A novel remediation strategy of mixed calcium peroxide and degrading bacteria for polycyclic aromatic hydrocarbon contaminated water.

Polycyclic aromatic hydrocarbons (PAHs) are a class of toxic organic pollutants commonly detected in the aqueous phase. Traditional biodegradation is inefficient and advanced oxidation technologies are expensive. In the current study, a novel strategy was developed using calcium peroxide (CP) and PAH-degrading bacteria (PDB) to effectively augment PAH degradation by 28.62-59.22%. The PDB consisted of the genera Acinetobacter, Stenotrophomonas, and Comamonas. Applying the response surface model (RSM), the most appropriate parameters were identified, and the predictive degradation rates of phenanthrene (Phe), pyrene (Pyr), and ΣPAHs were 98%, 76%, and 84%, respectively. The constructed mixed system could reduce 90% of Phe and more than 60% of ΣPAHs and will perform better at pH 5-7 and lower salinity. Because PAHs tend to bind to dissolved organic matter (DOM) with larger molecular weights, humic acid (HA) had a larger negative effect on the PAH-degradation efficiency of the CP-PDB mixed system than fulvic acid (FA). The proposed PAH-degradation pathways in the mixed system were based on the detection of intermediates at different times. The investigation constructed and optimized a novel environmental PAH-degradation strategy. The synergistic application of PDB and oxidation was extended for organic contaminant degradation in aqueous environments.

Glutathione Supplementation Prevents Neonatal Parenteral Nutrition-Induced Short- and Long-Term Epigenetic and Transcriptional Disruptions of Hepatic H2O2 Metabolism in Guinea Pigs.

The parenteral nutrition (PN) received by premature newborns is contaminated with peroxides that induce global DNA hypermethylation via oxidative stress. Exposure to peroxides could be an important factor in the induction of chronic diseases such as those observed in adults who were born preterm. As endogenous H2O2 is a major regulator of glucose-lipid metabolism, our hypothesis was that early exposure to PN induces permanent epigenetic changes in H2O2 metabolism. Three-day-old guinea pigs were fed orally (ON), PN or glutathione-enriched PN (PN+GSSG). GSSG promotes endogenous peroxide detoxification. After 4 days, half the animals were sacrificed, and the other half were fed ON until 16 weeks of age. The liver was harvested. DNA methylation and mRNA levels were determined for the SOD2, GPx1, GCLC, GSase, Nrf2 and Keap1 genes. PN induced GPx1 hypermethylation and decreased GPx1, GCLC and GSase mRNA. These findings were not observed in PN+GSSG. PN+GSSG induced Nrf2 hypomethylation and increased Nrf2 and SOD2 mRNA. These observations were independent of age. In conclusion, in neonatal guinea pigs, PN induces epigenetic changes, affecting the expression of H2O2 metabolism genes. These changes persist for at least 15 weeks after PN. This disruption may signify a permanent reduction in the capacity to detoxify peroxides.

Enzymatic machinery of wood-inhabiting fungi that degrade temperate tree species.

Deadwood provides habitat for fungi and serves diverse ecological functions in forests. We already have profound knowledge of fungal assembly processes, physiological and enzymatic activities, and resulting physico-chemical changes during deadwood decay. However, in situ detection and identification methods, fungal origins, and a mechanistic understanding of the main lignocellulolytic enzymes are lacking. This study used metaproteomics to detect the main extracellular lignocellulolytic enzymes in 12 tree species in a temperate forest that have decomposed for 8 ½ years. Mainly white-rot (and few brown-rot) Basidiomycota were identified as the main wood decomposers, with Armillaria as the dominant genus; additionally, several soft-rot xylariaceous Ascomycota were identified. The key enzymes involved in lignocellulolysis included manganese peroxidase, peroxide-producing alcohol oxidases, laccase, diverse glycoside hydrolases (cellulase, glucosidase, xylanase), esterases, and lytic polysaccharide monooxygenases. The fungal community and enzyme composition differed among the 12 tree species. Ascomycota species were more prevalent in angiosperm logs than in gymnosperm logs. Regarding lignocellulolysis as a function, the extracellular enzyme toolbox acted simultaneously and was interrelated (e.g. peroxidases and peroxide-producing enzymes were strongly correlated), highly functionally redundant, and present in all logs. In summary, our in situ study provides comprehensive and detailed insight into the enzymatic machinery of wood-inhabiting fungi in temperate tree species. These findings will allow us to relate changes in environmental factors to lignocellulolysis as an ecosystem function in the future.

