.     

Current Trends in Pretreatment and Fractionation of Lignocellulose as Reflected in Industrial Patent Activities

The pretreatment process to disintegrate lignocellulose and to fractionate its three main components hemicellulose, cellulose, and lignin, is a crucial step to enable sustainable and economic value chains based on biomass feedstock. This review provides an overview of the recent patenting activities on pretreatment. Most of these activities focus on optimization of different known processes to improve economics, such as increased catalyst efficiency, effluents recirculation, or lignin valorization. However, also a number of patents and demonstration activities based on emerging concepts for pretreatments are observed.     

Formation Mechanism of Alkyl Nitrites,Valuable Intermediates in C1-Upgrading Chemistry and Oxidation Processes

In this contribution we use computational tools to investigate the reaction of alcohol substrates with reactive nitrogen oxide species such as N₂O₃ and N₂O₄, leading to the formation of alkyl nitrites. These nitrites are interesting intermediates which can be processed to various valuable chemicals such as ketones/aldehydes and dimethyl oxalate while regenerating NO _x . As such, NO _x is used as an oxidation mediator, converting alcohol substrates to more reactive nitrites which can be selectively converted to more desired compounds, closing a catalytic cycle in NO _x species.     

Design of an Ultrafast G Protein Switch Based on a Mouse Melanopsin Variant

The primary goal of optogenetics is the light-controlled noninvasive and specific manipulation of various cellular processes. Herein, we present a hybrid strategy for targeted protein engineering combining computational techniques with electrophysiological and UV/visible spectroscopic experiments. We validated our concept for channelrhodopsin-2 and applied it to modify the less-well-studied vertebrate opsin melanopsin. Melanopsin is a promising optogenetic tool that functions as a selective molecular light switch for G protein-coupled receptor pathways. Thus, we constructed a model of the melanopsin G_q protein complex and predicted an absorption maximum shift of the Y211F variant. This variant displays a narrow blue-shifted action spectrum and twofold faster deactivation kinetics compared to wild-type melanopsin on G protein-coupled inward rectifying K⁺ (GIRK) channels in HEK293 cells. Furthermore, we verified the in vivo activity and optogenetic potential for the variant in mice. Thus, we propose that our developed concept will be generally applicable to designing optogenetic tools.     

Inhibition of Hepatitis C Replication by Targeting the Molecular Chaperone Hsp90: Synthesis and Biological Evaluation of 4,5,6,7-Tetrahydrobenzo[1,2-d]thiazole Derivatives

Cellular chaperones that belong to the heat-shock protein 90 (Hsp90) family are a prerequisite for successful viral propagation for most viruses. The hepatitis C virus (HCV) uses Hsp90 for maturation, folding, and modification of viral proteins. Based on our previous discovery that marine alkaloid analogues with a 4,5,6,7-tetrahydrobenzo[1,2-d]thiazole-2-amine structure show inhibition of HCV replication and binding to Hsp90, a series of twelve novel compounds based on this scaffold was designed and synthesized. The aim was improved Hsp90 affinity and anti-HCV activity. Through structural optimization, improved binding to Hsp90 and specific HCV inhibition in genotype 1b and 2a replicon models was achieved for three compounds belonging to the newly synthesized series. Furthermore, these compounds efficiently inhibited replication of full-length HCV genotype 2a in a reporter virus RNA assay with IC₅₀ values ranging from 0.03 to 0.6 μm .     

3D‐Printing of High‐κ Thiol‐Ene Resins with Spiro‐Orthoesters as Anti‐Shrinkage Additive

Tri(ethylene glycol) divinyl ether and the spiro‐orthoester 2‐((allyloxy)methy)‐1,4,6‐trioxospiro[4.4]nonane can be formulated in different ratios and crosslinked by thiol‐ene reactions. The spiro‐orthoester is used as anti‐shrinkage additive, enabling shrinkage reduction of up to 39%. Addition of a radical photoinitiator for the thiol‐ene reaction and a cationic photoinitiator for the double ring‐opening of the spiro‐orthoester enables dual‐curing for application in 3D‐printing. The formulation free of the spiro‐orthoester shows gelation during the printing process and, correspondingly, low resolution. The formulations containing the spiro‐orthoester exhibit higher resolutions in the range of 50 µm. The resins containing mixtures of tri(ethylene glycol) divinyl ether and the spiro‐orthoester show permittivities as high as 10⁴. The dielectric loss factor of the resins is in the range of 0.5–7.6, and the conductivity in the range of 1.3?10^?11 to 2.0?10^?11 S cm^?1. These high‐κ materials can be 3D‐printed by digital light processing for the next generation of electronic materials.     

Increase in energy and land use by a bio-based chemical industry

About 80% of the chemical products are still based on crude oil. Bio-based materials will increasingly gain importance. As the fraction of oxygen is normally higher in biomass than in crude oil as well as in the derived conventional products, this implies a need to develop new synthesis pathways. Depending on the types of new synthesis pathways, the effects of a complete raw-material change on land and exergy use differ. Here, different synthesis pathways starting from glucose and plant oil to different kinds of end products are evaluated utilizing material and exergy balances. These evaluations are carried out under today's and future conditions and constraints, like yield, demand of organic chemicals and world population. The analysis in this paper shows that the land and energy use can be significantly reduced, if the products are adapted to the chemical structure of their bio-based feedstock.     

Reactive,nonreactive, and flash spark plasma sintering of Al2O3/SiC composites—A comparative study

The influence of different SPS-based methods, that is, conventional spark plasma sintering (SPS), flash SPS (FSPS), and reactive SPS (RSPS) on the properties of Al₂O₃/SiC composite was investigated. It was shown that the application of preliminary high energy ball milling of the powders significantly enhances the sinterability of the ceramics. It was also demonstrated that FSPS provides unique conditions for rapid, that is, less than a minute, consolidation of refractory ceramics. The Al₂O₃-20 wt% SiC composite produced by FSPS possesses the highest relative density (~99%), fracture toughness (7.5 MPa m^1/2), hardness (20.3 GPa) and wear resistance among all ceramics produced by other SPS-based approaches with dwelling time 10 minutes. The RSPS ceramics hold the highest Young's modulus (390 GPa). Substitution of micron-sized Al₂O₃ particles by nano alumina does not lead to measurable enhancement of the mechanical properties.     

Fucoidans as Potential Therapeutics for Age-Related Macular Degeneration—Current Evidence from In Vitro Research

Age-related macular degeneration (AMD) is the major reason for blindness in the industrialized world with limited treatment options. Important pathogenic pathways in AMD include oxidative stress and vascular endothelial growth factor (VEGF) secretion. Due to their bioactivities, fucoidans have recently been suggested as potential therapeutics. This review gives an overview of the recent developments in this field. Recent studies have characterized several fucoidans from different species, with different molecular characteristics and different extraction methods, in regard to their ability to reduce oxidative stress and inhibit VEGF in AMD-relevant in vitro systems. As shown in these studies, fucoidans exhibit a species dependency in their bioactivity. Additionally, molecular properties such as molecular weight and fucose content are important issues. Fucoidans from Saccharina latissima and Laminaria hyperborea were identified as the most promising candidates for further development. Further research is warranted to establish fucoidans as potential therapeutics for AMD.