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BackgroundGastric cancer (GC) poses a global health challenge due to its widespread prevalence and unfavorable prognosis. Although immunotherapy has shown promise in clinical settings, its efficacy remains limited to a minority of GC patients. Manganese, recognized for its role in the body’s anti-tumor immune response, has the potential to enhance the effectiveness of tumor treatment when combined with immune checkpoint inhibitors.MethodsGene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases was utilized to obtain transcriptome information and clinical data for GC. Unsupervised clustering was employed to stratify samples into distinct subtypes. Manganese metabolism- and immune-related genes (MIRGs) were identified in GC by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis. We conducted gene set variation analysis, and assessed the immune landscape, drug sensitivity, immunotherapy efficacy, and somatic mutations. The underlying role of NPR3 in GC was further analyzed in the single-cell RNA sequencing data and cellular experiments.ResultsGC patients were classified into four subtypes characterized by significantly different prognoses and tumor microenvironments. Thirteen genes were identified and established as MIRGs, demonstrating exceptional predictive effectiveness in GC patients. Distinct enrichment patterns of molecular functions and pathways were observed among various risk subgroups. Immune infiltration analysis revealed a significantly greater abundance of macrophages and monocytes in the high-risk group. Drug sensitivity analysis identified effective drugs for patients, while patients in the low-risk group could potentially benefit from immunotherapy. NPR3 expression was significantly downregulated in GC tissues. Single-cell RNA sequencing analysis indicated that the expression of NPR3 was distributed in endothelial cells. Cellular experiments demonstrated that NPR3 facilitated the proliferation of GC cells.ConclusionThis is the first study to utilize manganese metabolism- and immune-related genes to identify the prognostic MIRGs for GC. The MIRGs not only reliably predicted the clinical outcome of GC patients but also hold the potential to guide future immunotherapy interventions for these patients.

Chlamydia protein associating with death domains ( Ct CADD) is involved in the biosynthesis of p -aminobenzoic acid (pABA) for integration into folate, a critical cofactor that is required for pathogenic survival. CADD activates dioxygen and utilizes its own tyrosine and lysine as synthons to furnish the carboxylate, carbon backbone, and amine group of pABA in a complex multistep mechanism. Unlike other members of the heme oxygenase-like dimetal oxidase (HDO) superfamily that typically house an Fe 2 cofactor, previous activity studies have shown that Ct CADD likely uses a heterobimetallic Fe/Mn center. The structure of the Fe 2+ /Mn 2+ cofactor and how the conserved HDO scaffold mediates metal selectivity have remained enigmatic. Adopting an in crystallo metalation approach, Ct CADD was solved in the apo, Fe 2+ 2 , Mn 2+ 2 , and catalytically active Fe 2+ /Mn 2+ forms to identify the probable site for Mn binding. The analysis of Ct CADD active-site variants further reinforces the importance of the secondary coordination sphere on cofactor preference for competent pABA formation. Rapid kinetic optical and electron paramagnetic resonance (EPR) studies show that the heterobimetallic cofactor selectively reacts with dioxygen and likely initiates pABA assembly through the formation of a transient tyrosine radical intermediate and a resultant heterobimetallic Mn 3+ /Fe 3+ cluster.

We investigated the renal function of the brackish water clam, Ruditapes philippinarum, employing magnetic resonance imaging (MRI). The R. philippinarum kidney consists of two renal tubules, a glandular (GT) and a saccular (ST) tubule. After exposure to seawater containing manganese ion (Mn2+) at 20°C, the intensity of the T1-weighted MRI and longitudinal relaxation rates (1/T1=R1) of the kidney were increased. In the ST, haemolymph containing Mn2+ entered directly from the auricle, and the Mn2+ concentration ([Mn2+]) increased in the initial part of the ST. Thereafter, [Mn2+] was almost constant until the posterior end of the kidney. The GT received haemolymph from the pedal sinus via the visceral sinus. The GT runs parallel inside the ST, and [Mn2+] increased progressively until it merged with the ST. In a range of seawater with [Mn2+] from 1 to 30 µmol l-1, the [Mn2+] increased 12-fold in the posterior part of the ST, compared with the ambient [Mn2+]. Based on these results, the epithelium of the initial part of the ST reabsorbs water from luminal fluid, building up a higher osmotic pressure. Using this osmotic gradient, hypertonic water is reabsorbed via the epithelium of the GT to the ST, and then transferred to the haemolymph via the epithelium of the ST. Excess water is excreted as urine. This model was supported by the increases in [Mn2+] in the ST when the clams were exposed to seawater containing Mn2+ at salinity from 26.0 to 36.0‰, showing that the parallel-current system works in hypotonic seawater., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

The application of manganese-oxidizing bacteria (MnOB) to produce manganese oxides (MnOx) has been widely studied, but often overlooking the concurrent formation of MnCO 3 . In this study, we found Ca 2+ plays a crucial role in controlling Mn(II) removal in the bacterium Aurantimonas sp. HBX-1. Under conditions with 6.8 mM Ca 2+ and without adding Ca 2+ , 100 μM Mn(II) was removed by 96.96 % and 38.28 % within 8 days, respectively. X-ray photoelectron spectroscopy (XPS) showed that adding Ca 2+ increased the average oxidation state (AOS) of the solid products from 2.05 to 2.37. X-ray absorption fine structure (XAFS) analysis revealed the product proportions as follows: under Ca 2+ -supplemented condition, the ratio of MnOx (1 < x ≤ 2) to MnCO₃ was 52 % to 28.1 %, while under Ca 2+ -free condition, the ratio shifted to 4.6 % for MnOx (1 < x ≤ 2) and 55.2 % for MnCO₃. Urease activity assay and proteomic analysis confirmed the expression of urease and carbonic anhydrase, leading to the formation of MnCO 3 . Additionally, animal heme peroxidase (AHP) in strain HBX-1 was found to be responsible for Mn(II) oxidation through superoxide production, with Ca 2+ addition promoting its expression level. Given the widespread presence of Ca 2+ in wastewater, its potential impact on the biogeochemical Mn(II) cycle driven by bacteria should be reconsidered., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

For over a century, the filamentous Ascomycete fungus Aspergillus niger has played a pivotal role in the industrial production of citric acid. A critical fermentation parameter that sustains high-yield citric acid accumulation is the suboptimal concentration of manganese(II) ions in the culture broth at the early stages of the process. However, the requirement for this deficiency has not been investigated on a functional genomics level. In this study, we compared the transcriptome of the citric acid hyper-producer A. niger NRRL2270 strain grown under citric acid-producing conditions in 6-L scale bioreactors at Mn 2+ ion-deficient (5 ppb) and Mn 2+ ion-sufficient (100 ppb) conditions at three early time points of cultivation. Of the 11,846 genes in the genome, 963 genes (8.1% of the total) were identified as significantly differentially expressed under these conditions. Disproportionately high number of differentially regulated genes encode predicted extracellular and membrane proteins. The most abundant gene group that was upregulated in Mn 2+ ion deficiency condition encodes enzymes acting on polysaccharides. In contrast, six clusters of genes encoding secondary metabolites showed downregulation under manganese deficiency. Mn 2+ deficiency also triggers upregulation of the cexA gene, which encodes the citrate exporter. We provide functional evidence that the upregulation of cexA is caused by the intracellular accumulation of citrate or acetyl-CoA and is a major factor in triggering citrate overflow., Importance: Citric acid is produced on industrial scale by batch fermentation of the filamentous fungus Aspergillus niger . High-yield citric acid production requires a low (<5 ppb) manganese(II) ion concentration in the culture broth. However, the requirement for this deficiency has not been investigated on a functional genomics level. Here, we compared the transcriptome of a citric acid hyper-producer A. niger strain grown under citric acid-producing conditions in 6-L scale bioreactors at Mn 2+ ion-deficient (5 ppb) and Mn 2+ ion-sufficient (100 ppb) conditions at three early time points of cultivation. We observed that Mn 2+ deficiency triggers an upregulation of the citrate exporter gene cexA and provides functional evidence that this event is responsible for citrate overflow. In addition to the industrial relevance, this is the first study that examined the role of Mn 2+ ion deficiency in a heterotrophic eukaryotic cell on a genome-wide scale., Competing Interests: The authors declare no conflict of interest.

