Atox1 protects hippocampal neurons after traumatic brain injury via DJ-1 mediated anti-oxidative stress and mitophagy.

Regulation of the oxidative stress response is crucial for the management and prognosis of traumatic brain injury (TBI). The copper chaperone Antioxidant 1 (Atox1) plays a crucial role in regulating intracellular copper ion balance and impacting the antioxidant capacity of mitochondria, as well as the oxidative stress state of cells. However, it remains unknown whether Atox1 is involved in modulating oxidative stress following TBI. Here, we investigated the regulatory role of Atox1 in oxidative stress on neurons both in vivo and in vitro, and elucidated the underlying mechanism through culturing hippocampal HT-22 cells with Atox1 mutation. The expression of Atox1 was significantly diminished following TBI, while mice with overexpressed Atox1 exhibited a more preserved hippocampal structure and reduced levels of oxidative stress post-TBI. Furthermore, the mice displayed notable impairments in learning and memory functions after TBI, which were ameliorated by the overexpression of Atox1. In the stretch injury model of HT-22 cells, overexpression of Atox1 mitigated oxidative stress by preserving the normal morphology and network connectivity of mitochondria, as well as facilitating the elimination of damaged mitochondria. Mechanistically, co-immunoprecipitation and mass spectrometry revealed the binding of Atox1 to DJ-1. Knockdown of DJ-1 in HT-22 cells significantly impaired the antioxidant capacity of Atox1. Mutations in the copper-binding motif or sequestration of free copper led to a substantial decrease in the interaction between Atox1 and DJ-1, with overexpression of DJ-1 failing to restore the antioxidant capacity of Atox1 mutants. The findings suggest that DJ-1 mediates the ability of Atox1 to withstand oxidative stress. And targeting Atox1 could be a potential therapeutic approach for addressing post-traumatic neurological dysfunction.

Meningioma achieves malignancy and erastin-induced ferroptosis resistance through FOXM1-AURKA-NRF2 axis.

The oncogene Aurora kinase A (AURKA) has been implicated in various tumor, yet its role in meningioma remains unexplored. Recent studies have suggested a potential link between AURKA and ferroptosis, although the underlying mechanisms are unclear. This study presented evidence of AURKA upregulation in high grade meningioma and its ability to enhance malignant characteristics. We identified AURKA as a suppressor of erastin-induced ferroptosis in meningioma. Mechanistically, AURKA directly interacted with and phosphorylated kelch-like ECH-associated protein 1 (KEAP1), thereby activating nuclear factor erythroid 2 related factor 2 (NFE2L2/NRF2) and target genes transcription. Additionally, forkhead box protein M1 (FOXM1) facilitated the transcription of AURKA. Suppression of AURKA, in conjunction with erastin, yields significant enhancements in the prognosis of a murine model of meningioma. Our study elucidates an unidentified mechanism by which AURKA governs ferroptosis, and strongly suggests that the combination of AURKA inhibition and ferroptosis-inducing agents could potentially provide therapeutic benefits for meningioma treatment.

Endophytic bacterial communities in ungerminated and germinated seeds of commercial vegetables.

Chile is a prominent seed exporter globally, but the seed microbiome of vegetables (46% of seeds) and its role in the early stages of plant growth have remained largely unexplored. Here, we employed DNA metabarcoding analysis to investigate the composition and putative functions of endophytic bacterial communities in ungerminated and germinated seeds of the commercial vegetables Apiaceae (parsley and carrot), Asteraceae (lettuce), Brassicaceae (cabbage and broccoli), and Solanaceae (tomato). Bacterial quantification showed 104 to 108 copies of the 16S rRNA gene per gram of ungerminated and germinated seeds. Alpha diversity analysis (e.g., Chao1, Shannon, and Simpson indices) did not indicate significant differences (Kruskal-Wallis test) between ungerminated and germinated seeds, except for Solanaceae. However, beta diversity (PCoA) analysis showed distinctions (Adonis test) between ungerminated and germinated seeds, except Apiaceae. Pseudomonadota and Bacillota were identified as the dominant and specialist taxa in both ungerminated and germinated seed samples. Chemoheterotrophy and fermentation were predicted as the main microbial functional groups in the endophytic bacterial community. Notably, a considerable number of the 143 isolated endophytic strains displayed plant growth-promoting traits (10 to 64%) and biocontrol activity (74% to 82%) against plant pathogens (Xanthomonas and Pseudomonas). This study revealed the high variability in the abundance, diversity, composition, and functionality of endophytic bacteria between ungerminated and germinated seeds in globally commercialized vegetables. Furthermore, potential beneficial endophytic bacteria contained in their seed microbiomes that may contribute to the microbiome of the early stages, development, growth and progeny of vegetables were found.

