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The recovery of rare earth elements (REEs) is a major issue based on environmental governance and sustainable resource utilization. In this study, we developed a novel hydrogel material (Fe/Mn@ALG) by anchoring Fe/Mn NPs on alginate spheres, where Fe/Mn NPs were in-situ synthesized using Euphorbia cochinchensi leaf extract as reduced and protection agents. The Fe/Mn@ALG was applied directly to real mine wastewater, generating efficient and selective recovery of REEs with the coexistence of numerous competing metal ions. As results have shown, Fe/Mn@ALG was a useful adsorbent for REEs with an adsorption efficiency 78.62 % achieved, which was also confirmed by distribution coefficients (K d ), up to 2451.66 mL·g -1 . Furthermore, Fe/Mn@ALG exhibited preferential response to REEs over other metal ions with the separation factor (SF) being up to 240. This great adsorption performance and selectivity toward REEs were attributed to its specific surface area, oxygen-rich functional groups and negatively charged surface in acid wastewater. Furthermore, REEs could be greatly desorbed from Fe/Mn@ALG with output concentration being three times higher than the initial concentration. Additionally, Fe/Mn@ALG maintained its good adsorption performance with efficiency reaching 72.24 % after five reuses. Overall, Fe/Mn@ALG can be considered as a promising candidate for wastewater remediation and sustainable management of resources., 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.)

Widespread contamination of soils by neurotoxic lead ions (Pb) posed a serious risk to food security, but efficient treatment in soil remained a challenge. For the adsorption of Pb, DFT calculations were firstly performed to predict the synergistic effect of sulfhydryl-hydroxyl groups as well as the ability of sulfur ions to strengthen Pb-OH bonding. Consequently, Mn-S functionalized coffee ground biochar (MSBC) was then synthesized utilizing precipitation and impregnation methods. In the soil experiment, the removal efficiency of Pb reached 82.92%, exceeding the previous research results. In addition, it successfully restored the polluted farmland near the mining area and increased the plant height of Swiss chard by 186.23%. Subsequently, synergistic effect of sulfhydryl-hydroxyl groups was confirmed by XPS, FT-IR, and DFT calculations. Furthermore, the factors affecting the structural stability of O-Pb-S were discussed by regression analysis. These reflected that MSBC can enhance the removal efficiency of Pb in soil by mitigating the competition of impurity ions to adsorption sites. These findings may provide new insights into the development of the specific passivation materials for other heavy metals., 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.)

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.)

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.)

Enzyme catalytic cascade reactions based on peroxidase nanozymes and natural enzymes have aroused extensive attention in analytical fields. However, a majority of peroxidase nanozymes perform well only in acidic environments, resulting in their optimal pH mismatch with a neutral pH of natural enzymes, further restricting their application in biochemical sensing. Herein, Mn-doped CeO 2 (Mn/CeO 2 ) performing enhanced peroxidase-like activity at neutral conditions was prepared via a facile and feasible strategy. An effective enzyme cascade catalysis system via integrating glucose oxidase (GOx) with Mn/CeO 2 was developed for one-pot detection of glucose in serum at neutral conditions. Using one-pot multistep catalytic reactions, this work provided a detection platform that allows for faster detection and easier operations than traditional methods. Under optimized conditions, our assay performed a sensitive detection of glucose ranging from 2.0 μΜ to 300 μΜ and a low detection limit of 0.279 μΜ. Notably, favorable analytical outcomes for glucose detection in serum samples were obtained, exhibiting potential applications in clinical diagnosis., 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 work investigated the range of substitution of two biologically relevant ions, namely Mn 2+ and Co 2+ , into the structure of β-tricalcium phosphate, as well as their influence on bone cells response. To this aim, β-TCP was synthesized by solid state reaction in the presence of increasing amount of the substituent ions. The results of the X-ray diffraction analysis reveal that just limited amounts of these ions can enter into the β-TCP structure: 15 at% and 20 at% for cobalt and manganese, respectively. Substitution provokes aggregation of the micrometric particles and reduction of the lattice constants. In particular, the dimension of the c-parameter exhibits a discontinuity at about 10 at% for both cations, although with different trend. Moreover, Rietveld refinement demonstrates a clear preference of both manganese and cobalt for the octahedral site (V). The influence of these ions on cell response was tested on osteoblast, osteoclast and endothelial cells. The results indicate that the presence of manganese promotes a good osteoblast viability, significantly enhances the expression of osteoblast key genes and the angiogenic process of endothelial cells, while inhibiting osteoclast resorption. At variance, osteoblast viability appears reduced in the presence of Co samples, on which osteoblast genes reach higher expression than on β-TCP just in a few cases. On the other hand, the results clearly show that cobalt significantly stimulates the angiogenic process and inhibits osteoclast resorption., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Atom-dispersed low-coordinated transition metal-N x catalysts exhibit excellent efficiency in activating peroxydisulfate (PDS) for environmental remediation. However, their catalytic performance is limited due to metal-N coordination number and single-atom loading amount. In this study, low-coordinated nitrogen-doped graphene oxide (GO) confined single-atom Mn catalyst (Mn-SA/NGO) was synthesized by molten salt-assisted pyrolysis and coupled to PDS for degradation of tetracycline (TC) in water. Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (AC-HAADF-STEM) and X-ray absorption fine structure spectroscopy (XAFS) analysis showed the successful doping of single-atom Mn (weight percentage 1.6%) onto GO and the formation of low-coordinated Mn-N 2 sites. The optimized parameters obtained by Box-Behnken Design achieved 100% TC removal in both prediction and experimental results. The Mn-SA/NGO + PDS system had strong anti-interference ability for TC removal in the presence of anions. Besides, Mn-SA/NGO possessed good reusability and stability. O 2 •- , •OH, and 1 O 2 were the main active species for TC degradation, and the TC mineralization reached 85.1%. Density functional theory (DFT) calculations confirmed that the introduction of single atoms Mn could effectively enhance adsorption and activation of PDS. The findings provide a reference for the synthesis of high-performance single-atom catalysts for effective removal of antibiotics., 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 Inc. All rights reserved.)