Science is challenging because we do not know what we do not know. Commercial chemicals are often marketed with >99% purity, but 0.5-1% impurity can impact results and cloud data interpretation. We recently developed an assay for farnesol and aromatic fusel alcohols from Candida albicans . During proof-of-concept experiments using RPMI-1640 growth media, the buffering compound was switched from MOPS obtained from Acros Organics to MOPS obtained from Sigma-Aldrich, both labeled 99% + purity. We observed a twofold decrease in growth, along with a three- to fivefold increase in farnesol production per cell upon the switch. ICP-MS showed that trace Mn(II) was present in Acros MOPS but absent in Sigma MOPS. Optimal growth was achieved by the addition of Mn(II), Zn(II), and Fe(II). We established upper and lower limits for Fe(II), Zn(II), Cu(II), and Mn(II) that allowed similar growth and then assessed 16 different mineral combinations in RPMI-1640 base media. The results show an increased production of farnesol and the aromatic fusel alcohols when Zn(II) is abundant, and a further increase in the aromatic fusel alcohols when both Fe(II) and Zn(II) are abundant. Finally, antifungal susceptibility testing displayed no significant difference between RPMI/MOPS with and without mineral supplementation. Supplemental Mn(II) was most needed for cell growth, while supplemental Zn(II) was most needed for the production of farnesol and the aromatic fusel alcohols. To avoid these artifacts due to metal contamination, we now use a modified RPMI supplemented with 1 mg/ L of Cu(II), Zn(II), Mn(II), and Fe(II)., Importance: The dimorphic fungus Candida albicans is a major opportunistic pathogen of humans. RPMI-1640 is a chemically defined growth medium commonly used with C. albicans . We identified over 32,000 publications with keywords RPMI and C. albicans . Additionally, Antifungal Susceptibility Testing (AFST) protocols in the United States (CLSI) and Europe (EUCAST) utilize RPMI as a base media to assess drug efficacy against clinical fungal isolates. RPMI contains many nutrients but no added trace metals. We found that the growth characteristics with RPMI were dependent on which MOPS buffer was chosen and the contamination of that buffer by trace levels of Mn(II) and Zn(II). Added Mn(II) was most needed for cell growth while added Zn(II) was most needed for secretion of farnesol and other signaling molecules., Competing Interests: The authors declare no conflict of interest.

A novel nitrate-dependent manganese (Mn) redox strain was isolated and identified as Dechloromonas sp.YZ8 in this study. The growth conditions of strain YZ8 were optimized by kinetic experiments. The nitrate (NO 3 - -N) removal efficiency was 100.0 % at 16 h at C/N of 2.0, pH of 7.0, and Mn(II) or Mn(IV) addition of 10.0 or 500.0 mg L -1 , along with an excellent Mn redox capacity. Transmission electron microscopy supported the Mn redox process inside and outside the cells of strain YZ8. When strain YZ8 was exposed to different concentrations of copper ion (Cu(II)), it turned out that moderate amounts of Cu(II) increased microbial activity and metabolic activities. Moreover, it was discovered that the appropriate amount of Cu(II) promoted the conversion of Mn(IV) and Mn(II) to Mn(III) and improved electron transfer capacity in the Mn redox system, especially the Mn redox process dominated by Mn(IV) reduction. Then, δ-MnO 2 and bio-manganese oxides (BMO) produced during the reaction process have strong adsorption of Cu(II). The surface valence changes of δ-MnO 2 before and after the reaction and the production of BMO, Mn(III)-rich intermediate black manganese ore (Mn 3 O 4 ), and Mn secondary minerals together confirmed the Mn redox pathway. The study provided new insights into the promotion mechanism and immobilization effects of redox-coupled denitrification of Mn in groundwater under Cu(II) stress., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cellular levels of the essential micronutrient manganese (Mn) need to be carefully balanced within narrow borders. In cyanobacteria, a sufficient Mn supply is critical for ensuring the function of the oxygen-evolving complex as the central part of the photosynthetic machinery. However, Mn accumulation is fatal for the cells. The reason for the observed cytotoxicity is unclear. To understand the causality behind Mn toxicity in cyanobacteria, we investigated the impact of excess Mn on physiology and global gene expression in the model organism Synechocystis sp. PCC 6803. We compared the response of the WT and the knock-out mutant in the Mn e x porter (Mnx), ∆ mnx , which is disabled in the export of surplus Mn and thus functions as a model for toxic Mn overaccumulation. While growth and pigment accumulation in ∆ mnx were severely impaired 24 h after the addition of tenfold Mn, the WT was not affected and thus mounted an adequate transcriptional response. RNA-seq data analysis revealed that the Mn stress transcriptomes partly resembled an iron limitation transcriptome. However, the expression of iron limitation signature genes isiABDC was not affected by the Mn treatment, indicating that Mn excess is not accompanied by iron limitation in Synechocystis . We suggest that the ferric uptake regulator, Fur, gets partially mismetallated under Mn excess conditions and thus interferes with an iron-dependent transcriptional response. To encounter mismetallation and other Mn-dependent problems on a protein level, the cells invest in transcripts of ribosomes, proteases and chaperones. In the case of the ∆ mnx mutant, the consequences of the disability to export excess Mn from the cytosol manifest in additionally impaired energy metabolism and oxidative stress transcriptomes with a fatal outcome. This study emphasizes the central importance of Mn homeostasis and the transporter Mnx's role in restoring and holding it.

The tea plants cultivated in acidic soils are vulnerable to excessive manganese (Mn), which increases the risk of Mn 2+ toxicity to physiology and development. Mn-cation diffusion facilitator (CDF) family genes have been implicated in regulating Mn homeostasis and tolerance. However, the mechanism of Mn tolerance of tea plants in acidic environments is still unknown. In this study, we initially examined the phenotypic characteristics and Mn contents variability in different tissues of tea plants under various Mn concentration at pH 5 and 4. We observed that tea plants exhibited remarkably high Mn tolerance at pH 4, with Mn accumulation notably elevated in the aboveground tissues under pH 4 condition after 28-day treatment. We found the expression levels of Mn-CDF genes, had different subcellular localization, were tissue-specific and significantly induced by high Mn concentrations at pH 4 condition. Furthermore, the yeast complementation assays indicated that the heterologous expression of Mn-CDF genes restored the growth of a Mn 2+ sensitive yeast strain, Δpmr1. Taken together, these results suggest that Mn-CDF family genes function as Mn transporters to participate in Mn tolerance in acidic environments. This study provides reference for further study on the mechanism of maintaining Mn homeostasis in tea plants under soil acidification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The rate of photosynthesis and, thus, CO 2 fixation, is limited by the rate of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). Not only does Rubisco have a relatively low catalytic rate, but it also is promiscuous regarding the metal identity in the active site of the large subunit. In Nature, Rubisco binds either Mg(II) or Mn(II), depending on the chloroplastic ratio of these metal ions; most studies performed with Rubisco have focused on Mg-bound Rubisco. Herein, we report the first crystal structure of a Mn-bound Rubisco, and we compare its structural properties to those of its Mg-bound analogues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The objective of this study was to determine how different sources of Zn, Mn, and Cu in the feed without and with phytase affect prececal myo-inositol hexakisphosphate (InsP 6 ) breakdown to myo-inositol (MI), prececal P digestibility, bone mineralization, and expression of mineral transporters in the jejunum of broiler chickens. A total of 896 male broiler chicks (Cobb 500) were distributed to 7 diets with 8 replicate pens (16 birds per floor pen). Experimental diets were fed from day 0 to 28. Diets were without or with phytase supplementation (0 or 750 FTU/kg) and were supplemented with three different trace mineral sources (TMS: sulfates, oxides, or chelates) containing 100 mg/kg Zn, 100 mg/kg Mn, and 125 mg/kg Cu. Prececal InsP 6 disappearance and P digestibility were affected by interaction (phytase × TMS: P ≤ 0.010). In diets without phytase supplementation, prececal InsP 6 disappearance and P digestibility were greater (P ≤ 0.001) in birds fed chelated minerals than in birds fed sulfates or oxides. However, no differences were observed between TMS in diets with phytase supplementation. Ileal MI concentration was increased by exogenous phytase but differed depending on TMS (phytase × TMS: P ≤ 0.050). Tibia ash concentration as well as Zn and Mn concentration in tibia ash were increased by phytase supplementation (P < 0.010), but the Cu concentration in tibia ash was not (P > 0.050). Gene expression of the assayed mineral transporters in the jejunum was not affected by diet (P > 0.050), except for Zn transporter 5 (phytase × TMS: P = 0.024). In conclusion, the tested TMS had minor effects on endogenous phytate degradation in the digestive tract of broiler chickens. However, in phytase-supplemented diets, the choice of TMS was not relevant to phytate degradation under the conditions of this study., (© 2024. The Author(s).)