Structure and Functional Properties of Bacterial Communities in Surface Sediments of the Recently Declared Nutrient-Saturated Lake Villarrica in Southern Chile.

Lake Villarrica, one of Chile's main freshwater water bodies, was recently declared a nutrient-saturated lake due to increased phosphorus (P) and nitrogen (N) levels. Although a decontamination plan based on environmental parameters is being established, it does not consider microbial parameters. Here, we conducted high-throughput DNA sequencing and quantitative polymerase chain reaction (qPCR) analyses to reveal the structure and functional properties of bacterial communities in surface sediments collected from sites with contrasting anthropogenic pressures in Lake Villarrica. Alpha diversity revealed an elevated bacterial richness and diversity in the more anthropogenized sediments. The phylum Proteobacteria, Bacteroidetes, Acidobacteria, and Actinobacteria dominated the community. The principal coordinate analysis (PCoA) and redundancy analysis (RDA) showed significant differences in bacterial communities of sampling sites. Predicted functional analysis showed that N cycling functions (e.g., nitrification and denitrification) were significant. The microbial co-occurrence networks analysis suggested Chitinophagaceae, Caldilineaceae, Planctomycetaceae, and Phycisphaerae families as keystone taxa. Bacterial functional genes related to P (phoC, phoD, and phoX) and N (nifH and nosZ) cycling were detected in all samples by qPCR. In addition, an RDA related to N and P cycling revealed that physicochemical properties and functional genes were positively correlated with several nitrite-oxidizing, ammonia-oxidizing, and N-fixing bacterial genera. Finally, denitrifying gene (nosZ) was the most significant factor influencing the topological characteristics of co-occurrence networks and bacterial interactions. Our results represent one of a few approaches to elucidate the structure and role of bacterial communities in Chilean lake sediments, which might be helpful in conservation and decontamination plans.

Quality Attributes and Dielectric Properties of Sea Buckthorn Berries under Differing Freezing Regimes and Their Interrelationships.

Fruit quality attributes interrelate with their dielectric properties, but such interrelationships in sea buckthorn berries under differing freezing regimes remain uninvestigated. Sea buckthorn (Hipophae rhamnoides L., cv. Shenqiuhong) berries were frozen at different temperatures (-13, -30, -35 and -40 °C) and stored for different periods (15, 30, 45, 60, 75 and 90 d). Seven quality attributes and nine dielectric parameters were measured to evaluate the effect of different frozen storage regimes on those attributes and parameters. The results showed that shorter time and lower temperature contributed to the preservation of berries quality. The dielectric parameters values increased with decreasing temperature and with the increase of freezing duration. The quality prediction models were established by the principal component analysis of the dielectric properties at characteristic frequency. The results are expected to provide a way to evaluate quality of frozen sea buckthorn berries by dielectric properties.

Nuclear receptor coactivator 4-mediated ferritinophagy contributes to cerebral ischemia-induced ferroptosis in ischemic stroke.

Ischemic stroke poses a significant health risk due to its high rate of disability and mortality. To address this problem, several therapeutic approaches have been proposed, including interruption targeting programmed cell death (PCD). Ferroptosis is a newly defined PCD characterized by iron-dependent accumulation of lipid peroxidation, and is becoming a promising target for treating numerous diseases. To explore the underlying mechanisms of the initiation and execution of ferroptosis in ischemic stroke, we established stroke models in vivo and in vitro simulating ischemia/reperfusion (I/R) neuronal injury. Different from previous reports on stroke, we tested ferroptosis by measuring the levels of core proteins, such as ACSL4, 15-LOX2, Ferritin and GPX4. In addition, I/R injury induces excessive degradation of ferritin via the autophagy pathway and subsequent increase of free iron in neurons. This phenomenon has recently been termed ferritinophagy and reported to be regulated by nuclear receptor coactivator 4 (NCOA4) in some cell lines. Increased NCOA4 in cytoplasm was detected in our study and then silenced by shRNA to investigate its function. Both in vivo and in vitro, NCOA4 deletion notably abrogated ferritinophagy caused by I/R injury and thus inhibited ferroptosis. Furthermore, we found that NCOA4 was upregulated by ubiquitin specific peptidase 14 (USP14) via a deubiquitination process in damaged neurons, and we found evidence of pharmacological inhibition of USP14 effectively reducing NCOA4 levels to protect neurons from ferritinophagy-mediated ferroptosis. These findings suggest a novel and effective target for treating ischemic stroke.