There is great interest in fabricating devices that can detect and remove water pollutants, especially heavy metal ions and dyes from wastewater, to promote sustainable water use. In this study, an extract of Borassus flabellifer leaves (BoF-LE) was used to synthesize silver nanoparticles (BoF-AgNPs), with the BoF-LE serving as a reducing and capping agent. The sensitivity and selectivity of BoF-AgNPs for Mn(II) ions were tested by comparing with the control sample and other competent metal ions. Our results showed that BoF-AgNPs are extremely sensitive and selective in detecting Mn(II) ions, with a detection limit of 0.3 ppb. HR-TEM, UV-Vis spectroscopy, and DLS investigations were used to confirm that BoF-AgNPs detect Mn(II) ions by an aggregation-based mechanism. Additionally, it was found that BoF-AgNPs are effective in rapidly decolorizing MB dye, as demonstrated by their ability to decolorize MB by 92.66% within 7 min. This study is the first to report successful synthesis of BoF-AgNPs and their two applications, which are enabled with an Inhibit-AND logic gate. Using BoF-AgNPs to detect and degrade water pollutants may promote sustainable water use., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Kritika S. Sharma reports financial support was provided by Department of Science and Technology (DST), Ministry of Science & Technology, India. 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.)

Removal of Mn(II) is an essential step for addressing water discoloration in water treatment utilities worldwide. However, conventional chlorination suffers from poor oxidation of Mn(II) due to its low homogeneous oxidation kinetics. This study explored the oxidation capability of a new chemical dosing strategy employing peroxymonosulfate (PMS) to assist the chlorination process (PMS@Cl 2 ) for effective Mn(II) oxidation. The study comprehensively explored both oxidation kinetics and underlying mechanisms associated with homogeneous and heterogeneous oxidation within the PMS@Cl 2 system. At an [Mn(II)] 0 of 1 mg/L, chlorination demonstrated inability in oxidizing Mn(II), with <10 % oxidation even at an elevated [Cl 2 ] of 150 μM (∼10 mg/L). By contrast, PMS completely oxidized 100 % Mn(II) within a 30-minute reaction at a much lower [PMS] of 60 μM (k obs = 0.07 min -1 and t 1/2 = 9 min), demonstrating its superior Mn(II) oxidation kinetics (over one order of magnitude faster than conventional chlorine). PMS@Cl 2 exhibited an interesting synergistic benefit when combining a lower dose PMS with a higher routine dose Cl 2 (loPMS@hiCl 2 ), e.g. [PMS]:[Cl 2 ] at 15:30 or 30:30 μM. Both conditions achieved 100 % Mn(II) oxidation, with even better values of k obs and t 1/2 (0.16-0.17 min -1 and ∼4 min) relative to PMS alone at 60 µM. The synergic benefit of PMS@Cl 2 was attributed to distinct functions played by PMS and Cl 2 in both homogeneous and heterogeneous oxidation processes. Reactive species identification excluded the possible involvement of SO 4 •- , OH • , or chlorine radicals in the homogeneous oxidation of the PMS@Cl 2 system. Instead, the dominant species was O 2 •- radical generated during the reaction of Mn(II) and PMS. Furthermore, the heterogeneous oxidation emphasized the important role of combining Cl 2 dosing, which demonstrated an increased reactivity and electron transfer with the Mn-O-Mn complex, surpassing PMS. Overall, heterogeneous oxidation accelerated the oxidation kinetics of the PMS@Cl 2 system by 1.1-2 orders of magnitude relative to the homogeneous oxidation of Cl 2 alone. We here demonstrated that PMS@Cl 2 could offer a more efficient mean of soluble Mn(II) mitigation, achieved with a relatively low routine dose of oxidant in a short reaction period. The outcomes of this study would address the existing limitations of traditional chlorine oxidation, minimizing the trade-offs associated with high residual chlorine levels after treatments for soluble manganese-containing water., 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.)

A pilot-scale filtration system was adopted to prepare filter media with catalytic activity to remove manganese (Mn 2+ ) and ammonium (NH 4 + -N). Three different combinations of oxidants (KMnO 4 and K 2 FeO 4 ) and reductants (MnSO 4 and FeCl 2 ) were used during the start-up period. Filter R3 started up by KMnO 4 and FeCl 2 (Mn 7+ →MnO x ) exhibited excellent catalytic property, and the NH 4 + -N and Mn 2+ removal efficiency reached over 80% on the 10 th and 35 th days, respectively. Filter R1 started up by K 2 FeO 4 and MnSO 4 (MnO x ←Mn 2+ ) exhibited the worst catalytic property. Filter R2 started up by KMnO 4 and MnSO 4 (Mn 7+ →MnO x ←Mn 2+ ) were in between. According to Zeta potential results, the Mn-based oxides (MnO x ) formed by Mn 7+ →MnO x performed the highest pH IEP and pH PZC . The higher the pH IEP and pH PZC , the more unfavorable the cation adsorption. However, it was inconsistent with its excellent Mn 2+ and NH 4 + -N removal abilities, implying that catalytic oxidation played a key role. Combined with XRD and XPS analysis, the results showed that the MnO x produced by the reduction of KMnO 4 showed early formation of buserite crystals, high degree of amorphous, high content of Mn 3+ and lattice oxygen with the higher activity to form defects. The above results showed that MnO x produced by the reduction of KMnO 4 was more conducive to the formation of active species for catalytic oxidation of NH 4 + -N and Mn 2+ removal. This study provides new insights on the formation mechanisms of the active MnO x that could catalytic oxidation of NH 4 + -N and Mn 2+ ., 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 © 2023. Published by Elsevier B.V.)