Electrolytic manganese slag (EMR) is a solid waste generated in the manganese hydrometallurgy process. It not only takes up significant land space but also contains Mn 2+ , which can lead to environmental contamination. There is a need for research on the treatment and utilization of EMR. Improved EMR substrate for Pennisetum sinese Roxb growth was determined in pot planting experiments. The study tested the effects of leaching solution, microorganisms, leaf cell structures, and growth data. Results indicated a substrate of 45% EMR, 40% phosphogypsum, 5% Hericium erinaceus fungi residue, 5% quicklime, and 5% dolomite sand significantly increased the available phosphorus content (135.54 ± 2.88 μg·g -1 ) by 17.95 times, compared to pure soil, and enhanced the relative abundance of dominant bacteria. After 240 days, the plant height (147.00 ± 0.52 cm), number of tillers (6), and aerial dry weight (144.00 ± 15.99g) of Pennisetum sinese Roxb increased by 5.81%, 200%, and 32.58%, respectively. Analyses of leaves and leaching solution revealed that the highest leaf Mn content (46.84 ± 2.91 μg·g -1 ) being 3.38 times higher than in pure soil, and the leaching solution Mn content (0.66 ± 0.13 μg·g -1 ) was lowest. Our study suggested P. sinese Roxb grown in an improved EMR substrate could be a feasible option for solidification treatment and resource utilization of EMR.

To form blood vessels, endothelial cells rearrange their cytoskeleton, generate traction stresses, migrate, and proliferate, all of which require energy. Despite these energetic costs, stiffening of the extracellular matrix promotes tumor angiogenesis and increases cell contractility. However, the interplay between extracellular matrix, cell contractility, and cellular energetics remains mechanistically unclear. Here, we utilized polyacrylamide substrates with various stiffnesses, a real-time biosensor of ATP, and traction force microscopy to show that endothelial cells exhibit increasing traction forces and energy usage trend as substrate stiffness increases. Inhibition of cytoskeleton reorganization via ROCK inhibition resulted in decreased cellular energy efficiency, and an opposite trend was found when cells were treated with manganese to promote integrin affinity. Altogether, our data reveal a link between matrix stiffness, cell contractility, and cell energetics, suggesting that endothelial cells on stiffer substrates can better convert intracellular energy into cellular traction forces. Given the critical role of cellular metabolism in cell function, our study also suggests that not only energy production but also the efficiency of its use plays a vital role in regulating cell behaviors and may help explain how increased matrix stiffness promotes angiogenesis., Competing Interests: Conflict of interest The authors have no conflicts to disclose., (Copyright © 2024. Published by Elsevier B.V.)

One of the challenges for experimental structural biology in the 21st century is to see chemical reactions happen. Staphylococcus aureus ( S. aureus ) DNA gyrase is a type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology. Drugs, such as gepotidacin, zoliflodacin and the quinolone moxifloxacin, can stabilize these normally transient DNA strand breaks and kill bacteria. Crystal structures of uncleaved DNA with a gepotidacin precursor (2.1 Å GSK2999423) or with doubly cleaved DNA and zoliflodacin (or with its progenitor QPT-1) have been solved in the same P6 1 space-group (a = b ≈ 93 Å, c ≈ 412 Å). This suggests that it may be possible to observe the two DNA cleavage steps (and two DNA-religation steps) in this P6 1 space-group. Here, a 2.58 Å anomalous manganese dataset in this crystal form is solved, and four previous crystal structures (1.98 Å, 2.1 Å, 2.5 Å and 2.65 Å) in this crystal form are re-refined to clarify crystal contacts. The structures clearly suggest a single moving metal mechanism-presented in an accompanying (second) paper. A previously published 2.98 Å structure of a yeast topoisomerase II, which has static disorder around a crystallographic twofold axis, was published as containing two metals at one active site. Re-refined coordinates of this 2.98 Å yeast structure are consistent with other type IIA topoisomerase structures in only having one metal ion at each of the two different active sites.

Manganese is an essential trace element for humans, animals, and plants, but excessive amounts of manganese can cause serious harm to organisms. The biological manganese oxidation process mainly oxidizes Mn(II) through the secretion of unique manganese oxidase by manganese-oxidizing bacteria. The T1 Cu site of multicopper oxidase is the main site for substrate oxidation, and its role is to transfer electrons to TNC, where dioxygen reduction occurs. In this study, methionine (Met) No. 444 interacting with the T1Cu-coordinating amino acid in the multicopper oxidase CopA from Brevibacillus panacihumi MK-8 was mutated to phenylalanine (Phe) and leucine (Leu) by the enzyme. Based on the analysis of enzymatic properties and the structural model, the mutant protein M444F with 4.58 times the catalytic efficiency of the original protein CopA and the mutant protein M444L with 1.67 times the catalytic efficiency of the original protein CopA were obtained. The study showed that the manganese removal rate of the manganese-oxidizing engineered bacterium Rosetta-pET-copA M444L cultured for 7 days was 88.87%, which was 10.77% higher than that of the original engineered bacterium. Overall, this study provides a possibility for the application of genetic engineering in the field of biological manganese removal., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background/objectives: Manganese is an essential nutrient involved in various biological processes, including reproductive health, yet the mechanisms regulating its homeostasis in the testis remain poorly understood., Methods and Results: In this study, we investigated the expression and regulation of key manganese transporters-ZIP8, ZIP14, and ZnT10-in mouse testes. Immunoblotting analyses revealed that ZIP8 is expressed in the testes, while ZIP14 and ZnT10 were undetectable. Using Zip14 knockout ( Zip14 -/- ) mice, which exhibit systemic manganese overload, we discovered a significant increase in manganese levels in the testis, accompanied by an upregulation of ZIP8. Importantly, the levels of other essential metals, such as iron, zinc, and copper, remained unchanged., Conclusions: Our findings suggest that ZIP8 plays a critical role in manganese transport in the testis, and its increased expression may contribute to manganese accumulation in the absence of ZIP14. This study advances our understanding of manganese homeostasis in the testis and its potential impact on male reproductive health.

Solute carrier family 39, member 8 (SLC39A8), is a transmembrane transporter that mediates the cellular uptake of zinc, iron, and manganese (Mn). Human genetic studies document the involvement of SLC39A8 in Mn homeostasis, brain development, and function. However, the role and pathophysiological mechanisms of SLC39A8 in the central nervous system remain elusive. We generated Slc39a8 neuron-specific knockout (Slc39a8-NSKO) mice to study SLC39A8 function in neurons. The Slc39a8-NSKO mice displayed markedly decreased Mn levels in the whole brain and brain regions, especially the cerebellum. Radiotracer studies using 54Mn revealed that Slc39a8-NSKO mice had impaired brain uptake of Mn. Slc39a8-NSKO cerebellums exhibited morphological defects and abnormal dendritic arborization of Purkinje cells. Reduced neurogenesis and increased apoptotic cell death occurred in the cerebellar external granular layer of Slc39a8-NSKO mice. Brain Mn deficiency in Slc39a8-NSKO mice was associated with motor dysfunction. Unbiased RNA-Seq analysis revealed downregulation of key pathways relevant to neurodevelopment and synaptic plasticity, including cAMP signaling pathway genes. We further demonstrated that Slc39a8 was required for the optimal transcriptional response to the cAMP-mediated signaling pathway. In summary, our study highlighted the essential roles of SLC39A8 in brain Mn uptake and cerebellum development and functions.

In this study, we constructed a metal-binding site close to the heme cofactor in myoglobin (Mb) by covalently attaching a nonnative metal-binding ligand of bipyridine to Cys46 through the F46C mutation in the heme distal site. The X-ray structure of the designed enzyme, termed F46C-mBpy Mb, was solved in the Cu(II)-bound form, which revealed the formation of a heterodinuclear center of Cu-His-H 2 O-heme. Cu(II)-F46C-mBpy Mb exhibits not only nitrite reductase reactivity but also cascade reaction activity involving both hydrolysis and oxidation. Furthermore, F46C-mBpy Mb displays Mn-peroxidase activity by the oxidation of Mn 2+ to Mn 3+ using H 2 O 2 as an oxidant. This study shows that the construction of a nonnative metal-binding site close to the heme cofactor is a convenient approach to creating an artificial metalloenzyme with a heterodinuclear center that confers multiple functions.

