Inhibition of tumor propellant glutathione peroxidase 4 induces ferroptosis in cancer cells and enhances anticancer effect of cisplatin

Glutathione peroxidase 4 (GPX4) has been confirmed to inhibit ferroptosis in cancer cells, however, whether GPX4 serves as an oncogene is not clear. In this study, the expression of GPX4 and its influence to survival of patients with cancer were analyzed via public databases. Furthermore, the epigenetic regulation of GPX4 and the relation between GPX4 and chemoresistance of different anticancer drugs was also detected. Most importantly, cytological assays were performed to investigate the function of GPX4 in cancer cells. The results showed that GPX4 was higher expressed in cancer tissues than normal and was negatively associated with prognosis of patients. Furthermore, at upstream of GPX4 there was low DNA methylation sites and enhanced level of H3K4me3 and H3K27ac, indicating that high level of GPX4 in cancer may resulted from epigenetic regulation. Moreover, GPX4 was positively related to chemoresistance of anticancer drugs L-685458, lapatinib, palbociclib, and topotecan. In addition, GPX4 may potentially be involved in translation of protein, mitochondrial respiratory chain complex I assembly, electron transport oxidative phosphorylation, nonalcoholic fatty liver disease, and metabolic pathways. Finally, we detected that GPX4 inhibited ferroptosis in cancer cells, the inhibition of GPX4 via RSL3 could enhance the anticancer effect of cisplatin in vitro and in vivo. In conclusion, GPX4 acts as an oncogene and inhibits ferroptosis in cancer cells, the anticancer effect of cisplatin can be enhanced by GPX4 inhibition.     

Body mass and behavior in Swiss mice subjected to continuous or discontinuous food restriction and refeeding

Food restriction (FR) is hypothesized to decrease body fat content of an animal and thus prevent obesity. However, the response of energy budget to a continuous (CFR) or discontinuous FR (DFR) remains inconsistent. In the present study, effects of CFR or DFR and refeeding on energy budget and behavior were examined in male Swiss mice. CFR significantly decreased the energy expenditure associated with basal metabolic rate (BMR) and activity behavior, but not sufficiently to compensate for energy deficit and thus resulted in lower body mass and fat content. DFR mice had a significantly higher food intake on ad libitum days and showed increases in BMR and activity after 4 weeks’ DFR, which might resulted in lower body mass and less body fat than controls. After being refed ad libitum, both CFR and DFR mice had similar body mass, BMR, and behavioral patterns to controls but had 95% and 75% higher fat content. This suggested that not only CFR but also DFR would be a significant factor in the process of obesity for animals that were refed ad libitum. It also indicated that food restriction interrupted many times by periods of ad libitum feeding had the same long-term effects like continuous underfeeding.     

The FYVE Domain of Smad Anchor for Receptor Activation (SARA) Is Required to Prevent Skin Carcinogenesis,but Not in Mouse Development

Smad Anchor for Receptor Activation (SARA) has been reported as a critical role in TGF-β signal transduction by recruiting non-activated Smad2/3 to the TGF-β receptor and ensuring appropriate subcellular localization of the activated receptor-bound complex. However, controversies still exist in previous reports. In this study, we describe the expression of two SARA isoforms, SARA₁ and SARA₂, in mice and report the generation and characterization of SARA mutant mice with FYVE domain deletion. SARA mutant mice developed normally and showed no gross abnormalities. Further examination showed that the TGF-β signaling pathway was indeed altered in SARA mutant mice, with the downregulation of Smad2 protein expression. The decreasing expression of Smad2 was caused by enhancing Smurf2-mediated proteasome degradation pathway. However, the internalization of TGF-β receptors into the early endosome was not affected in SARA mutant mouse embryonic fibroblasts (MEFs). Moreover, the downregulation of Smad2 in SARA mutant MEFs was not sufficient to disrupt the diverse cellular biological functions of TGF-β signaling, including growth inhibition, apoptosis, senescence, and the epithelial-to-mesenchymal transition. Our results indicate that SARA is not involved in the activation process of TGF-β signal transduction. Using a two-stage skin chemical carcinogenesis assay, we found that the loss of SARA promoted skin tumor formation and malignant progression. Our data suggest a protective role of SARA in skin carcinogenesis.     

Diverse phylogeny and morphology of magnetite biomineralized by magnetotactic cocci

Magnetotactic bacteria (MTB) are diverse prokaryotes that produce magnetic nanocrystals within intracellular membranes (magnetosomes). Here, we present a large-scale analysis of diversity and magnetosome biomineralization in modern magnetotactic cocci, which are the most abundant MTB morphotypes in nature. Nineteen novel magnetotactic cocci species are identified phylogenetically and structurally at the single-cell level. Phylogenetic analysis demonstrates that the cocci cluster into an independent branch from other Alphaproteobacteria MTB, that is, within the Etaproteobacteria class in the Proteobacteria phylum. Statistical analysis reveals species-specific biomineralization of magnetosomal magnetite morphologies. This further confirms that magnetosome biomineralization is controlled strictly by the MTB cell and differs among species or strains. The post-mortem remains of MTB are often preserved as magnetofossils within sediments or sedimentary rocks, yet paleobiological and geological interpretation of their fossil record remains challenging. Our results indicate that magnetofossil morphology could be a promising proxy for retrieving paleobiological information about ancient MTB.     