In Situ Mitochondrial Biomineralization for Drug-Free Cancer Therapy.

The common clinical chemotherapy often brings serious side effects to patients, mainly due to the off-target and leakage of toxic drugs. However, this is fatal for some specific clinical tumors, such as brain tumors and neuroma. This study performs a drug-free approach by encapsulating black phosphorus (BP) and calcium peroxide (CaO2) in liposomes with surface-modified triphenylphosphonium (BCLT) to develop mitochondria targeting calcification for cancer therapy without damaging normal cells. BCLT preferentially accumulates inside tumor mitochondria and then is activated by near-infrared (NIR) laser irradiation to produce abundant PO4 3- and Ca2+ to accelerate in situ mitochondrial mineralization, leading to mitochondrial dysfunction and cancer cell death. More importantly, both PO4 3- and Ca2+ are essential components of metabolism in the body, and random gradient diffusion or premature leakage does not cause damage to adjacent normal cells. This achievement promises to be an alternative to conventional chemotherapy in clinical practice for many specific tumor types.

Enhancing cold and drought tolerance in cotton: a protective role of SikCOR413PM1.

The present study explored the potential role of cold-regulated plasma membrane protein COR413PM1 isolated from Saussurea involucrata (Matsum. & Koidz)(SikCOR413PM1), in enhancing cotton (Gossypium hirsutum) tolerance to cold and drought stresses through transgenic methods. Under cold and drought stresses, the survival rate and the fresh and dry weights of the SikCOR413PM1-overexpressing lines were higher than those of the wild-type plants, and the degree of leaf withering was much lower. Besides, overexpressing SikCOR413PM1 overexpression increased the relative water content, reduced malondialdehyde content and relative conductivity, and elevated proline and soluble sugar levels in cotton seedlings. These findings suggest that SikCOR413PM1 minimizes cell membrane damage and boosts plant stability under challenging conditions. Additionally, overexpression of this gene upregulated antioxidant enzyme-related genes in cotton seedlings, resulting in enhanced antioxidant enzyme activity, lowered peroxide content, and reduced oxidative stress. SikCOR413PM1 overexpression also modulated the expression of stress-related genes (GhDREB1A, GhDREB1B, GhDREB1C, GhERF2, GhNAC3, and GhRD22). In field trials, the transgenic cotton plants overexpressing SikCOR413PM1 displayed high yields and increased environmental tolerance. Our study thus demonstrates the role of SikCOR413PM1 in regulating stress-related genes, osmotic adjustment factors, and peroxide content while preserving cell membrane stability and improving cold and drought tolerance in cotton.

New insights into peroxide toxicology: sporulenes help Bacillus subtilis endospores from hydrogen peroxide.

AIM: The purpose of the present study was to understand the possible events involved in the toxicity of hydrogen peroxide (H2O2) to wild and sporulene-deficient spores of Bacillus subtilis, as H2O2 was previously shown to have deleterious effects. METHODS AND RESULTS: The investigation utilized two strains of B. subtilis, namely the wild-type PY79 (WT) and the sporulene-deficient TB10 (ΔsqhC mutant). Following treatment with 0.05% H2O2 (v/v), spore viability was assessed using a plate count assay, which revealed a significant decrease in cultivability of 80% for the ΔsqhC mutant spores. Possible reasons for the loss of spore viability were investigated with microscopic analysis, dipicholinic acid (DPA) quantification and propidium iodide (PI) staining. Microscopic examinations revealed the presence of withered and deflated morphologies in spores of ΔsqhC mutants treated with H2O2, indicating a compromised membrane permeability. This was further substantiated by the absence of DPA and a high frequency (50%-75%) of PI infiltration. The results of fatty acid methyl ester analysis and protein profiling indicated that the potentiation of H2O2-induced cellular responses was manifested in the form of altered spore composition in ΔsqhC B. subtilis. The slowed growth rates of the ΔsqhC mutant and the heightened sporulene biosynthesis pathways in the WT strain, both upon exposure to H2O2, suggested a protective function for sporulenes in vegetative cells. CONCLUSIONS: Sporulenes serve as a protective layer for the inner membrane of spores, thus assuming a significant role in mitigating the adverse effects of H2O2 in WT B. subtilis. The toxic effects of H2O2 were even more pronounced in the spores of the ΔsqhC mutant, which lacks this protective barrier of sporulenes.