Manganese ion homeostasis is vital for bacteria and is achieved via manganese-dependent transcription factors. Manganese mediation of transcription factor attachment to the corresponding oligonucleotide sequences can be investigated, e.g. via electrophoretic mobility shift assays (EMSA). Formation of specific biocomplexes leads to differences in the migration pattern upon gel electrophoresis. Focusing on electrophoresis in the gas-phase, applying a nano electrospray gas-phase electrophoretic mobility molecular analyzer (nES GEMMA) also known as nES differential mobility analyzer (nES DMA), and on transcription factors (MntR proteins) from Bacillus subtilis and Mycobacterium tuberculosis, we took interest in the gas-phase electrophoresis of the corresponding biospecific complexes. We compared nES GEMMA, separating analytes in the nanometer regime (a few to several hundred nm in diameter) in the gas-phase in their native state according to particle size, to EMSA data. Indeed we were able to demonstrate manganese-mediated attachment of MntR to target genomic sequences with both analytical techniques. Despite some inherent pitfalls of the nES GEMMA method like analyte/instrument surface interactions, we were able to detect the target complexes. Moreover, we were able to calculate the molecular weight (MW) of the obtained species by application of a correlation function based on nES GEMMA obtained data. As gas-phase electrophoresis also offers the possibility of offline hyphenation to orthogonal analysis techniques, we are confident that nES GEMMA measurements are not just complementary to EMSA, but will offer the possibility of further in-depth characterization of biocomplexes in the future., (© 2024. The Author(s).)

The intricate structure of lignin in straw makes it challenging to hydrolyze, making it a key focus of current research. However, there has been limited study on the effect of enzyme inducer (MnSO 4 ) combined with functional microorganisms on lignin degradation during straw composting. Based on this, four composting treatment groups were set up in this study. Control (CK), functional microorganism addition treatment (F), Mn 2+ enzyme inducer (Mn), and Mn 2+ enzyme inducer coupled with functional microorganism addition treatment (FMn) were tested for composting. Manganese(II)-coupled microorganisms improved lignin degradation: FMn > Mn > F > CK. They increased the lignin loss rate from 25.54 % to 42.61 %. Laccase activity increased from 3.45 to 43.74 U/g and manganese peroxidase activity increased from 145.52 to 264.91 U/g. And gene abundance was increased. Microbial community structure and dominant genera changed. Structural equations support the idea that functional microorganisms coupled with manganese can modify physicochemical indices, thereby regulating gene expression and enhancing enzyme activity. Furthermore, the stimulation of fungal growth and increased extracellular laccase and manganese peroxidase activities can affect the degradation of lignin. This study provides new insights and theoretical support for efficient lignin degradation and efficient resource utilization of compost products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Manganese(IV) (Mn(IV)) reduction coupled to anaerobic ammonium (NH 4 + -N) oxidation (Mnammox) is a recently identified metal oxide-mediated nitrogen (N) loss pathway, holding potential value for the efficient removal of NH 4 + -N from wastewater. However, little is known about the application of Mnammox in wastewater treatment. Here, a novel Mnammox bacterium Aromatoleum evansii (strain MAY27) was screened. Strain MAY27 can utilize MnO 2 as an electron acceptor to achieve NH 4 + -N removal under a low C/N condition (C/N = 0.5). The influencing factors in the Mnammox process and the Mn(IV) reduction driving effect on NH 4 + -N oxidation were investigated. The physiological characteristics of strain MAY27 and differential metabolic pathways were identified through whole-genome sequencing and metabolomic analyses. A significant up-regulation of several key pathways upon the addition of MnO 2 , including glycolysis/gluconeogenesis, transmembrane transporter activity, and oxidoreductase activity. This study contributes to the advancement of biotechnological approaches for treating N-containing wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Autotrophic denitrification technology has gained increasing attention in recent years owing to its effectiveness, economical, and environmentally friendly nature. However, the sluggish reaction rate has emerged as the primary impediment to its widespread application. Herein, a bio-enhanced autotrophic denitrification reactor with modified loofah sponge (LS) immobilized microorganisms was established to achieve efficient denitrification. Under autotrophic conditions, a nitrate removal efficiency of 59.55 % (0.642 mg/L/h) and a manganese removal efficiency of 86.48 % were achieved after bio-enhance, which increased by 20.92 % and 36.34 %. The bioreactor achieved optimal performance with denitrification and manganese removal efficiencies of 99.84 % (1.09 mg/L/h) and 91.88 %. ETSA and 3D-EEM analysis reveled manganese promoting electron transfer and metabolic activity of microorganisms. High-throughput sequencing results revealed as the increase of Mn(II) concentration, Cupriavidus became one of the dominant strains in the reactor. Prediction of metabolic functions results proved the great potential for Mn(II)-autotrophic denitrification of LS bioreactor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Soybean is one of the most important crops for producing high quality oil and protein. Mineral nutrient deficiencies are frequently observed in soybeans. However, there are few studies to understand the absorption process of mineral nutrients in soybeans. Here, we investigated the functions of soybean (Glycine max L.) IRT1.1 (IRON-REGULATED TRANSPORTER 1.1) in the transportation of mineral elements. Heterologous expression of GmIRT1.1 in yeast mutants revealed that GmIRT1.1 compensated for the growth defects of Δfet3fet4 and Δsmf1 mutants under iron (Fe) and manganese (Mn) deficiency conditions, respectively, and enhanced the sensitivity of the Δycf1 mutant to cadmium (Cd) toxicity. Expression analysis revealed that GmIRT1.1 was only significantly induced by Fe deficiency and was primarily expressed in roots. Furthermore, the GmIRT1.1 overexpression lines enhanced Arabidopsis tolerance to Fe deficiency, leading to increased accumulation of Fe in the roots and shoots. Additionally, the transgenic lines increased the sensitivity to Mn and Cd toxicity. Subcellular localization analysis revealed that GmIRT1.1 was localized on the plasma membrane. Moreover, the results obtained from the soybean hairy roots system indicated that the localization of GmIRT1.1 was dependent on the regulation of Fe homeostasis in plant. Consequently, these results suggested that GmIRT1.1 was responsible for the transportation of Fe, Mn and Cd., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Over recent years, we have been living under a pandemic, caused by the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). One of the major virulence factors of Coronaviruses is the Non-structural protein 1 (Nsp1), known to suppress the host cells protein translation machinery, allowing the virus to produce its own proteins, propagate and invade new cells. To unveil the molecular mechanisms of SARS-CoV2 Nsp1, we have addressed its biochemical and biophysical properties in the presence of calcium, magnesium and manganese. Our findings indicate that the protein in solution is a monomer and binds to both manganese and calcium, with high affinity. Surprisingly, our results show that SARS-CoV2 Nsp1 alone displays metal-dependent endonucleolytic activity towards both RNA and DNA, regardless of the presence of host ribosome. These results show Nsp1 as new nuclease within the coronavirus family. Furthermore, the Nsp1 double variant R124A/K125A presents no nuclease activity for RNA, although it retains activity for DNA, suggesting distinct binding sites for DNA and RNA. Thus, we present for the first time, evidence that the activities of Nsp1 are modulated by the presence of different metals, which are proposed to play an important role during viral infection. This research contributes significantly to our understanding of the mechanisms of action of Coronaviruses., (© 2024. The Author(s).)

Manganese (Mn) is considered as an essential element for plant growth. Mn starvation has been shown to affect photosystem II, the site of the Mn 4 CaO 5 cluster responsible for water oxidation. Less is known on the effect of Mn starvation on photosystem I. Here we studied the effects of Mn deficiency in vivo on redox changes of P700 and plastocyanin (Pc) in the liverwort Marchantia polymorpha using the KLAS-NIR spectrophotometer. Far-red illumination is used to excite preferentially photosystem I, thus facilitating cyclic electron transport. Under Mn starvation, we observed slower oxidation of P700 and a decrease in the Pc signal relative to P700. The lower Pc content under Mn deficiency was confirmed by western blots. Re-reduction kinetics of P700 + and Pc + were faster in Mn deficient thalli than in the control. The above findings show that the kinetics studied under Mn deficiency not only depend on the number of available reductants but also on how quickly electrons are transferred from stromal donors via the intersystem chain to Pc + and P700 + . We suggest that under Mn deficiency a structural reorganization of the thylakoid membrane takes place favoring the formation of supercomplexes between ferredoxin, cytochrome b 6 f complex, Pc and photosystem I, and thus an enhanced cyclic electron transport., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anja Krieger-Liszkay reports financial support was provided by French National Research Agency. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Manganese is an important cofactor for numerous biological processes, including defense against reactive oxygen species. A common genetic variant in the manganese transporter SLC39A8 (p.Ala391Thr) has been associated with lower blood levels of manganese and with increases in markers of liver cell damage. Whether the variant confers an increased risk of liver disease is unclear. We tested the association of this variant with biochemical, imaging, and clinical hepatic traits and outcomes in large general population cohorts totaling up to one million individuals, including 991 cases with hepatocellular carcinoma (HCC) and 7191 cases with cirrhosis. We found that the Thr-allele of p.Ala391Thr was associated with slightly higher plasma alanine transaminase and aspartate transaminase, markedly higher corrected T1 on hepatic magnetic resonance imaging, a presumed marker of liver inflammation, and with lower hepatic computed tomography attenuation. However, the variant was not associated with hepatic fat content or with the risk of HCC or cirrhosis. In conclusion, SLC39A8 p.Ala391Thr is associated with biochemical and imaging markers of hepatic inflammation, but the variant does not confer a higher risk of chronic liver disease. We hypothesize that the associations with hepatic imaging traits are due to lower hepatic manganese levels in carriers of the variant. Antioxid. Redox Signal. 41, 591-596. [Figure: see text].