With excessive Mn(Ⅱ) and Cu(Ⅱ) pollution in aquatic environments posing potential health risks to inhabitants, the emergence of carbon capture, utilization and storage (CCUS) technology has promoted the improvement of heavy metal remediation technologies. Using hydrothermal sediment as a crystal seed, rhamnolipid was used to mediate biomimetic mineralization to prepare hydrated magnesium carbonate (HMC) composites to enhance the Mn(Ⅱ)/Cu(Ⅱ) adsorption performance of alginate hydrogels. Hydrothermal sediment is beneficial for accelerating biomimetic mineralization, while rhamnolipid can induce a crystalline phase transformation from dypingite to nesquehonite. The addition of sediment significantly enhanced the compressive mechanical properties and thermal stability of the hydrogels. The adsorption performances of the nesquehonite and dypingite hydrogels were better for Mn(II) and Cu(II), respectively. An increase in the amount of sediment improved the adsorption of Cu(II) by the hydrogels appropriately, resulting in stronger selectivity for Cu(II). The adsorption of Mn(II) and Cu(II) on the hydrogel beads was thermodynamically spontaneous. The inhibitory effects of sodium dodecyl benzene sulfonate (SDBS), fulvic acid (FA) and alginate on Cu(II) adsorption were more obvious than those of bovine serum albumin (BSA). Both the complexation of functional groups on alginate and mineralization by HMC participated in the adsorption of Mn(II) and Cu(II)., 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.)

Ultrafiltration (UF) is a highly efficient technique for algal-rich water purification, but it is heavily contaminated due to the complex water characteristics. To solve this problem, potassium permanganate (KMnO 4 ) oxidation enhanced with sodium sulfite (Na 2 SO 3 ) was proposed as a pretreatment means. The results showed that the end-normalized flux was elevated from 0.10 to 0.91, and the reversible fouling resistance was reduced by 99.95%. The membrane fouling mechanism also changed obviously, without the generation of cake filtration. Regarding the properties of algal-rich water, the zeta potential was decreased from -29.50 to -5.87 mV after KMnO 4 /Na 2 SO 3 pretreatment, suggesting that the electrostatic repulsion was significantly reduced. Meanwhile, the fluorescent components in algal-rich water were significantly eliminated, and the removal of dissolved organic carbon was increased to 67.46%. In the KMnO 4 /Na 2 SO 3 process, reactive manganese species (i.e., Mn(V), Mn(III) and MnO 2 ) and reactive oxygen species (i.e., SO 4 •- and • OH) played major roles in purifying algal-rich water. Specifically, SO 4 •- , • OH, Mn(V) and Mn(III) could effectively oxidize algal pollutants. Simultaneously, the in-situ adsorption and coagulation of MnO 2 could accelerate the formation of flocs by decreasing the electrostatic repulsion between cells, and protect the algal cells from being excessive oxidized. Overall, the KMnO 4 /Na 2 SO 3 process showed significant potential for membrane fouling alleviation in purifying algal-rich water., 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 Inc. All rights reserved.)

Dissolved Mn(III), as a potent one-electron transfer oxidant, is ubiquitous in natural waters and sediments and actively involved in the transformation of organics in biogeochemical processes and water treatment. However, the important role of Mn(III) has long been overlooked because of its short life. This study was the first to investigate the performance of Mn(III) in organoarsenic transformation and to highlight the environmental implications. Both homogeneous and heterogeneous Mn(III)-based systems were effective to remove p-arsanilic acid (p-ASA, 15 μM) with degradation efficiency approaching 40.4 %-98.3 %. Two degradation pathways of p-ASA were proposed, in which As-C bond and amino group were vulnerable sites to Mn(III) attack, leading to the formation of more toxic arsenate (As(V)) and nitarsone. Through transforming organoarsenic to inorganic arsenic species, the removal efficiency of total arsenic and dissolved organics were enhanced to 65.1 %-95.5 % and 16.6 %-36.6 %, respectively, by post-treatment of coagulation or adsorption, accompanied with significant reduction of cytotoxicity and environmental risks. Particularly, polymeric ferric sulfate and granular activated alumina showed superior performance in the total As removal. Moreover, oxidation efficiency of Mn(III) was hardly affected by common cations and anions (e.g., Ca 2+ , Mg 2+ , NH 4 + , NO 3 -, SO 4 -), halide ions (e.g., Cl-, Br-) and natural organic matter, showing high robustness for organoarsenic removal under complicated water matrices. Overall, this study shed light on the significance of Mn(III) to the fate of organoarsenics in manganese-rich environments, and demonstrated the promising potential of Mn(III)-based strategies to achieve targeted decontamination in water/wastewater purification., 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.)