Aquaporin-7 Facilitates Proliferation and Adipogenic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells by Regulating Hydrogen Peroxide Transport.

Hydrogen peroxide (H2O2) is a major form of reactive oxygen species that play an important role in the survival, proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). The regulatory mechanisms of H2O2 homeostasis in BMSCs are not fully understood. Here we demonstrate for the first time that aquaglyceroporin AQP7 is a functional peroxiporin expressed in BMSCs and remarkably upregulated upon adipodenic induction. The proliferation ability of BMSCs from AQP7-/- mice was significantly decreased, as indicated by fewer clonal formation and cell cycle arrest compared with wildtype BMSCs. AQP7 deficiency caused accumulation of intracellular generated H2O2 during BMSCs proliferation, leading to oxidative stress and inhibition of PI3K/AKT and STAT3 signaling pathways. After adipogenic induction, however, the AQP7-/- BMSCs exhibited greatly reduced adipogenic differentiation with fewer lipid droplets formation and lower cellular triglycerides content than wildtype BMSCs. In such case AQP7 deficiency was found to diminish import of extracellular H2O2 produced by plasma membrane NADPH Oxidases, resulting in altered AMPK and MAPK signaling pathways and reduced expression of lipogenic genes C/EBPα and PPARγ. Our data revealed a novel regulatory mechanism of BMSCs function through AQP7-mediated H2O2 transport across plasma membrane. AQP7 is a peroxiporin mediating H2O2 transport across the plasma membrane of BMSCs. During proliferation, AQP7 deficiency results in accumulation of intracellular generated H2O2 due to reduced export, which inhibited STAT3 and PI3K/AKT/insulin receptor signaling pathways and cell proliferation. During adipogenic differentiation, however, AQP7 deficiency blocked the uptake of extracelluar H2O2 generated through plasma membrane NOX enzymes. The reduced intracellular H2O2 level causes decreased expression of lipogenic genes C/EBPα and PPARγ due to altered AMPK and MAPK signaling pathways, leading to impaired adipogenic differentiation.

Molecular therapy of cardiac ischemia-reperfusion injury based on mitochondria and ferroptosis.

Excessive death of myocardial cells can lead to various cardiovascular diseases and even develop into heart failure, so developing ideal treatment plans based on pathogenesis is of great significance for cardiopathy. After the heart undergoes ischemia‒reperfusion (I/R), myocardial cells accumulate a large amount of peroxides, leading to mitochondrial dysfunction and inducing ferroptosis. Ferroptosis is a form of iron-dependent regulatory cell death (RCD) caused by imbalanced redox and iron metabolism that leads to severe cell damage through the accumulation of peroxides. The mechanism of ferroptosis is highly correlated with mitochondrial metabolism. Myocardial cells are rich in a large number of mitochondria, which serve as energy supply centers and are prone to producing reactive oxygen species (ROS), providing opportunities for oxidative stress caused by ferroptosis. Ferroptosis is related to various cardiovascular diseases, and potential treatment methods designed around ferroptosis may alter the pathological progression of cardiovascular diseases. Therefore, this review investigates the regulatory mechanisms of ferroptosis, exploring the close pathological and physiological connections between ferroptosis and mitochondrial and cardiac I/R injury. Targeting ferroptosis and mitochondria for intervention may be an effective plan for preventing and treating cardiac I/R injury.

Probing cytoplasmic peroxide metabolism in Shewanella oneidensis.

The facultative anaerobe Shewanella oneidensis respires an extensive set of electron acceptors and, as a consequence, can leak electrons to produce reactive oxygen species such as hydrogen peroxide (H2O2). However, the effects of respiration on cytoplasmic redox homeostasis are poorly characterized in comparison. In the present study, the H2O2 sensor HyPer-3 was deployed to interrogate cytoplasmic peroxide levels of both wild-type and gene deletion mutants lacking peroxide scavenging enzymes following exposure to H2O2. HyPer-3 signals were validated in the S. oneidensis wild-type strain and exhibited a dynamic range of 0-250 µM H2O2. As reported by the HyPer-3 sensor, the cytoplasm of H2O2-perturbed mutant strains lacking periplasmic glutathione peroxidase (PgpD) and double deletion mutants lacking catalase (KatB) and bifunctional catalase-peroxidases (KatG1 or KatG2) contained high H2O2 concentrations. The high cytoplasmic H2O2 concentrations correlated with impaired H2O2 removal rates displayed by the mutant strains. Results of the present study provide the first in vivo interrogation of the redox environment of the S. oneidensis cytoplasm with HyPer-3 sensors and indicate that proper redox conditions in minimal growth medium are maintained by the concerted action of both well-known (periplasmic PgpD, cytoplasmic KatB and KatG1) and previously overlooked (cytoplasmic KatG2) peroxidases and catalases.