Development and application of photoautotrophic micropropagation plant system

Research has revealed that most chlorophyllous explants/plants in vitro have the ability to grow photoautotrophically (without sugar in the culture medium), and that the low or negative net photosynthetic rate of plants in vitro is not due to poor photosynthetic ability, but to the low CO₂ concentration in the air-tight culture vessel during the photoperiod. Moreover, numerous studies have been conducted on improving the in vitro environment and investigating its effects on growth and development of cultures/plantlets on nearly 50 species since the concept of photoautotrophic micropropagation was developed more than two decades ago. These studies indicate that the photoautotrophic growth in vitro of many plant species can be significantly promoted by increasing the CO₂ concentration and light intensity in the vessel, by decreasing the relative humidity in the vessel, and by using a fibrous or porous supporting material with high air porosity instead of gelling agents such as agar. This paper reviews the development and characteristics of photoautotrophic micropropagation systems and the effects of environmental conditions on the growth and development of the plantlets. The commercial applications and the perspective of photoautotrophic micropropagation systems are discussed.     

The incertae sedis <Emphasis Type="Italic">Carpathoporella</Emphasis> Dragastan, 1995, from the Lower Cretaceous of Albania: skeletal elements (sclerites,internodes/branches,holdfasts) of colonial octocorals

The incertae sedis Carpathoporella Dragastan, 1995, reported from the Lower Cretaceous of the Western Tethyan domain, is usually interpreted as remains of calcareous algae (Dasycladales or Characeae). New thin-section material from the Aptian of Albania sheds light not only on its biogenic nature but also on the morphological variability of this taxon. In fact, Carpathoporella represents the debris of colonial, bushy, most likely gorgonid octocorals with tuberculated spheroids that may be fused at least near the basal root-like holdfast. Colony branching originates from longitudinally grooved calcareous branches or internodes. Possible relationships to other Upper Cretaceous to Palaeogene genera are discussed and a revised critical inventory of Cretaceous octocorals is presented. Due to the evidenced morphological features, Carpathoporella could either represent an ancestral isidid octocoral of the order Alcyonacea such as Moltkia Steenstrup or, due to the likely primary aragonitic skeletal mineralogy, a representative of Epiphaxum Lonsdale of the order Helioporacea. Due to morphological analogies, the new combination Carpathoporella elliotti (Radoičić) is proposed. In any case, the Lower Cretaceous record from Tethyan peri-reefal shallow-water carbonates is highlighted since numerous skeletal findings of fossil gorgonid Octocorallia were so far only known from Upper Cretaceous and younger strata of outer shelf environments of the boreal realm. The origin of deep-water Upper Cretaceous octocorals from Lower Cretaceous shallow-water taxa such as Carpathoporella is proposed as a possible further example of onshore/offshore evolutionary pattern.     

Designing Commensurate and Incommensurate Resonances for Enhanced Dipole Emission in Coupled Plasmonic Nanorods

Plasmonic nanorods and their clusters are the fundamental units in plasmonic nanoantenna engineering. A theory that can predict the resonance of single nanorod already exists but is in lack for a heterodimer. Here, we propose a model combining the effective circuit theory for the response of spherical nanoparticles together with standard transmission line theory for hemispherically capped nanorod antennas. The resonances of multiple orders are predictable by defining the reflection phase at the terminals of such antennas, in both symmetric and asymmetric coupled nanorods. The theoretical results compare favorably with full-wave finite element numerical calculations. By the analytical formula, it is easy to control the length of the antennas for regulating the cooperative resonant properties and consequently the radiation characteristics of a nearby electric dipole. Consequently, we obtain both commensurate and incommensurate resonance features in such nanorod-based heterodimer antennas, showing respectively cumulative and selective responses from the individual nanorods.     

Elevation of Serum Dopamine-β-hydroxylase Activity with Forced Immobilization

THE formation of the neurotransmitter noradrenaline from 3,4-dihydroxyphenylethylamine (dopamine) is catalysed by the enzyme dopamine-β-hydroxylase (DBH)¹. This enzyme is associated both with the catecholamine-containing chromaffin granules in the adrenal medulla^2,3 and with the vesicular structures in sympathetic nerve terminals which contain catecholamines⁴. Furthermore, DBH activity is released with catecholamines into the perfusate after stimulation of either the isolated perfused adrenal gland⁵ or the isolated perfused spleen^6–8. DBH activity has been reported in the serum of both man and the rat^9,10. This activity is similar to adrenal and sympathetic nerve DBH activity with regard to cofactor requirements, oxygen requirement and kinetic characteristics^9,10. It has been suggested that serum DBH activity might be present as a result of release of enzyme with catecholamines from the adrenal glands and sympathetic nerves. If this is the case, serum DBH activity might be a useful and convenient index of sympathetic-adrenal activity. The work described here was undertaken to investigate both the source of the serum DBH and the effect on this activity of forced immobilization, a procedure which has been used as a model of stress and which has been shown to release catecholamines from the adrenal gland and increase catecholamine excretion¹¹.