Selenium-dependent glutathione peroxidase 1 regulates transcription of elongase 3 in murine tissues.

We have previously shown dysregulated lipid metabolism in tissues of glutathione peroxidase 1 (GPX1) overexpressing (OE) or deficient (KO) mice. This study explored underlying mechanisms of GPX1 in regulating tissue fatty acid (FA) biosynthesis. GPX1 OE, KO, and wild-type (WT) mice (n = 5, male, 3-6 months old) were fed a Se-adequate diet (0.3 mg/kg) and assayed for liver and adipose tissue FA profiles and mRNA levels of key enzymes of FA biosynthesis and redox-responsive transcriptional factors (TFs). These three genotypes of mice (n = 5) were injected intraperitoneally with diquat, ebselen, and N-acetylcysteine (NAC) at 10, 50, and 50 mg/kg of body weight, respectively, and killed at 0 and 12 h after the injections to detect mRNA levels of FA elongases and desaturases and the TFs in the liver and adipose tissue. A luciferase reporter assay with targeted deletions of mouse Elovl3 promoter was performed to determine transcriptional regulations of the gene by GPX1 mimic ebselen in HEK293T cells. Compared with WT, GPX1 OE and KO mice had 9-42% lower (p < 0.05) and 36-161% higher (p < 0.05) concentrations of C20:0, C22:0, and C24:0 in these two tissues, respectively, along with reciprocal increases and decreases (p < 0.05) of Elovl3 transcripts. Ebselen and NAC decreased (p < 0.05), whereas diquat decreased (p < 0.05), Elovl3 transcripts in the two tissues. Overexpression and knockout of GPX1 decreased (p < 0.05) and increased (p < 0.05) ELOVL3 levels in the two tissues, respectively. Three TFs (GABP, SP1, and DBP) were identified to bind the Elovl3 promoter (-1164/+33 base pairs). Deletion of DBP (-98/-86 base pairs) binding domain in the promoter attenuated (13%, p < 0.05) inhibition of ebselen on Elovl3 promoter activation. In summary, GPX1 overexpression down-regulated very long-chain FA biosynthesis via transcriptional inhibition of the Elovl3 promoter activation.

Evidence and Metabolic Implications for a New Non-Canonical Role of Cu-Zn Superoxide Dismutase.

Copper-zinc superoxide dismutase 1 (SOD1) has long been recognized as a major redox enzyme in scavenging superoxide radicals. However, there is little information on its non-canonical role and metabolic implications. Using a protein complementation assay (PCA) and pull-down assay, we revealed novel protein-protein interactions (PPIs) between SOD1 and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) or epsilon (YWHAE) in this research. Through site-directed mutagenesis of SOD1, we studied the binding conditions of the two PPIs. Forming the SOD1 and YWHAE or YWHAZ protein complex enhanced enzyme activity of purified SOD1 in vitro by 40% (p < 0.05) and protein stability of over-expressed intracellular YWHAE (18%, p < 0.01) and YWHAZ (14%, p < 0.05). Functionally, these PPIs were associated with lipolysis, cell growth, and cell survival in HEK293T or HepG2 cells. In conclusion, our findings reveal two new PPIs between SOD1 and YWHAE or YWHAZ and their structural dependences, responses to redox status, mutual impacts on the enzyme function and protein degradation, and metabolic implications. Overall, our finding revealed a new unorthodox role of SOD1 and will provide novel perspectives and insights for diagnosing and treating diseases related to the protein.

Complete and efficient conversion of plant cell wall hemicellulose into high-value bioproducts by engineered yeast.

Plant cell wall hydrolysates contain not only sugars but also substantial amounts of acetate, a fermentation inhibitor that hinders bioconversion of lignocellulose. Despite the toxic and non-consumable nature of acetate during glucose metabolism, we demonstrate that acetate can be rapidly co-consumed with xylose by engineered Saccharomyces cerevisiae. The co-consumption leads to a metabolic re-configuration that boosts the synthesis of acetyl-CoA derived bioproducts, including triacetic acid lactone (TAL) and vitamin A, in engineered strains. Notably, by co-feeding xylose and acetate, an enginered strain produces 23.91 g/L TAL with a productivity of 0.29 g/L/h in bioreactor fermentation. This strain also completely converts a hemicellulose hydrolysate of switchgrass into 3.55 g/L TAL. These findings establish a versatile strategy that not only transforms an inhibitor into a valuable substrate but also expands the capacity of acetyl-CoA supply in S. cerevisiae for efficient bioconversion of cellulosic biomass.

Recoverable Liquid Metal Paste with Reversible Rheological Characteristic for Electronics Printing.

Gallium-based liquid metals are applied in the fabrication of soft electronics because of their conductivity and flexibility. However, the large surface tension and weak adhesion of liquid metals limit the available printing substrates. Recent researches indicate that amalgamating metal particles can turn liquid metal from fluid into a paste which has superb electrical conductivity, plasticity, and strong adhesion to substrates. In this work, a recoverable liquid metal paste was made by mixing eutectic Ga-In alloy and nonmetallic SiO2 (quartz) particles (Ga-In-SiO2 paste, called GIS). GIS has excellent conductivity and printable properties similar to those of previously reported liquid metal pastes. Furthermore, the bonding between Ga-In alloy and quartz particles is reversible. In acidic or alkaline solution, Ga-In alloy can be separated from quartz particles and agglomerated to bulk by stirring. Moreover, the study of the mechanism of adhesion behavior suggests that extruding fresh liquid metal droplets to form more oxide and shearing friction are the critical factors for adhesion. This work proposed a new liquid metal paste with a reversible rheological property and promoted the understanding of the working principle of liquid metal paste.