The Synergistic Mechanism of Photosynthesis and Antioxidant Metabolism between the Green and White Tissues of Ananas comosus var. bracteatus Chimeric Leaves.

Ananas comosus var. bracteatus (Ac. bracteatus) is a typical leaf-chimeric ornamental plant. The chimeric leaves are composed of central green photosynthetic tissue (GT) and marginal albino tissue (AT). The mosaic existence of GT and AT makes the chimeric leaves an ideal material for the study of the synergistic mechanism of photosynthesis and antioxidant metabolism. The daily changes in net photosynthetic rate (NPR) and stomatal conductance (SCT) of the leaves indicated the typical crassulacean acid metabolism (CAM) characteristic of Ac. bracteatus. Both the GT and AT of chimeric leaves fixed CO2 during the night and released CO2 from malic acid for photosynthesis during the daytime. The malic acid content and NADPH-ME activity of the AT during the night was significantly higher than that of GT, which suggests that the AT may work as a CO2 pool to store CO2 during the night and supply CO2 for photosynthesis in the GT during the daytime. Furthermore, the soluble sugar content (SSC) in the AT was significantly lower than that of GT, while the starch content (SC) of the AT was apparently higher than that of GT, indicating that AT was inefficient in photosynthesis but may function as a photosynthate sink to help the GT maintain high photosynthesis activity. Additionally, the AT maintained peroxide balance by enhancing the non-enzymatic antioxidant system and antioxidant enzyme system to avoid antioxidant damage. The enzyme activities of reductive ascorbic acid (AsA) and the glutathione (GSH) cycle (except DHAR) and superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) were enhanced, apparently to make the AT grow normally. This study indicates that, although the AT of the chimeric leaves was inefficient at photosynthesis because of the lack of chlorophyll, it can cooperate with the GT by working as a CO2 supplier and photosynthate store to enhance the photosynthetic ability of GT to help chimeric plants grow well. Additionally, the AT can avoid peroxide damage caused by the lack of chlorophyll by enhancing the activity of the antioxidant system. The AT plays an active role in the normal growth of the chimeric leaves.

Imaging of mtHyPer7, a Ratiometric Biosensor for Mitochondrial Peroxide, in Living Yeast Cells.

Mitochondrial dysfunction, or functional alteration, is found in many diseases and conditions, including neurodegenerative and musculoskeletal disorders, cancer, and normal aging. Here, an approach is described to assess mitochondrial function in living yeast cells at cellular and subcellular resolutions using a genetically encoded, minimally invasive, ratiometric biosensor. The biosensor, mitochondria-targeted HyPer7 (mtHyPer7), detects hydrogen peroxide (H2O2) in mitochondria. It consists of a mitochondrial signal sequence fused to a circularly permuted fluorescent protein and the H2O2-responsive domain of a bacterial OxyR protein. The biosensor is generated and integrated into the yeast genome using a CRISPR-Cas9 marker-free system, for more consistent expression compared to plasmid-borne constructs. mtHyPer7 is quantitatively targeted to mitochondria, has no detectable effect on yeast growth rate or mitochondrial morphology, and provides a quantitative readout for mitochondrial H2O2 under normal growth conditions and upon exposure to oxidative stress. This protocol explains how to optimize imaging conditions using a spinning-disk confocal microscope system and perform quantitative analysis using freely available software. These tools make it possible to collect rich spatiotemporal information on mitochondria both within cells and among cells in a population. Moreover, the workflow described here can be used to validate other biosensors.

The multifaceted nature of peroxiredoxins in chemical biology.

Peroxiredoxins (Prx), thiol-dependent peroxidases, were first identified as H2O2 detoxifiers, and more recently as H2O2 sensors, intermediates in redox-signaling pathways, metabolism modulators, and chaperones. The multifaceted nature of Prx is not only dependent on their peroxidase activity but also strongly associated with specific protein-protein interactions that are being identified, and where the Prx oligomerization dynamics plays a role. Their oxidation by a peroxide substrate forms a sulfenic acid that opens a route to channel the redox signal to diverse protein targets. Recent research underscores the importance of different Prx isoforms in the cellular processes behind disease development with potential therapeutic applications.