The deterioration of fibre-reinforced sprayed concrete was studied in the Oslofjord subsea tunnel (Norway). At sites with intrusion of saline groundwater resulting in biofilm growth, the concrete exhibited significant concrete deterioration and steel fibre corrosion. Using amplicon sequencing and shotgun metagenomics, the microbial taxa and surveyed potential microbial mechanisms of concrete degradation at two sites over five years were identified. The concrete beneath the biofilm was investigated with polarised light microscopy, scanning electron microscopy and X-ray diffraction. The oxic environment in the tunnel favoured aerobic oxidation processes in nitrogen, sulfur and metal biogeochemical cycling as evidenced by large abundances of metagenome-assembled genomes (MAGs) with potential for oxidation of nitrogen, sulfur, manganese and iron, observed mild acidification of the concrete, and the presence of manganese- and iron oxides. These results suggest that autotrophic microbial populations involved in the cycling of several elements contributed to the corrosion of steel fibres and acidification causing concrete deterioration., (© 2024. The Author(s).)

Manganese (Mn) is an essential trace mineral for brain function, but excessive accumulation can cause irreversible nervous system damage, highlighting the need for proper Mn balance. ZIP14, ZnT10, and ZIP8 are key transporters involved in maintaining Mn homeostasis, particularly in the absorption and excretion of Mn in the intestine and liver. However, their roles in the brain are less understood. The blood-cerebrospinal fluid barrier and the blood-brain barrier, formed by the choroid plexus and brain blood vessels, respectively, are critical for brain protection and brain metal homeostasis. This study identified ZIP14 on the choroid plexus epithelium, and ZIP8 and ZnT10 in brain microvascular tissue. We show that despite significant Mn accumulation in the CSF of Znt10 knockout mice, ZIP14 expression levels in the blood-cerebrospinal fluid barrier remain unchanged, indicating that ZIP14 does not have a compensatory mechanism for regulating Mn uptake in the brain in vivo. Additionally, Mn still enters the CSF without ZIP14 when systemic levels rise. This indicates that alternative transport mechanisms or compensatory pathways ensure Mn balance in the CSF, shedding light on potential strategies for managing Mn-related disorders.

Manganese-oxidizing bacteria (MnOB) produce Mn oxide minerals that can be used by humans for bioremediation, but the purpose for the bacterium is less clear. This study describes the isolation and characterization of cold-tolerant MnOB strains isolated from a compost pile in Morris, Minnesota, USA: Pseudomonas sp. MS-1 and DSV-1. The strains were preliminarily identified as members of species Pseudomonas psychrophila by 16S rRNA analysis and a multi-locus phylogenetic study using a database of 88 genomes from the Pseudomonas genus. However, the average nucleotide identity between these strains and the P. psychrophila sp. CF149 type strain was less than 93%. Thus, the two strains are members of a novel species that diverged from P. psychrophila . DSV-1 and MS-1 are cold tolerant; both grow at 4°C but faster at 24°C. Unlike the mesophilic MnOB P. putida GB-1, both strains are capable of robustly oxidizing Mn at low temperatures. Both DSV-1 and MS-1 genomes contain homologs of several Mn oxidation genes found in P. putida GB-1 ( mnxG , mcoA , mnxS1 , mnxS2, and mnxR ). Random mutagenesis by transposon insertion was successfully performed in both strains and identified genes involved in Mn oxidation that were similar to those found in P. putida GB-1. Our results show that MnOB can be isolated from compost, supporting a role for Mn oxidation in plant waste degradation. The novel isolates Pseudomonas spp. DSV-1 and MS-1 both can oxidize Mn at low temperature and likely employ similar mechanisms and regulation as P. putida GB-1.IMPORTANCEBiogenic Mn oxides have high sorptive capacity and are strong oxidants. These two characteristics make these oxides and the microbes that make them attractive tools for the bioremediation of wastewater and contaminated environments. Identifying MnOB that can be used for bioremediation is an active area of research. As cold-tolerant MnOB, Pseudomonas sp. DSV-1 and MS-1 have the potential to expand the environmental conditions in which biogenic Mn oxide bioremediation can be performed. The similarity of these organisms to the well-characterized MnOB P. putida GB-1 and the ability to manipulate their genomes raise the possibility of modifying them to improve their bioremediation ability., Competing Interests: The authors declare no conflict of interest.

Oxalate decarboxylase is an Mn- and O 2 -dependent enzyme in the bicupin superfamily that catalyzes the redox-neutral disproportionation of the oxalate monoanion to form carbon dioxide and formate. Its best-studied isozyme is from Bacillus subtilis where it is stress-induced under low pH conditions. Current mechanistic schemes assume a monodentate binding mode of the substrate to the N-terminal active site Mn ion to make space for a presumed O 2 molecule, despite the fact that oxalate generally prefers to bind bidentate to Mn. We report on X-band 13 C-electron nuclear double resonance (ENDOR) experiments on 13 C-labeled oxalate bound to the active-site Mn(II) in wild-type oxalate decarboxylase at high pH, the catalytically impaired W96F mutant enzyme at low pH, and Mn(II) in aqueous solution. The ENDOR spectra of these samples are practically identical, which shows that the substrate binds bidentate (κ O , κ O ') to the active site Mn(II) ion. Domain-based local pair natural orbital coupled cluster singles and doubles (DLPNO-CCSD) calculations of the expected 13 C hyperfine coupling constants for bidentate bound oxalate predict ENDOR spectra in good agreement with the experiment, supporting bidentate bound substrate. Geometry optimization of a substrate-bound minimal active site model by density functional theory shows two possible substrate coordination geometries, bidentate and monodentate. The bidentate structure is energetically preferred by ~4.7 kcal/mol. Our results revise a long-standing hypothesis regarding substrate binding in the enzyme and suggest that dioxygen does not bind to the active site Mn ion after substrate binds. The results are in agreement with our recent mechanistic hypothesis of substrate activation via a long-range electron transfer process involving the C-terminal Mn ion.

Plants grow in soils with varying concentrations of microelements, often in the presence of toxic metals e.g. Cd. To cope, they developed molecular mechanisms to regulate metal cross-homeostasis. Understanding underlying complex relationships is key to improving crop productivity. Recent research suggests that the Zn and Cd uptake protein NtZIP5A/B [Zinc-regulated, Iron-regulated transporter-like Proteins (ZIPs)] from tobacco (Nicotiana tabacum L. v. Xanthi) is involved in the regulation of a cross-talk between the two metals. Here, we support this conclusion by showing that RNAi-mediated silencing of NtZIP5A/B resulted in a reduction of Zn accumulation and that this effect was significantly enhanced by the presence of Cd. Our data also point to involvement of NtZIP5B in regulating a cross-talk between Cu, Fe, and Mn. Using yeast growth assays, Cu (but not Fe or Mn) was identified as a substrate for NtZIP5B. Furthermore, GUS-based analysis showed that the tissue-specific activity of the NtZIP5B promoter was different in each of the Zn-/Cu-/Fe-/Mn deficiencies applied with/without Cd. The results indicate that NtZIP5B is involved in maintaining multi-metal homeostasis under conditions of Zn, Cu, Fe, and Mn deficiency, and also in the presence of Cd. It was concluded that the protein regulates the delivery of Zn and Cu specifically to targeted different root cells depending on the Zn/Cu/Fe/Mn status. Importantly, in the presence of Cd, the activity of the NtZIP5B promoter is lost in meristematic cells and increased in mature root cortex cells, which can be considered a manifestation of a defense mechanism against its toxic effects., (© The Author(s) 2024. Published by Oxford University Press.)