A Mn-based nanozyme, Mn-uNF/Si, with excellent alkali phosphatase-like activity was designed by in-situ growth of ultrathin Mn-MOF on the surface of silicon spheres, and implemented as an effective solid Lewis-Brønsted acid catalyst for broad-spectrum dephosphorylation. H 2 18 O-mediated GC-MS studies confirmed the cleavage sites and the involvement of H 2 O in the new bonds. DRIFT NH 3 -IR and in-situ ATR-FTIR confirmed the coexistence of Lewis-Brønsted acid sites and the adjustment of adsorption configurations at the interfacial sites. In addition, a green transformation route of "turning waste into treasure" was proposed for the first time ("OPs→PO 4 3- →P food additive") using edible C. reinhardtii as a transfer station. By alkali etching of Mn-uNF/Si, a nanozyme Mn-uNF with laccase-like activity was obtained. Intriguingly, glyphosate exhibits a laccase-like fingerprint-like response (+,-) of Mn-uNF, and a non-enzyme amplified sensor was thus designed, which shows a good linear relationship with Glyp in a wide range of 0.49-750 μM, with a low LOD of 0.61 μM, as well as high selectivity and anti-interference ability under the co-application of phosphate fertilizers and multiple pesticides. This work provides a controllable methodology for the design of bifunctional nanozymes, which sheds light on the highly efficient green transformation of OPs, and paves the way for the selective recognition and quantification of glyphosate. Mechanistically, we also provided deeper insights into the structure-activity relationship at the atomic scale., 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. This paper is new, neither the entire paper nor any part of its content has been published or has been accepted elsewhere. It is not being submitted to any other journal. We declare that all the authors are aware of the submission and agree to its publication in this journal., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nitric oxide (NO) is a signaling molecule that not only appears in the very early stage of inflammatory disease but also persists in chronic conditions. Its detection in vivo can, therefore, potentially enable early disease detection and treatment monitoring. Due to its transient nature and low abundance, however, noninvasive and deep-tissue imaging of NO dynamics is challenging. In this study, we present a magnetic resonance imaging (MRI) contrast agent based on a manganese porphyrin for specific imaging of NO. This agent is activated by NO, binds to tissue protein, accumulates so long as NO is actively produced, and confers a substantial bright contrast on T 1 -weighted MRI. In vitro tests confirm the specificity of activation by NO over other reactive oxygen or nitrogen species, absence of inflammation induced by the contrast agent, and sensitivity to NO levels in the tens of micromolar. In vivo demonstration in a mouse model of stress-induced acute myocardial inflammation revealed an over 2.2-times increase in T 1 reduction in the inflamed heart compared to a healthy heart. This new NO-activatable T 1 contrast agent holds the potential to provide early diagnosis of inflammatory disease, characterize different stages of inflammation, and ultimately guide the design of novel anti-inflammation therapeutics.

Organic contaminants with lower Hammett constants are typically more prone to being attacked by reactive oxygen species (ROS) in advanced oxidation processes (AOPs). However, the interactions of an organic contaminant with catalytic centers and participating ROS are complex and lack an in-depth understanding. In this work, we observed an abnormal phenomenon in AOPs that the degradation of electron-rich phenolics, such as 4-methoxyphenol, acetaminophen, and 4-presol, was unexpectedly slower than electron-deficient phenolics in a Mn(II)/nitrilotriacetic acid/peroxymonosulfate (Mn(II)/NTA/PMS) system. The established quantitative structure-activity relationship revealed a volcano-type dependence of the degradation rates on the Hammett constants of pollutants. Leveraging substantial analytical techniques and modeling analysis, we concluded that the electron-rich phenolics would inhibit the generation of both primary (Mn(III)NTA) and secondary (Mn(V)NTA) high-valent manganese species through complexation and competition effects. Specifically, the electron-rich phenolics would form a hydrogen bond with Mn(II)/NTA/PMS through outer-sphere interactions, thereby reducing the electrophilic reactivity of PMS to accept the electron transfer from Mn(II)NTA, and slowing down the generation of reactive Mn(III)NTA. Furthermore, the generated Mn(III)NTA is more inclined to react with electron-rich phenolics than PMS due to their higher reaction rate constants (8314 ± 440, 6372 ± 146, and 6919 ± 31 M -1 s -1 for 4-methoxyphenol, acetaminophen, and 4-presol, respectively, as compared with 671 M -1 s -1 for PMS). Consequently, the two-stage inhibition impeded the generation of Mn(V)NTA. In contrast, the complexation and competition effects are insignificant for electron-deficient phenolics, leading to declined reaction rates when the Hammett constants of pollutants increase. For practical applications, such complexation and competition effects would cause the degradation of electron-rich phenolics to be more susceptible to water matrixes, whereas the degradation of electron-deficient phenolics remains largely unaffected. Overall, this study elucidated the intricate interaction mechanisms between contaminants and reactive metal species at both the electronic and kinetic levels, further illuminating their implications for practical treatment.

Leveraging the versatile redox behavior of transition metal complexes with heterocyclic ligands offers significant potential for discovering new anticancer therapeutics. This study presents a systematic investigation of a pyridinecarboxaldimine ligand (PyIm) with late 3d-transition metals inhibiting cancer cell proliferation and the mechanism of action. Synthesis and thorough characterization of authentic metal complexes of redox-active late 3d-transition metals enabled the validation of antiproliferative activity in liver cancer cells. Notably, (PyIm) 2 Mn(II) ( 1 ) and (PyIm) 2 Cu(II) ( 5 ) complexes exhibited a good inhibitory profile against liver cancer cells (EC 50 : 4.0 μM for 1 and 1.7 μM for 5 ) with excellent selectivity over normal kidney cells (Selectivity index, SI = 17 for 5 ). Subsequently, evaluation of these complexes in cancers cell lines from four different sites of origin (liver, breast, blood, and bone) demonstrated a predominant selectivity to liver and a moderate selectivity to breast cancer and leukemia cells over the normal kidney cells. The mechanism of action studies highlighted no expected DNA damage in cells, rather, the enhancement of extracellular and intracellular reactive oxygen species (ROS) resulting in mitochondrial damage leading to oxidative cell death in cancer cells. Notably, these complexes potentiated the antiproliferative effect of commercially used cancer therapeutics (cisplatin, oxaliplatin, doxorubicin, and dasatinib) in liver cancer cells. These findings position redox-active metal complexes for further evaluation as promising candidates for developing anticancer therapeutics and combination therapies.