Natural cryoprotectants combinations of l-proline and trehalose for red blood cells cryopreservation.

Cryopreservation of red blood cells (RBCs) holds great potential benefits for supplying transfusion timely in emergencies. Currently, glycerol is the main cryoprotectant permitted in clinical therapy for RBCs cryopreservation, but its broad application is limited by the toxicity and complex deglycerolization process. Successful cryopreservation of RBCs using more effective materials should be studied to reduce freezing damage, increase biocompatibility, and save processing time. Herein, a simple protocol using natural cryoprotectants combinations of l-proline and trehalose attains a low degree of hemolysis (11.2 ±â€¯2.73%) after thawing compared to glycerol. Furthermore, the morphology of RBCs and the activities of Na+/K+-ATPase and Ca2+/Mg2+-ATPase maintain well. Further mechanism study shows that l-proline plays an important role in decreasing the freezing points and inhibiting the growth of ice crystal by permeating into cells during the freezing process. While trehalose works as an inhibitor of ice growth in the freezing process and ice recrystallization in the thawing process. This simple l-proline & trehalose combinations protocol is a promising method to replace current time-consuming and labor-intensive cryopreservation methods of RBCs.

L-proline feeding for augmented freeze tolerance of Camponotus japonicus Mayr.

The successful cryopreservation of organs is a strong and widespread demand around the world but faces great challenges. The mechanisms of cold tolerance of organisms in nature inspirit researchers to find new solutions for these challenges. Especially, the thermal, mechanical, biological and biophysical changes during the regulation of freezing tolerance process should be studied and coordinated to improve the cryopreservation technique and quality of complex organs. Here the cold tolerance of the Japanese carpenter ants, Camponotus japonicus Mayr, was greatly improved by using optimal protocols and feeding on L-proline-augmented diets for 5 days. When cooling to -27.66 °C, the survival rate of frozen ants increased from 37.50% ±â€¯1.73% to 83.88% ±â€¯3.67%. Profiling of metabolites identified the concentration of whole-body L-proline of ants increased from 1.78 to 4.64 ng g-1 after 5-day feeding. High L-proline level, together with a low rate of osmotically active water and osmotically inactive water facilitated the prevention of cryoinjury. More importantly, gene analysis showed that the expression of ribosome genes was significantly up-regulated and played an important role in manipulating freezing tolerance. To the best of our knowledge, this is the first study to link genetic variation to the enhancement of ants' cold tolerance by feeding exogenous cryoprotective compound. It is worth noting that the findings provide the theoretical and technical foundation for the cryopreservation of more complex tissues, organs, and living organisms.

Nanoparticle-mediated cryosurgery for tumor therapy.

Cryosurgery is an energy-based surgical technique. It is minimally invasive and has fewer side effects than surgical resection. However, its insufficient freezing to target tumor and unavoidable injury to healthy tissue have restricted its success. Nano-cryosurgery is the combination of cryogenic biomedicine and nanotechnology. Its principle is to introduce a nanoparticle solution into target tissues to maximize heat transfer, lower the end temperature, increase ice ball formation, and prevent healthy tissues from being frozen. This review covers common nanoplatforms for nano-cryosurgery. The characteristics, advantages, potential challenges, future prospects of applying nano-cryosurgery are discussed in detail.

In vivo experiments and numerical investigations on nanocryosurgical freezing of target tissues with large blood vessels.

This study presented the first in vivo animal experiments of using nano-cryosurgical modality to completely freezing tumor tissues embedded with large blood vessels, which is a tough issue to tackle otherwise. Three-dimensional theoretical simulations were also performed on the complex freezing problems by considering flow and heat transfer of blood flow in large vessels. According to the experimental measurements and numerical predictions, injecting the nanoparticles with high thermal conductivity into the freezing target can significantly reduce the heating effect of blood vessel, shorten the freezing time, and enlarge the freezing range. Most importantly, the introduction of nanoparticles successfully overcomes the classical challenges in completely ablating the tumor region with large blood vessel and enhancing the freezing efficacy of cryosurgery. This investigation consolidates the practical and theoretical foundation for nano-cryosurgery which suggests a highly efficient freezing strategy for treating late stage tumor.

A new nano-cryosurgical modality for tumor treatment using biodegradable MgO nanoparticles.

A new conceptual modality for nano-cryosurgical ablation of tumors is proposed in this article. The main strategy is to apply MgO nanoparticles (NPs), which are nontoxic, biodegradable, and have few side-effects on the human body, to mediate the freezing procedure effectively. Detailed investigation via animal experiments and nucleation analysis demonstrated that delivery of MgO NPs into the target tissues would significantly improve the cryosurgical outcome. The formation of an iceball during the freezing process is accelerated and enlarged due to the excellent thermal properties of MgO NPs. In addition this method could promote the generation of ice nuclei and thus enhance cryoinjury to the target cells. Therefore, combining the biodegradability and nontoxicity of MgO NPs with their relatively lightweight properties, excellent thermal properties would help develop a high-performance cryosurgery. These findings may lead to methods for safe and targeted nano-cryosurgery and possibly break through the barriers facing current clinical treatments of cancer. FROM THE CLINICAL EDITOR: Cryosurgery is a promising evolving modality to address malignancies. The work presented in this paper may add a novel concept to the field of nanomedicine by demonstrating that MgO nanoparticles enable more efficient ice-ball formation and cryoinjury in the target tissue.