Bacteria constitute a significant part of the biomass of the human microbiota, but their interactions are complex and difficult to replicate outside the host. Exploiting the superior resolution of magnetic resonance imaging (MRI) to examine signal parameters of selected human isolates may allow tracking of their dispersion throughout the body. Here we investigate longitudinal and transverse MRI relaxation rates and found significant differences between several bacterial strains. Common commensal strains of lactobacilli display notably high MRI relaxation rates, partially explained by elevated cellular manganese content, while other species contain more iron than manganese. Lactobacillus crispatus show particularly high values, 4-fold greater than any other species; up to 60-fold greater signal than relevant tissue background; and a linear relationship between relaxation rate and fraction of live cells. Different bacterial strains have detectable, repeatable MRI relaxation rates that in the future may enable monitoring of their persistence in the human body for enhanced molecular imaging., (© 2024. The Author(s).)

Manganese (Mn) is indispensable for plant growth, but its excessive uptake in acidic soils leads to toxicity, hampering food safety. Phosphorus (P) application is known to mitigate Mn toxicity, yet the underlying molecular mechanism remains elusive. Here, we conducted physiological and transcriptomic analyses of peach roots response to P supply under Mn toxicity. Manganese treatment disrupted root architecture and caused ultrastructural damage due to oxidative injury. Notably, P application ameliorated the detrimental effects and improved the damaged roots by preventing the shrinkage of cortical cells, epidermis and endodermis, as well as reducing the accumulation of reactive oxygen species (ROS). Transcriptomic analysis revealed the differentially expressed genes enriched in phenylpropanoid biosynthesis, cysteine, methionine and glutathione metabolism under Mn and P treatments. Phosphorus application upregulated the transcripts and activities of core enzymes crucial for lignin biosynthesis, enhancing cell wall integrity. Furthermore, P treatment activated ascorbate-glutathione cycle, augmenting ROS detoxification. Additionally, under Mn toxicity, P application downregulated Mn uptake transporter while enhancing vacuolar sequestration transporter transcripts, reducing Mn uptake and facilitating vacuolar storage. Collectively, P application prevents Mn accumulation in roots by modulating Mn transporters, bolstering lignin biosynthesis and attenuating oxidative stress, thereby improving root growth under Mn toxicity. Our findings provide novel insights into the mechanism of P-mediated alleviation of Mn stress and strategies for managing metal toxicity in peach orchards., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Chronic exposure to elevated levels of manganese (Mn) may cause a neurological disorder referred to as manganism. The transcription factor REST is dysregulated in several neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. REST upregulated tyrosine hydroxylase and induced protection against Mn toxicity in neuronal cultures. In the present study, we investigated if dopaminergic REST plays a critical role in protecting against Mn-induced toxicity in vivo using dopaminergic REST conditional knockout (REST-cKO) mice and REST loxP mice as wild-type (WT) controls. Restoration of REST in the substantia nigra (SN) with neuronal REST AAV vector infusion was performed to further support the role of REST in Mn toxicity. Mice were exposed to Mn (330 μg, intranasal, daily for 3 weeks), followed by behavioral tests and molecular biology experiments. Results showed that Mn decreased REST mRNA/protein levels in the SN-containing midbrain, as well as locomotor activity and motor coordination in WT mice, which were further decreased in REST-cKO mice. Mn-induced mitochondrial insults, such as impairment of fission/fusion and mitophagy, apoptosis, and oxidative stress, in the midbrain of WT mice were more pronounced in REST-cKO mice. However, REST restoration in the SN of REST-cKO mice attenuated Mn-induced neurotoxicity. REST's molecular target for its protection is unclear, but REST attenuated Mn-induced mitochondrial dysregulation, indicating that it is a primary intracellular target for both Mn and REST. These novel findings suggest that dopaminergic REST in the nigrostriatal pathway is critical in protecting against Mn toxicity, underscoring REST as a potential therapeutic target for treating manganism., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The manganese(Mn) redox cycling system in this work was created by combining Mn(IV)-reducing bacteria MFG10 with Mn(II)-oxidizing bacteria HY129. The biomanganese oxides (BMO) generated by strain HY129 were transformed by strain MFG10 to Mn(II), finishing the Mn redox cycling, in which nitrate (NO 3 - -N) was converted to nitrite, which was further reduced to nitrogen gas. The system could achieve 85.7 % and 98.8 % elimination efficiencies of Mn(ⅠⅠ) and NO 3 - -N, respectively, at Mn(ⅠⅠ) = 20.0 mg/L, C/N = 2.0, pH = 6.5, and NO 3 - -N = 16.0 mg/L. The removal of bisphenol A (BPA) and zinc (Zn(II)) at 36 h reached 91.7 % and 89.7 % under the optimal condition, respectively. Furthermore, the Mn redox cycling system can reinforce the metabolic activity and electron transfer activity of microorganisms. The findings showed that the adsorption by bioprecipitation throughout the Mn cycling was responsible for the elimination of Zn(II) and BPA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Major tailings dam failures have occurred recently around the world and resulted in severe environmental impacts, such as metal contamination. Manganese is a metal highly associated with mining activities, largely detected in mining dam collapses. This metal is considered necessary for different organisms, but it can be toxic and cause oxidative stress and genetic damage in fishes. In this study, we investigated the toxic effects of manganese on Astyanax lacustris, by exposing the fish individually to different concentrations of this metal (2.11, 5.00, and 10.43 mg/L) for 96 h. To assess the effects of manganese, we used biochemical biomarkers (glutathione S-transferase, catalase, and acetylcholinesterase enzyme activity) and the manganese bioaccumulation in different tissues (liver and gills). The obtained data showed that only at concentrations of 5.00 mg/L and 10.43 mg/L the activity of glutathione S-transferase differed significantly. Additionally, the acetylcholinesterase activity in the brain tissue was inhibited. The highest level of manganese bioaccumulation was observed in the liver and branchial tissue. Overall, we concluded that high concentrations of manganese may cause physiological changes in Astyanax lacustris., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The effect mechanism of Mn on Cd uptake by Celosia argentea was investigated via a series of hydroponics experiments. The results showed that different manganese treatments had different effects on Cd uptake by C. argentea. Mn pretreatment increased Cd uptake by root protoplasts at Cd concentrations (4 and 6 μM). Protoplasts reached peak Cd uptake rate at 6 μM Cd and 25 °C, with 67.71 ± 0.13 μM h -1 mL -1 in the control, and 77.99 ± 0.49 μM h -1 mL -1 in the 50 μM Mn pretreatment group. However, simultaneous treatment with Cd and Mn reduced the Cd 2+ uptake by root protoplasts. This discrepancy may be attributed to the fact that cadmium and manganese share some transporters in root cells. The transcriptome analysis in roots revealed that ten genes (including ABCC, ABCA, ABCG, ABCB, ABC1, BZIP19, and ZIP5) were significantly upregulated in response to Mn stress (p < 0.05). These genes regulate the expression of transporters belonging to the ABC, and ZIP families, which may be involved in Cd uptake by root cells of C. argentea. Mn pretreatment upregulates the expression of Mn/Cd transporters, enhancing Cd uptake by root protoplasts. For the simultaneous treatment of Cd and Mn, inhibition of Cd uptake was due to the competition of the same transporters. These findings provide helpful insights for understanding the mechanism of Mn and Cd uptake in hyperaccumulators and give implications to improve the phytoremediation of Cd-contaminated soil by C. argentea., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Improper electronic waste management in the world especially in developing countries such as Iran has resulted in environmental pollution. Copper, nickel, and manganese are from the most concerned soil contaminating heavy metals which found in many electronic devices that are not properly processed. The aim of this study was to investigate the biological removal of copper, nickel, and manganese by Bacillus species isolated from a landfill of electronic waste (Zainal Pass hills located in Isfahan, Iran) which is the and to produce nanoparticles from the studied metals by the isolated bacteria. The amounts of copper, nickel, and manganese in the soil was measured as 1.9 × 10 4 mg/kg, 0.011 × 10 4 mg/kg and 0.013 × 10 4 mg/kg, respectively based on ICP-OES analysis, which was significantly higher than normal (0.02 mg/kg, 0.05 mg/kg, and 2 mg/kg, respectively. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of metals on the bacterial isolates was determined. The biosorption of metals by the bacteria was evaluated by inductively coupled plasma optical emission spectroscopy (ICP-OES). The metal nanoparticles were synthetized utilizing the isolates in culture media containing the heavy metals with the concentrations to which the isolates had shown resistance. X ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS) were used for the evaluation of the fabrication of the produced metal nanoparticles. Based on the findings of this study, a total of 15 bacterial isolates were obtained from the soil samples. The obtained MICs of copper, nickel, and manganese on the isolates were 40-300 mM, 4-10 mM, and 60-120 mM, respectively. The most resistant isolates to copper were FM1 and FM2 which were able to bio-remove 79.81% and 68.69% of the metal, respectively. FM4 and FM5 were respectively the most resistant isolate to nickel and manganese and were able to bio-remove 86.74% and 91.96% of the metals, respectively. FM1, FM2, FM4, and FM5 was molecularly identified as Bacillus cereus, Bacillus thuringiensis, Bacillus paramycoides, and Bacillus wiedmannii, respectively. The results of XRD, SEM and EDS showed conversion of the copper and manganese into spherical and oval nanoparticles with the approximate sizes of 20-40 nm. Due to the fact that the novel strains in this study showed high resistance to copper, nickel, and manganese and high adsorption of the metals, they can be used in the future, as suitable strains for the bio-removal of these metals from electronic and other industrial wastes., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Microbial manganese (Mn) oxidation, predominantly occurs within the anaerobic-aerobic interfaces, plays an important role in environmental pollution remediation. The anaerobic-aerobic transition zones, notably riparian and lakeside zones, are hotspots for algae-bacteria interactions. Here, we adopted a Mn(II)-oxidizing bacterium Pseudomonas sp. QJX-1 to investigate the impact of algae on microbial Mn(II) oxidation and verify the underlying mechanisms. Interestingly, we achieved a remarkable enhancement in bacterial Mn(II)-oxidizing activity within the algae-bacteria co-culture, despite the inability to oxidize Mn(II) for the algae used in this study. In addition, the bacterial density almost remains constant in the presence of algal cells. Therefore, the increased Mn(II) oxidation by QJX-1 in the presence of algae cannot be due to the increased biomass. Within this co-culture system, the Mn(II) oxidation rate surged to an impressive 0.23 mg/L/h, in stark contrast to 0.02 mg/L/h recorded within pure QJX-1 system. The presence of algae could inhibit the Fe-S cluster activity of QJX-1 by the produced active substance in co-culture, and result in the acceleration of extracellular superoxide production due to the impairment of electron transfer functions located in QJX-1 cell membranes. Moreover, elevated peroxidase gene expression and heightened extracellular catalase activity not only expedited Mn(II) ions oxidation but also facilitated conversion of intermediate Mn(III) ions into microbial Mn oxides, achieved through the degradation of hydrogen peroxide. Therefore, the acceleration of extracellular superoxide production and the decomposition of hydrogen peroxide are identified as the principal mechanisms behind the observed enhancement in Mn(II) oxidation within algae-bacteria co-cultures. Our findings highlight the need to consider the effect of algae on microbial Mn(II) oxidation, which plays an important role in the environmental pollution remediation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Inhalation of welding fumes can cause metal accumulation in the brain, leading to Parkinsonian-like symptoms. Metal accumulation and altered neurochemical profiles have been observed using magnetic resonance imaging (MRI) in highly exposed welders, being associated with decreased motor function and cognition. While MRI is impractical to use as a health risk assessment tool in occupational settings, toenail metal levels are easier to assess and have been demonstrated to reflect an exposure window of 7-12 months in the past. Yet, it is unclear whether toenail metal levels are associated with brain metal levels or changes in metabolism, which are the root of potential health concerns. This study investigates whether toenail manganese (Mn) and iron (Fe) levels, assessed at several time points, correlate with brain Mn and Fe levels, measured by MRI, as well as brain GABA, glutamate (Glu), and glutathione (GSH) levels, measured by Magnetic Resonance Spectroscopy (MRS), in seventeen Mn-exposed welders. Quantitative T1 and R2* MRI maps of the whole brain, along with GABA, Glu, and GSH MRS measurements from the thalamus and cerebellum were acquired at baseline (T0). Toenail clippings were collected at T0 and every three months after the MRI for a year to account for different exposure periods being reflected by toenail clippings and MRI. Spearman correlations of toenail metal levels were run against brain metal and metabolite levels, but no significant associations were found for Mn at any timepoint. Cerebellar GSH positively correlated with toenail Fe clipped twelve months after the MRI (p = 0.05), suggesting an association with Fe exposure at the time of the MRI. Neither thalamic GABA nor Glu correlated with toenail Fe levels. In conclusion, this study cannot support toenail Mn as a proxy for brain Mn levels or metabolic changes, while toenail Fe appears linked to brain metabolic alterations, underscoring the importance of considering other metals, including Fe, in studying Mn neurotoxicity., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ulrike Dydak reports a relationship with American Regent Inc that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Crop manganese (Mn) accumulation and the associated human health risks stemming from excessive intake of high Mn crop foods have attracted attention. However, there is limited information available concerning the impact of plastic film mulching (PFM) on Mn concentration in cereal grains and the health risks associated with Mn intake by the human body. Field experiments were conducted from 2014 to 2016 at seven sites in the drylands of a typical wheat-growing region in China to assess the effect of PFM on grain Mn concentration, Mn accumulation and distribution in winter wheat plants, and the potential risk of Mn intake and optimal grain intake for human health. The multi-site study results revealed that grain Mn concentration and bioavailability were significantly higher under PFM compared to no mulching. Similarly, PFM was found to enhance aboveground Mn accumulation at the anthesis stage by 17.5 %, Mn harvest index by 3.9 %, grain Mn accumulation by 28.9 %, and available Mn concentration in the soil by 10.9 %. The increased uptake and accumulation of Mn in wheat plants, leading to elevated grain Mn concentration, were primarily attributed to the improved availability of Mn and moisture in the soil under PFM treatment. Furthermore, a health risk assessment indicated that long-term consumption of whole wheat grains from PFM treatment could potentially pose a non-carcinogenic risk of Mn for children and adolescents residing in rural areas. Therefore, this study established upper limits for daily consumption of whole wheat grains based on the specific needs of local residents. The findings of this research underscore the potential health risks associated with consuming grain crops grown in PFM crop production systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study explores the metal oxide-mediated NH 4 + -N reduction process: manganese ammonia oxidation efficiency, influencing factors and its resistance to low-temperature environments in water bodies. After 177d of stabilized startup of an up-flow reactor, NH 4 + -N removal efficiency was 63.51 %, total nitrogen (TN) removal rate was 0.021 kg/(m 3 .d), and effluent Mn 2+ concentration was 1.503 mg/L, which was in dynamic equilibrium. X-ray photoelectron spectroscopy exhibited manganese valence state 3.29, similar to biological manganese oxidation. High-throughput sequencing revealed that phyla's denitrification function increased relative abundance, and manganese-reducing bacterial genera appeared. The batch test showed that 5 mg MnO 2 had NH 4 + -N removal at 85.01 %. After 44 days, NH 4 + -N removal efficiency was 77.47 %, effluent Mn 2+ concentration was 3.280 mg/L, TN removal rate was 0.063 kg/(m 3 .d). The long-term effect of the influent load change on the denitrification and Mnammox efficiency at 25 ∼ 15 °C was examined. Effluent Mn 2+ concentration was 1.811 mg/L was relatively stable. Manganese valence decreased from 3.29 to 3.20, Mn 4+ decreased by 9.58 %, while Mn 3+ and Mn 2+ increased by 10.94 % and 1.37 %, respectively. A new phylum Thermotogota and genus SBR1031 appeared in the microbial community., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: An issue of pressing concern is the manganese contamination in farmland soils adjacent to industrial areas. To address this, intercropping hyperaccumulator plants with crops emerges as a sustainable approach to ensuring food security. This study aims to investigate the influence of intercropping Sedum alfredii with maize or soybean on their growth and the dynamics of manganese accumulation through field experiments., Results: The results showed that compared with monoculture, the Sedum alfredii-maize intercropping system exhibited a land equivalent ratio (LER) of 1.89, signifying a 71.13% augmentation in bioaccumulation amount (BCA). Additionally, it led to a significant reduction in manganese content in various organs, ranging from 17.05% to 25.50%. However, the Sedum alfredii-soybean intercropping system demonstrated a LER of 1.94, accompanied by a 66.11% increase in BCA, but did not significantly reduce the manganese content in the roots, stems, and pods of soybeans. Furthermore, manganese accumulation in maize and soybean grains was primarily attributed to the aboveground translocation of manganese. The intercropping effect on blocking manganese absorption of maize during growth and maturity is primarily attributed to the earlier manganese accumulation in intercropped maize by 2.63 to 4.35 days, and a reduction of 21.95% in the maximum manganese accumulation rate., Conclusions: The study found that manganese accumulation dynamics vary significantly depending on the crop family. Intercropping Sedum alfredii with maize enhances land-use efficiency and reduces manganese uptake by crops, making it a promising strategy for remediating manganese-contaminated farmland near industrial areas. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Zrt/Irt-like protein 8 (ZIP8), which is a Zn transporter, plays a pivotal role as a Mn transporter. Recent studies have shown that a ZIP8 SNP (rs13107325 C→T, A391T) is associated with multiple diseases, likely by causing systemic Mn deficiency. However, the underlying molecular mechanisms remain unclear. We attempted to address this issue in cell-based experiments using Madin-Darby canine kidney cells stably expressing ZIP8 WT or the A391T SNP mutant under the control of the Tet-regulatable promoter. We showed that the A391T mutant lost the property of Mn-responsive accumulation on the cell surface, which was observed in WT ZIP8. We also showed that the loss of Mn-responsive accumulation of A391T mutant was associated with its reduced Mn uptake, compared with WT ZIP8, in the Mn uptake assay using the radioisotope 54Mn. Our results potentially explain how the ZIP8 A391T substitution is associated with disease pathogenesis caused by Mn deficiency., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