We explore the potential of fluorine-containing small Mn 2+ chelates as alternatives to perfluorinated nanoparticles, widely used as 19 F MRI probes. In MnL1, the cyclohexanediamine skeleton and two piperidine rings, involving each a metal-coordinating amide group and an appended CF 3 moiety, provide high rigidity to the complex. This allows for good control of the Mn-F distance (r MnF =8.2±0.2 Å determined from 19 F relaxation data), as well as for high kinetic inertness (a dissociation half-life of 1285 h is estimated for physiological conditions). The paramagnetic Mn 2+ leads to a ~150-fold acceleration of the longitudinal 19 F relaxation, with moderate line-broadening effect, resulting in T 2 /T 1 ratios of 0.8 (9.4 T). Owing to its inner sphere water molecule, MnL1 is a good 1 H relaxation agent as well (r 1 =5.36 mM -1  s -1 at 298 K, 20 MHz). MnL1 could be readily visualized in 19 F MRI by using fast acquisition techniques, both in phantom images and living mice following intramuscular injection, with remarkable signal-to-noise ratios and short acquisition times. While applications in targeted imaging or cell therapy monitoring require further optimisation of the molecular structure, these results argue for the potential of such small, monohydrated and fluorinated Mn 2+ complexes for combined 19 F and 1 H MRI detection., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Scaffolds play a crucial role in bone tissue engineering to support the defect area through bone regeneration and defect reconstruction. Promising tissue regeneration without negative repercussions and avoidance of the lifelong presence inside the body make bioresorbable metals prosper in the field of regenerative medicine. Recently, Zn and its alloys have emerged as promising biodegradable materials for their moderate degradation rate and satisfactory biocompatibility. Nevertheless, it is very challenging for cells to adhere and grow over the Zn surface alone, which influences the tissue-implant integration. In this study, an attempt has been made to systematically investigate the bioactivity responses in terms of in vitro hemocompatibility, cytotoxicity, antibacterial activity, and in vivo biocompatibility of newly developed Zn-2Cu-0.5Mn/Mg alloy scaffolds with different surface roughness. The rough surface of Zn-2Cu-0.5Mg shows the highest degradation rate of 0.16 mm/yr. The rough surface exhibits a prominent role in the adsorption of protein, further enhancing cell adhesion. Concentration-dependent alloy extract shows the highest cell proliferation for 12.5% of the extract with a maximum cell viability of 101% in Zn-2Cu-0.5Mn and 108% in Zn-2Cu-0.5Mg after 3 d. Acceptable hemolysis percentages (less than 5%) with promising anticoagulation properties are observed for all of the conditions. Enhanced antibacterial ( Staphylococcus aureus and Escherichia coli ) activity due to a significant effect of ions illustrates the maximum killing effect on the bacterial colony for the rough Zn-2Cu-0.5Mg alloy. In addition, it is observed that for rough Zn-2Cu-0.5Mn/Mg alloys, the inflammatory response is minimal after subcutaneous implantation, and neo-bone tissue forms in the defect areas of the rat femur with satisfactory biosafety response. The osseointegration property of the Zn-2Cu-0.5Mg alloy is comparable to that of the Zn-2Cu-0.5Mn alloy. Therefore, the rough surface of the Zn-2Cu-0.5Mg alloy has the potential to enhance biocompatibility and promote better osseointegration activity with host tissues for various biomedical applications.

Chemodynamic therapy (CDT) is a new method for cancer treatment that produces highly toxic reactive oxygen species (ROS) in the tumor microenvironment to induce cancer cell apoptosis or necrosis. However, the therapeutic effect of CDT is often hindered by intracellular H 2 O 2 deficiency and the activity of antioxidants such as glutathione (GSH). In this study, a nano-catalyst HCM was developed using a self-assembled Cu/Mn-doped metal-organic framework, and its surface was modified with hyaluronic acid to construct a tumor-targeting CDT therapeutic agent with improved the efficiency and specificity. Three substances HHTP (2, 3, 6, 7, 10, 11-hexahydroxybenzophenanthrene), Cu 2+ , and Mn 2+ were shown to be decomposed and released under weakly acidic conditions in tumor cells. HHTP produces exogenous H 2 O 2 in the presence of oxygen to increase the H 2 O 2 content in tumors, Cu 2+ reduces GSH content and generates Cu + in the tumor, and Cu + and Mn 2+ catalyze H 2 O 2 to produce ∙OH in a Fenton-like reaction. Together, these three factors change the tumor microenvironment and improve the efficiency of ROS production. HCM showed selective and efficient cytotoxicity to cancer cells, and could effectively inhibit tumor growth in vivo , indicating a good CDT effect., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Herein, a direct in situ alkaline phosphatase (ALP)-labeled luminescent nanoimmunoassay platform was constructed using Mn 2+ -triggered aggregation-induced emission transformation of levodopa fluorescent copolymer (LFC) nanoparticles. Using cardiac troponin I (cTn I) as the model antigen, the proposed nanoimmunosensor has been applied to detect cTn I in clinical samples with satisfactory results.

By self-assembly of MnCl 2 and arginine under alkaline conditions, ultra-small MnArg nanoparticles were successfully constructed as oxidase (OXD) mimics for intelligent detection of the Ginkgo toxin 4'-O-methylpyridoxal (MPN). The obtained MnArg nanozymes possessed excellent OXD-like activity and thermal stability. Based on the inhibitory effect of MPN for the catalytic activity of MnArg, this system was utilized for the colorimetric sensing of MPN with a low limit of detection (LOD) of 2.16 µg mL -1 . The detection  system exhibited good selectivity against other potential interferents. FTIR data showed that the presence of MPN binds with MnArg and shields the active sites, thereby interfering with the oxidase-like activity. Combined with a smartphone and the ColorMax software, this nanozyme-based intelligent detection platform could effectively detect MPN with a LOD of 2.1 µg mL -1 . Our MnArg nanozyme-based system was applied to detect real ginkgo nut samples with recoveries of 92.4-108.7%, and the relative standard deviations were less than 0.7%. This work may promote the development of novel nanozymes and expand their applications in the field of food safety detection., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The irradiated tumor itself represents an opportunity to establish endogenous in situ vaccines. However, such in situ cancer vaccination (ISCV) triggered by radiation therapy (RT) alone is very weak and hardly elicits systemic anticancer immunity. In this study, we develop two-dimensional risedronate-manganese nanobelts (RMn-NBs) as an adjuvant for RT to address this issue. RMn-NBs exhibit good T 2 magnetic resonance imaging performance and enhanced Fenton-like catalytic activity, which induces immunogenic cell death. RMn-NBs can inhibit the HIF-1α/VEGF axis to empower RT and synchronously activate the cGAS/STING pathway for promoting the secretion of type I interferon, thereby boosting RT-triggered ISCV and immune checkpoint blockade therapy against primary and metastatic tumors. RMn-NBs as a nano-adjuvant for RT show good biocompatibility and therapeutic efficacy, presenting a promising prospect for cancer radiotherapy and immunotherapy., (© 2024. The Author(s).)