Structural evidence for intermediates during O2 formation in photosystem II.

In natural photosynthesis, the light-driven splitting of water into electrons, protons and molecular oxygen forms the first step of the solar-to-chemical energy conversion process. The reaction takes place in photosystem II, where the Mn4CaO5 cluster first stores four oxidizing equivalents, the S0 to S4 intermediate states in the Kok cycle, sequentially generated by photochemical charge separations in the reaction center and then catalyzes the O-O bond formation chemistry1-3. Here, we report room temperature snapshots by serial femtosecond X-ray crystallography to provide structural insights into the final reaction step of Kok's photosynthetic water oxidation cycle, the S3→[S4]→S0 transition where O2 is formed and Kok's water oxidation clock is reset. Our data reveal a complex sequence of events, which occur over micro- to milliseconds, comprising changes at the Mn4CaO5 cluster, its ligands and water pathways as well as controlled proton release through the hydrogen-bonding network of the Cl1 channel. Importantly, the extra O atom Ox, which was introduced as a bridging ligand between Ca and Mn1 during the S2→S3 transition4-6, disappears or relocates in parallel with Yz reduction starting at approximately 700 µs after the third flash. The onset of O2 evolution, as indicated by the shortening of the Mn1-Mn4 distance, occurs at around 1,200 µs, signifying the presence of a reduced intermediate, possibly a bound peroxide.

The potential effect of Moringa oleifera ethanolic leaf extract against oxidative stress, immune response disruption induced by abamectin exposure in Oreochromis niloticus.

Abamectin (ABM), a naturally fermented product of Streptomyces avermitilis, is applied to pest control in livestock and agriculture fields. The aim of the current study is to evaluate the protective effects of Moringa oleifera leaf ethanolic extract (MOE) on biochemical changes including oxidative stress indices, immune response marker, lipid profiles as well as mRNA expression of immune related genes, and abamectin (ABM, 5% EC) residue levels in Nile tilapia (Oreochromis niloticus) exposed to a sub-lethal concentration (0.5 µg/l) for 28 days. Disturbance in liver and kidney biomarkers was markedly increased in ABM-exposed fish compared to the control group. Malondialdehyde levels in the liver and brain tissues, as well as the activities of glutathione-s-transferase, superoxide dismutase, and glutathione peroxides, all increased significantly in ABM group. Additionally, ABM exposure increased the levels of interleukin 10 beta and growth factor gene expression. On the other hand, fish exposed to ABM had significantly lower serum alkaline phosphatase, creatinine, high-density lipoprotein, glutathione peroxides in brain, glutathione in liver and brain tissues, lysozyme activity, nitric oxide, immunoglobulin M, tumor necrosis factor, and interleukin 1 beta as compared to the control group. The recorded detrimental effects of ABM on tilapia have been overcome by the addition of MOE to the diet (1%) and ameliorating hepato-renal damage and enhancing antioxidant activity, innate immune responses, and upregulating the anti-inflammatory gene expression. Therefore, it could be concluded that MOE dietary supplementation at 1% could be used to counteract the oxidative stress, immune response disruption induced by abamectin exposure in Oreochromis niloticus, and reduce its accumulation in fish tissues.

Protein S-glutathionylation and sex dimorphic effects on hydrogen peroxide production by dihydroorotate dehydrogenase in liver mitochondria.