The global manganese cycle relies on microbes to oxidize soluble Mn(II) to insoluble Mn(IV) oxides. Some microbes require peroxide or superoxide as oxidants, but others can use O 2 directly, via multicopper oxidase (MCO) enzymes. One of these, MnxG from Bacillus sp. strain PL-12, was isolated in tight association with small accessory proteins, MnxE and MnxF. The protein complex, called Mnx, has eluded crystallization efforts, but we now report the 3D structure of a point mutant using cryo-EM single particle analysis, cross-linking mass spectrometry, and AlphaFold Multimer prediction. The β-sheet-rich complex features MnxG enzyme, capped by a heterohexameric ring of alternating MnxE and MnxF subunits, and a tunnel that runs through MnxG and its MnxE 3 F 3 cap. The tunnel dimensions and charges can accommodate the mechanistically inferred binuclear manganese intermediates. Comparison with the Fe(II)-oxidizing MCO, ceruloplasmin, identifies likely coordinating groups for the Mn(II) substrate, at the entrance to the tunnel. Thus, the 3D structure provides a rationale for the established manganese oxidase mechanism, and a platform for further experiments to elucidate mechanistic details of manganese biomineralization.

Competing Interests: Competing interests statement:The authors declare no competing interest.

The electrolytic manganese industry produces a large amount of electrolytic manganese residue (EMR). Soluble Mn, NH 4 + -N, and other pollutants may be released from the open-air stacked EMR and transported to the environment along with rainfall or surface runoff. Aqueous EMR solution (AES) generally contains various elements required for plant growth, and phytoremediation can be applied to remove these pollutants from AES. Since the contents of Fe and Co vary greatly in AES depending on the ore sources as well as the pre-treatment processes, the presence of bioavailable Fe and Co at different levels may affect plant growth, the rhizosphere microbes, and pollutant removal. The present study investigated the in-situ removal of Mn(II) and NH 4 + -N from AES solution using free floating aquatic plant Pistia stratiotes, focusing especially on the effects of Fe/Co presence and rhizospheric microbe synergistic involvement on contaminant removal. The results showed that 69.08% of Mn and 94.99% of NH 4 + -N were removed by P. stratiotes in 24 d. Both the presence of Fe(II) and Co(II) facilitated the Mn(II) immobilization and increased Mn(II) removal by 19-31% due to the enhanced peroxidase activity and the increased Mn accumulating in roots The complete removal of Mn from AES was found in the presence of Fe(II) at 2 mg L -1 or Co(II) at 0.5 mg L -1 and more than 51% accumulated Mn in the roots was stored in the vacuole and cytoplasm. BioMnO x was found on the surface of the roots, revealing that rhizofiltration, rhizospheric plaque/biofilm formation, and Mn biogeochemical cycle exert synergic effects on Mn(II) immobilization. The findings of the present study demonstrate the feasibility of using P. stratiotes in the treatment of aqueous EMR solutions and the presence of an appropriate amount of bio-available Fe and Co can promote the removal of Mn(II) and NH 4 + -N., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The development of the mining industry and the overuse of inorganic fertilizers have led to an excess of manganese (Mn) in the soil, thereby, contaminating the soil environment and people's health. On heavy metal-contaminated soils, the combined arbuscular mycorrhizal fungi (AMF)-phytoremediation technique becomes a hotspot because of its environmentally friendly, in situ remediation. AMF inoculation often leads to a decrease in host Mn acquisition, which provides a basis for its application in phytoremediation of contaminated soils. Moreover, the utilization value of native AMF is greater than that of exotic AMF, because native AMF can adapt better to Mn-contaminated soils. In addition to the fact that AMF enhance plant Mn tolerance responses such as regionalization, organic matter chelation, limiting uptake and efflux, and so on, AMF also develop plant-independent fungal pathways such as direct biosorption of Mn by mycorrhizal hyphae, fungal Mn transporter genes, and sequestration of Mn by mycorrhizal hyphae, glomalin, and arbuscule-containing root cortical cells, which together mitigate excessive Mn toxicity to plants. Clarifying AMF-plant interactions under Mn stress will provide support for utilizing AMF as a phytoremediation in Mn-contaminated soils. The review reveals in detail how AMF develop its own mechanisms for responding to excess Mn and how AMF enhance plant Mn tolerance, accompanied by perspectives for future research., Competing Interests: Declaration of competing interest Authors declare there is no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

1. Tibial dyschondroplasia (TD) is a skeletal disorder in broilers that has financial implications, necessitating dietary modifications to reduce the prevalence of this disease. This study explored how arginine silicate inositol complex (ASI) supplementation affected tibial growth plate (TGP) and overall bone health in broilers with manganese (Mn) deficiency-induced TD.2. A total of 240 broiler chicks were divided into four groups, each consisting of 60 birds (15 replicates of four broilers each) as follows: i) Control, with 60 mg Mn per kg of diet; ii) ASI, with 60 mg Mn and 1 g ASI per kg of diet; iii) TD, with 22 mg Mn per kg of diet, and iv) TD+ASI, with 22 mg Mn and 1 g ASI per kg of diet.3. It was found that ASI supplementation increased tibial bone length in Mn-deficient TD broilers ( p = 0.007). There was no Mn x ASI interaction for other bone morphometry variables ( p  > 0.05). However, both tibial bone mineral content and density were affected by Mn and ASI ( p  < 0.05). With ASI supplementation, serum bone-specific alkaline phosphatase and osteocalcin levels were elevated in the TD+ASI group compared to the TD group ( p  < 0.001). In the TD group, osteoprotegerin (OPG) levels in the TGP decreased compared to the control groups ( p  < 0.001).4. In contrast, ASI supplementation in the TD broilers counteracted the decrease in OPG compared to TD broilers without ASI supplementation ( p  < 0.001). The Mn level and ASI supplementation significantly influenced the OPG/receptor activator of the nuclear factor-κB ligand ratio ( p  < 0.001).5. In conclusion, the results demonstrated that inclusion of ASI in broiler diets could enhance bone formation variables by controlling OPG levels in the TGP, potentially serving as an effective method to decrease the occurrence of TD.

Current nanozyme applications rely heavily on peroxidase-like nanozymes and are limited to a specific temperature range, despite notable advancements in nanozyme development. In this work, we designed novel Mn-based metal organic frameworks (UoZ-4), with excellent oxidase mimic activity towards common substrates. UoZ-4 showed excellent oxidase-like activity (with Km 0.072 mM) in a wide range of temperature, from 10 °C to 100 °C with almost no activity loss, making it a very strong candidate for psychrophilic and thermophilic applications. Ascorbic acid, cysteine, and glutathione could quench the appearance of the blue color of oxTMB, led us to design a visual-based sensing platform for detection of total antioxidant capacity (TAC) in cold, mild and hot conditions. The visual mode successfully assessed TAC in citrus fruits with satisfactory recovery and precisions. Cold/hot adapted and magnetic property will broaden the horizon of nanozyme applications and breaks the notion of the temperature limitation of enzymes., Competing Interests: Declaration of competing interest The authors declare there no competing financial interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)