Sonocatalytic therapy (SCT) has emerged as a promising noninvasive modality for tumor treatment but is hindered by the insufficient generation of ultrasound-induced reactive oxygen species (ROS) and the hypoxic tumor microenvironments. Herein, we fabricated a carbon nanoframe-confined N-coordinated manganese single-atom sonocatalyst with a five-coordinated structure (MnN 5 SA/CNF) using a phthalocyanine-mediated pyrolysis strategy. The precise coordination structure was identified by synchrotron X-ray absorption fine structure analyses. The MnN 5 SA/CNF exhibits superior and nonoxygen-dependent sonocatalytic activity owing to the optimized coordination structure and cavitation effect enhanced by defects. Additionally, density functional theory studies reveal that the five-coordination structure downshifts the d-band center of Mn from -0.547 to -0.829 eV and enhances the desorption capacity for oxygen-containing intermediates, thus accelerating the catalytic process. Finally, the as-synthesized MnN 5 SA/CNF demonstrates a significantly enhanced antitumor effect through mitochondrial apoptosis in an orthotopic breast cancer mouse model. This work explores the potential of SAzymes-supported biomedical interventions by leveraging enzymatic activity with sonocatalytic properties.

We conducted an in-depth exploration of the in vitro activities of the dinuclear Mn 2 L 2 Ac and Mn 2 L 2 complexes (where HL=2-{[di(2-pyridyl)methylamino]-methyl}phenol), possessing dual superoxide dismutase (SOD) and catalase (CAT) activity. We investigated these complexes both individually and in conjunction with various Pt(II)-complexes, either as mixtures or as the Mn 2 -Pt adducts. Our findings revealed a notable up to 50 % enhancement in the viability of healthy human breast cells, contrasted with a viability decrease as low as 50 % in breast cancer cells upon combined treatments with Mn 2 SOD mimics and Pt(II) complexes. Specifically, we synthesized and characterized the self-assembled Mn 2 -Pt adducts (isolated Mn 2 L 2 Pt and in situ Mn 2 L 2 Pt'), linking Mn 2 L 2 -core with the carboxylate group of PtDAPCl 2 (dichloro(2,3-diaminopropionic acid) platinum(II)). The SOD activity of the isolated Mn 2 L 2 Pt adduct (k SOD =1.7×10 7  M -1  s -1 ) remained intact. Through in vitro cell viability assessments, ROS levels, cellular Mn uptake and proteomics measurements, we elucidated key mechanisms underlying the observed biological effects. We demonstrated that Mn 2 -containing formulations predominantly target mitochondrial processes, differently affecting the proteome of cancerous and healthy cells. They induced downregulation of H 2 S signaling and expression of mitochondrial complex I and III, as well as increased oxidative phosphorylation pathways and upregulation of EGFR in cancer cells. In contrast, healthy cells showed a decrease in EGFR expression and a moderate enrichment in oxidative phosphorylation pathways., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

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.

Green synthesized iron/manganese nanoparticles (Fe/Mn NPs), acted as an exogenous promoter to enhance the lignin-degrading bacteria Comamonas testosteroni FJ17 resulting in more efficient removal of bisphenol A (BPA). Batch experiments demonstrated that removal efficiency of BPA via cells at a BPA concentration of 10 mg·L -1 increased by 20.9 % when exposed to 100 mg·L -1 Fe/Mn NPs after 48 h (93.63 %) relative to an unexposed control group (72.70 %). TEM and 3D-EEM analysis confirmed that the cell membrane thickness increased from 47 to 80 nm under Fe/Mn NPs exposure, and the TB-EPS secretion was promoted. Meanwhile, Fe/Mn NPs facilitated greater electron transfer capacity of c-cytochrome (0.55 V reduction peak) and an unknown cytochrome substance (0.7 V oxidation peak) on the surface of cells. Studies of the effect of Fe/Mn NPs on both the growth and activity of laccase cells showed that both biomass and laccase secretion increased significantly during the logarithmic growth period (6-36 h). LC-MS analysis and toxicity assessment indicated that Fe/Mn NPs decreased the degradation time of BPA and efficiently reduced the toxicity of its by-products. Transcriptomic analysis revealed 315 up-regulation of the key genes associated with energy supply, membrane translocation, and metabolic pathways upon exposure to Fe/Mn NPs. Such as MFS transporter (2.27-fold), diguanylate cyclase (1.76-fold) and protocatechuate-3,4-dioxygenase (1.62-fold). Overall, Fe/Mn NPs accelerated proliferation by enhancing metabolic capacity and nutrient transport processes, which serves to improve the efficiency of BPA removal., 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.)