Dihydroorotate dehydrogenase (DHODH) oxidizes dihydroorotate to orotate for pyrimidine biosynthesis, donating electrons to the ubiquinone (UQ) pool of mitochondria. DHODH has a measurable rate for hydrogen peroxide (H2O2) production and thus contributes to cellular changes in redox tone. Protein S-glutathionylation serves as a negative feedback loop for the inhibition of H2O2 by several α-keto acid dehydrogenases and respiratory complexes in mitochondria, as well as ROS sources in liver cytoplasm. Here, we report this redox signaling mechanism also inhibits H2O2 production by DHODH in liver mitochondria isolated from male and female C57BL6N mice. We discovered that low amounts of the glutathionylation catalyst, disulfiram (50-500 nM), almost abolished H2O2 production by DHODH in mitochondria from male mice. Similar results were collected with diamide, however, higher doses (1000-5000 µM) were required to elicit this effect. Disulfiram and diamide also significantly suppressed H2O2 production by DHODH in female liver mitochondria. However, liver mitochondria from female mice were more resistant to disulfiram or diamide-mediated inhibition of H2O2 genesis when compared to samples from males. Analysis of the impact of disulfiram and diamide on DHODH activity revealed that both compounds inhibited the dehydrogenase directly, however the effect was less in female mice. Additionally, disulfiram and diamide impeded the use of dihydroorotate fueled oxidative phosphorylation in mitochondria from males and females, although samples collected from female rodents displayed more resistance to this inhibition. Taken together, our findings demonstrate H2O2 production by DHODH can be inhibited by glutathionylation and sex can impact this redox modification.

Tomato seed oil-enriched tomato juice: Effect of oil addition type and heat treatment on lycopene bioaccessibility and oxidative stability.

In this study, tomato seed oil conventional emulsion (7 µm) and nanoemulsion (0.146 µm) with desirable stability were prepared, then the effect of tomato seed oil addition (bulk and emulsified forms) and thermal treatment on properties of tomato juice was evaluated. Tomato juice without oil and heat treatment exhibited the lowest bioaccessibility of lycopene (17.8 %). Incorporation of oil and applying heat treatment significantly increased the extent of lipid digestion and bioaccessibility of lycopene. In this regard, the nanoemulsion had the highest bioaccessibility (44.85 %) compared to conventional emulsion (33.90 %) and bulk oil (27.11 %), due to the smaller oil droplets. The oxidative stability of oil in heat-treated tomato juice samples decreased during 28 days of storage at 4 °C, whereas the nanoemulsion exhibited the highest peroxide value (4.43 meq O2/kg of oil) compared to conventional emulsion and bulk oil (3.91 and 3.49 meq O2/kg of oil, respectively) at the end of the period.

Metal binding and oligomerization properties of FurC (PerR) from Anabaena sp. PCC7120: an additional layer of regulation?

Metal and redox homeostasis in cyanobacteria is tightly controlled to preserve the photosynthetic machinery from mismetallation and minimize cell damage. This control is mainly taken by FUR (ferric uptake regulation) proteins. FurC works as the PerR (peroxide response) paralog in Anabaena sp. PCC7120. Despite its importance, this regulator remained poorly characterized. Although FurC lacks the typical CXXC motifs present in FUR proteins, it contains a tightly bound zinc per subunit. FurC: Zn stoichiometrically binds zinc and manganese in a second site, manganese being more efficient in the binding of FurC: Zn to its DNA target PprxA. Oligomerization analyses of FurC: Zn evidence the occurrence of different aggregates ranging from dimers to octamers. Notably, intermolecular disulfide bonds are not involved in FurC: Zn dimerization, dimer being the most reduced form of the protein. Oligomerization of dimers occurs upon oxidation of thiols by H2O2 or diamide and can be reversed by 1,4-Dithiothreitol (DTT). Irreversible inactivation of the regulator occurs by metal catalyzed oxidation promoted by ferrous iron. However, inactivation upon oxidation with H2O2 in the absence of iron was reverted by addition of DTT. Comparison of models for FurC: Zn dimers and tetramers obtained using AlphaFold Colab and SWISS-MODEL allowed to infer the residues forming both metal-binding sites and to propose the involvement of Cys86 in reversible tetramer formation. Our results decipher the existence of two levels of inactivation of FurC: Zn of Anabaena sp. PCC7120, a reversible one through disulfide-formed FurC: Zn tetramers and the irreversible metal catalyzed oxidation. This additional reversible regulation may be specific of cyanobacteria.

Selenoprotein P - Selenium transport protein, enzyme and biomarker of selenium status.