Serum Iron and Ferritin Levels Are Correlated with Complement C3.

Iron is one of the most important trace elements in the body, and its homeostasis is essential to the normal function of the immune system. Complement component C3, which is the converging of three main pathways of complement system activation, plays a key role in the innate immunity. However, the relationship between iron homeostasis and complement C3 remains unknown. The aim of our study was to analyze the relationship between serum iron and ferritin level and complement C3 and C4. A total of 590 healthy individuals were recruited in our study. Higher serum complement C3 level (p < 0.001) was found in individuals with higher serum ferritin level (> 104.0 µg/L). Moreover, serum iron level and serum ferritin level were positively correlated with complement C3 (r = 0.133, p = 0.001; r = 0.221, p < 0.001) and complement C4 (r = 0.117, p = 0.004; r = 0.123, p = 0.003). The linear regression analysis displayed that both serum iron level and serum ferritin level were linearly correlated with serum complement C3 level (adjusted beta: 2.382, 95% CI: 0.841-3.923; adjusted beta: 42.911, 95% CI: 29.070-56.751). To explore the relationship between iron homeostasis and complement C3 further, the serum samples from C3-/- mice and the wild-type (WT) control mice were obtained. Significantly lower serum iron level and higher ferritin level were found in C3-/- mice than those in WT mice (p < 0.001; p < 0.001), indicating that complement C3 might influence iron distribution and utilization. Overall, these data suggested that serum iron and ferritin levels were correlated with complement C3. The deficiency of complement C3 may disrupt the regular iron metabolism in the body.

The interference of nonylphenol with bacterial cell-to-cell communication.

The interference of nonylphenol (NP) with humans and animals, especially in hormone systems, has been well-studied. There is rarely any record of its effect on bacteria, which dominate in various environments. In our study, we employed Pseudomonas aeruginosa PAO1 as a model microorganism and took its common lifestyle biofilm, mainly regulated by quorum sensing (QS), as a cut-in point to investigate the effect of NP (1, 5, 10 mg L-1) on bacteria. The results showed that more than 5 mg L-1 of NP did interfere with biofilm formation and affected bacterial QS. In detail, the LasI/R circuit, but not the RhlI/R circuit, was considerably obstructed. The decrease in lasI and lasR expression resulted in a significant reduction in N-3-oxo-dodecanoyl homoserine lactone (3OC12-HSL) signals and the downstream production of elastases. Docking results indicated the binding of NP with LasR protein, simulating the binding of 3OC12-HSL with LasR protein, which explained the obstruction of the LasIR circuit. We concluded that NP competed with 3OC12-HSL and blocked 3OC12-HSL binding with the LasR protein, resulting in a direct interference in bacterial biofilm formation. This is the first report of NP interference with bacterial signaling, which is not only helpful to understand the effect of NP on various ecosystems, but is also beneficial to enrich our knowledge of inter-kingdom communication.

Mixture of different Pseudomonas aeruginosa SD-1 strains in the efficient bioaugmentation for synthetic livestock wastewater treatment.

Strains selection for inoculation is the key to the successful construction of a bioaugmentation system, a promising strategy for specific pollutant removal. Pseudomonas aeruginosa SD-1 wild-type (WT) strain exhibited high capacity for biofilm formation but low efficiency for nitrate (NO3-) removal. Meanwhile, quorum sensing deficient strain ΔlasR showed excellent efficiency for NO3- removal but poor capability for colonization in activated sludge. The opposite effect of biofilm formation and NO3- removal exist in WT or ΔlasR, which limits the construction of bioaugmentation system of strain SD-1 and its application. To solve this issue, a mixture of WT and ΔlasR (v/v = 1:1) was used to construct a bioaugmentation system. Compared with the inoculation of WT or ΔlasR alone, the mixed inoculation not only was beneficial for activated sludge development but also for pollutant removal. The indicators for activated sludge including the abundance of P. aeruginosa, the sludge volume index and the average particle size in mixed inoculated reactors were close to those of reactors with single and repeated inoculation of WT. The effluent of chemical oxygen demand (COD) and NO3--N were stable at 3.9-22.6 mg L-1 and 0-5.53 mg L-1 after d 3, respectively. This study presents a detailed case on the ecological tradeoff of colonization and pollutant removal of inoculated strains during bioaugmentation. The results provide information on the appropriate conditions for application of P. aeruginosa SD-1 for livestock wastewater treatment and further enrich our ecological understanding of bioaugmentation.