Tumor immunotherapy has gained more and more attention in tumor treatment. However, the accumulation of lactic acid in tumor tissue inhibits the response of immune cells to form an immunosuppressive microenvironment (ISME). To reverse the ISME, an acid-responsive nanoplatform (termed as MLLN@HA) is reported for synergistically enhanced tumor immunotherapy. MLLN@HA is constructed by the co-loading of lactate oxidase (LOX) and DNA repair inhibitor (NU7441) in a manganese-doped layered double hydroxide (Mn-LDH), and then modified with hyaluronic acid (HA) for tumor-targeted delivery. After endocytosis by tumor cells, MLLN@HA decomposes and releases LOX, NU7441 and Mn 2+ ions in the acidic tumor microenvironment. The released LOX catalyzes the conversion of lactic acid into hydrogen peroxide (H 2 O 2 ), which not only alleviates the ISME, but also provides reactants for the Mn 2+ -mediated Fenton-like reaction to enhance chemodynamic therapy (CDT). Released NU7441 prevents CDT-induced DNA damage from being repaired, thereby increasing double-stranded DNA (dsDNA) fragments within tumor cells. Importantly, the released Mn 2+ ions enhance the sensitivity of cyclic GMP-AMP synthase (cGAS) to dsDNA fragments, and activate the stimulator of interferon genes (STING) to induce an anti-tumor immune response. Such an orchestrated immune-boosting strategy ultimately achieves effective tumor growth inhibition and prevents tumor lung metastasis. STATEMENT OF SIGNIFICANCE: To improve the efficacy of tumor immunotherapy, an innovative acid-responsive MLLN@HA nanoplatform was developed for synergistically enhanced tumor immunotherapy. The MLLN@HA actively targets to tumor cells through the interaction of HA with CD44, and then degrades to release LOX, NU7441 and Mn 2+ ions in the acidic tumor microenvironment. The released LOX generates H 2 O 2 for the Mn 2+ -mediated Fenton reaction and reverses the ISME by consuming lactate. NU7441 prevents DNA damage repair, leading to an increased concentration of free DNA fragments, while Mn 2+ ions activate the cGAS-STING pathway, enhancing the systemic anti-tumor immune response. The orchestrated immune-boosting nanoplatform effectively inhibits tumor growth and lung metastasis, presenting a promising strategy for cancer treatment., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The highly immunosuppressive tumor microenvironment (TME) restricts the efficient activation of immune responses. To restore the surveillance of the immune system for robust activation, vast efforts are devoted to normalizing the TME. Here, a manganese-doped layered double hydroxide (Mn-LDH) is developed for potent anti-tumor immunity by reversing TME. Mn-LDH is synthesized via a one-step hydrothermal method. In addition to the inherent proton neutralization capacity of LDH, the introduction of manganese oxide endows LDH with an additional ability to produce oxygen. Mn-LDH effectively releases Mn 2+ and Mg 2+ upon exposure to TME with high levels of H + and H 2 O 2 , which activates synthase-stimulator of interferon genes pathway and maintains the cytotoxicity of CD8 + T cells respectively, achieving a cascade-like role in innate and adaptive immunity. The locally administered Mn-LDH facilitated a "hot" network consisting of mature dendritic cells, M1-phenotype macrophages, as well as cytotoxic and helper T cells, significantly inhibiting the growth of primary and distal tumors. Moreover, the photothermal conversion capacity of Mn-LDH sparks more robust therapeutic effects in large established tumor models with a single administration and irradiation. Overall, this study guides the rational design of TME-modulating immunotherapeutics for robust immune activation, providing a clinical candidate for next-generation cancer immunotherapy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Mn-catalyzed hydroarylation polyaddition of 1-(2-pyrimidinyl)pyrrole (1a) with aromatic diynes is investigated. The use of commercially available MnBr(CO) 5 as a precatalyst under the optimized reaction conditions resulted in a site- and regioselective hydroarylation polyaddition, affording the corresponding poly(arylenevinylene)s (PAVs) with excellent vinylene selectivity. The reaction protocol eliminates the production of stoichiometric amounts of byproducts from the monomers. The nonstoichiometric polyaddition of an excess amount of 1a with aromatic diynes is also demonstrated. The 2-pyrimidinyl substituent promoted the intramolecular transfer of the Mn catalyst walking through the 1a moiety., (© 2024 Wiley‐VCH GmbH.)

In situ vaccine (ISV) can provoke systemic anti-tumor immunity through the induction of immunogenic cell death (ICD). The development of ISV technology has been restricted by the limited and suboptimal ICD driven tumor antigen production which are currently relying on chemo-drugs, photo-/radio-sensitizers, oncolytic-virus and immunostimulatory agents. Herein, a sulfate radical (SO 4 ·- ) based ISV is reported that accomplishes superior tumor immunotherapy dispense from conventional approaches. The ISV denoted as P-Mn-LDH is constructed by intercalating peroxydisulfate (PDS, a precursor of SO 4 ·- ) into manganese layered double hydroxide nanoparticles (Mn-LDH). This design allows the stabilization of PDS under ambient condition, but triggers a Mn 2+ mediated PDS decomposition in acidic tumor microenvironment (TME) to generate in situ SO 4 ·- . Importantly, it is found that the SO 4 ·- radicals not only effectively kill cancer cells, but also induce a necroptotic cell death pathway, leading to robust ICD signaling for eliciting adaptive immunity. Further, the P-Mn-LDH can activate the stimulator of interferon genes (STING) pathway to further boost anti-tumor immunity. Collectively, the P-Mn-LDH based ISV exhibited potent activity in inhibiting tumor growth and lung metastasis. When combined with immune checkpoint inhibitor, significant inhibition of distant tumors is achieved. This study underpins the promise of SO 4 ·- based vaccine technology for cancer immunotherapy., (© 2024 Wiley‐VCH GmbH.)

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).)