The habitual intake of selenium (Se) varies strongly around the world, and many people are at risk of inadequate supply and health risks from Se deficiency. Within the human organism, efficient transport mechanisms ensure that organs with a high demand and relevance for reproduction and survival are preferentially supplied. To this end, selenoprotein P (SELENOP) is synthesized in the liver and mediates Se transport to essential tissues such as the endocrine glands and the brain, where the "SELENOP cycle" maintains a privileged Se status. Mouse models indicate that SELENOP is not essential for life, as supplemental Se supply was capable of preventing the development of severe symptoms. However, knockout mice died under limiting supply, arguing for an essential role of SELENOP in Se deficiency. Many clinical studies support this notion, pointing to close links between health risks and low SELENOP levels. Accordingly, circulating SELENOP concentrations serve as a functional biomarker of Se supply, at least until a saturated status is achieved and SELENOP levels reach a plateau. Upon toxic intake, a further increase in SELENOP is observed, i.e., SELENOP provides information about possible selenosis. The SELENOP transcripts predict an insertion of ten selenocysteine residues. However, the decoding is imperfect, and not all these positions are ultimately occupied by selenocysteine. In addition to the selenocysteine residues near the C-terminus, one selenocysteine resides central within an enzyme-like environment. SELENOP proved capable of catalyzing peroxide degradation in vitro and protecting e.g. LDL particles from oxidation. An enzymatic activity in the intact organism is unclear, but an increasing number of clinical studies provides evidence for a direct involvement of SELENOP-dependent Se transport as an important and modifiable risk factor of disease. This interaction is particularly strong for cardiovascular and critical disease including COVID-19, cancer at various sites and autoimmune thyroiditis. This review briefly highlights the links between the growing knowledge of Se in health and disease over the last 50 years and the specific advances that have been made in our understanding of the physiological and clinical contribution of SELENOP to the current picture.

Protective Effect of SeMet on Liver Injury Induced by Ochratoxin A in Rabbits.

Ochratoxin A (OTA) is second only to aflatoxin in toxicity among mycotoxins. Recent studies have shown that selenomethionine (SeMet) has a protective effect on mycotoxin-induced toxicity. The purpose of this study was to investigate the protective effect and mechanism of SeMet on OTA-induced liver injury in rabbits. Sixty 35-day-old rabbits with similar body weight were randomly divided into five groups: control group, OTA group (0.2 mg/kg OTA), OTA + 0.2 mg/kg SeMet group, OTA + 0.4 mg/kg SeMet group and OTA + 0.6 mg/kg SeMet group. Rabbits were fed different doses of the SeMet diet for 21 d, and OTA was administered for one week from day 15 (the control group was provided the same dose of NaHCO3 solution). The results showed that 0.4 mg/kg SeMet could significantly improve the liver injury induced by OTA poisoning. SeMet supplementation can improve the changes in physiological blood indexes caused by OTA poisoning in rabbits and alleviate pathological damage to the rabbit liver. SeMet also increased the activities of SOD, GSH-Px and T-AOC and significantly decreased the contents of ROS, MDA, IL-1ß, IL-6 and TNF-α, effectively alleviating the oxidative stress and inflammatory response caused by OTA poisoning. In addition, OTA poisoning inhibits Nrf2 and HO-1 levels, ultimately leading to peroxide reaction, while SeMet activates the Nrf2 signaling pathway and enhances the expression of the HO-1 downstream Nrf2 gene. These results suggest that Se protects the liver from OTA-induced hepatotoxicity by regulating Nrf2/HO-1 expression.

The Transcriptional Regulator SpxA1 Influences the Morphology and Virulence of Listeria monocytogenes.

Listeria monocytogenes is a Gram-positive facultative anaerobe and an excellent model pathogen for investigating regulatory changes that occur during infection of a mammalian host. SpxA1 is a widely conserved transcriptional regulator that induces expression of peroxide-detoxifying genes in L. monocytogenes and is thus required for aerobic growth. SpxA1 is also required for L. monocytogenes virulence, although the SpxA1-dependent genes important in this context remain to be identified. Here, we sought to investigate the role of SpxA1 in a tissue culture model of infection and made the surprising discovery that ΔspxA1 cells are dramatically elongated during growth in the host cytosol. Quantitative microscopy revealed that ΔspxA1 cells also form elongated filaments extracellularly during early exponential phase in rich medium. Scanning and transmission electron microscopy analysis found that the likely cause of this morphological phenotype is aberrantly placed division septa localized outside cell midpoints. Quantitative mass spectrometry of whole-cell lysates identified SpxA1-dependent changes in protein abundance, including a significant number of motility and flagellar proteins that were depleted in the ΔspxA1 mutant. Accordingly, we found that both the filamentation and the lack of motility contributed to decreased phagocytosis of ΔspxA1 cells by macrophages. Overall, we identify a novel role for SpxA1 in regulating cell elongation and motility, both of which impact L. monocytogenes virulence.