Purpose: Due to their long circulation time in the blood, monoclonal antibodies (mAbs) such as trastuzumab, are usually radiolabeled with long-lived positron emitters for the development of agents for Positron Emission Tomography (PET) imaging. Manganese-52 ( 52 Mn, t 1/2  = 5.6 d, β +  = 29.6%, E(β ave ) = 242 keV) is suitable for imaging at longer time points providing a complementary technique to Zirconium-89 ( 89 Zr, t 1/2  = 3.3 d, β +  = 22.7%, E(β ave ) = 396 keV)) because of its long half-life and low positron energy. To exploit these properties, we aimed to investigate suitable bifunctional chelators that could be readily conjugated to antibodies and labeled with 52 Mn under mild conditions using trastuzumab as a proof-of-concept., Procedures: Trastuzumab was incubated with S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA), 1-Oxa-4,7,10-tetraazacyclododecane-5-S-(4-isothiocyantobenzyl)-4,7,10-triacetic acid (p-SCN-Bn-Oxo-DO3A), and 3,6,9,15-tetraazabicyclo[9.3.1] pentadeca-1(15),11,13-triene-4-S-(4-isothiocyanatobenzyl)-3,6,9-triacetic acid (p-SCN-Bn-PCTA) at a tenfold molar excess. The immunoconjugates were purified, combined with [ 52 Mn]MnCl 2 at different ratios, and the labeling efficiency was assessed by iTLC. The immunoreactive fraction of the radiocomplex was determined through a Lindmo assay. Cell studies were conducted in HER2 + (BT474) and HER2- (MDA-MB-468) cell lines followed by in vivo studies., Results: Trastuzumab-Oxo-DO3A was labeled within 30 min at 37 °C with a radiochemical yield (RCY) of 90 ± 1.5% and with the highest specific activity of the chelators investigated of 16.64 MBq/nmol. The labeled compound was purified with a resulting radiochemical purity of > 98% and retained a 67 ± 1.2% immunoreactivity. DOTA and PCTA immunoconjugates resulted in < 50 ± 2.5% (RCY) with similar specific activity. Mouse serum stability studies of [ 52 Mn]Mn-Oxo-DO3A-trastuzumab showed 95% intact complex for over 5 days. Cell uptake studies showed higher uptake in HER2 + (12.51 ± 0.83% /mg) cells compared to HER2- (0.85 ± 0.10%/mg) cells. PET images of mice bearing BT474 tumors showed high tumor uptake that was consistent with the biodistribution (42.02 ± 2.16%ID/g, 14 d) compared to MDA-MB-468 tumors (2.20 ± 0.80%ID/g, 14 d). Additionally, both models exhibited low bone uptake of < 1% ID/g., Conclusion: The bifunctional chelator p-SCN-Bn-Oxo-DO3A is promising for the development of 52 Mn radiopharmaceuticals as it was easily conjugated, radiolabeled at mild conditions, and illustrated stability for a prolonged duration both in vitro and in vivo. High-quality PET/CT images of [ 52 Mn]Mn-Oxo-DO3A-trastuzumab were obtained 14 d post-injection. This study illustrates the potential of [ 52 Mn]Mn-Oxo-DO3A for the evaluation of antibodies using PET imaging., (© 2024. The Author(s).)

Surface-enhanced Raman scattering (SERS) imaging integrating photothermal and photodynamic therapy (PTT/PDT) is a promising approach for achieving accurate diagnosis and effective treatment of cancers. However, most available Raman reporters show multiple signals in the fingerprint region, which overlap with background signals from cellular biomolecules. Herein, a 4T1 cell membrane-enveloped gold nanorods-manganese porphyrins system (GMCMs) is designed and successfully fabricated as a biomimetic theranostic nanoplatform. Manganese porphyrins are adsorbed on the surface of Au nanorods via the terminal alkynyl group. Cell membrane encapsulation protects the manganese porphyrins from falling off the gold nanorods. The biomimetic GMCMs confirm specific homologous targeting to 4T1 cells with good dispersibility, excellent photoacoustic (PA) imaging properties, and preferable photothermal and 1 O 2 generation performance. GMCMs exhibit distinct SERS signals in the silent region without endogenous biomolecule interference both in vitro and in vivo. Manganese ions could not only quench the fluorescence of porphyrins to enhance the SERS imaging effect but also deplete cellular GSH to increase 1 O 2 yield. Both in vitro and in vivo studies demonstrate that GMCMs effectively eradicate tumors through SERS/PA imaging-guided PTT/PDT. This study provides a feasible strategy for augmenting the Raman imaging effects of the alkynyl group and integrating GSH-depletion to enhance PTT/PDT efficacy., (© 2024 Wiley‐VCH GmbH.)

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.)

Heterogeneous catalytic processes based on zero-valent iron (ZVI) have been developed to treat soil and wastewater pollutants. However, the agglomeration of ZVI reduces its ability to activate persulfate (PS). In this study, a new Fe-Mn@AC activated material was prepared to activated PS to treat oil-contaminated soil, and using the microscopic characterization of Fe-Mn@AC materials, the electron transfer mode during the Fe-Mn@AC activation of PS was clarified. Firstly, the petroluem degradation rate was optimized. When the PS addition amount was 8%, Fe-Mn@AC addition amount was 3% and the water to soil ratio was 3:1, the petroluem degradation rate in the soil reached to the maximum of 85.69% after 96 h of reaction. Then it was illustrated that sulfate and hydroxyl radicals played major roles in crude oil degradation, while singlet oxygen contributed slightly. Finally, the indigenous microbial community structures remaining after restoring the Fe-Mn@AC/PS systems were analyzed. The proportion of petroleum degrading bacteria in soil increased by 23% after oxidation by Fe-Mn@AC/PS system. Similarly, the germination rate of wheat seeds revealed that soil toxicity was greatly reduced after applying the Fe-Mn@AC/PS system. After the treatment with Fe-Mn@AC/PS system, the germination rate, root length and bud length of wheat seed were increased by 54.05%, 7.98 mm and 6.84 mm, respectively, compared with the polluted soil group. These results showed that the advanced oxidation system of Fe-Mn@AC activates PS and can be used in crude oil-contaminated soil 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 Elsevier Inc. All rights reserved.)

The cycling processes of elemental manganese (Mn), including the redox reactions of dissolved Mn(III) (dMn(III)), directly and indirectly influences the biogeochemical processes of many elements. Though increasing evidence indicates the widespread presence of dMn(III) mediates the fate of many elements, its role may be currently underestimated. There is both a lack of clear understanding of the historical research framework of dMn(III) and a systematic overview of its geochemical properties and detection methods. Therefore, the primary aim of this review is to outline the understanding of dMn(III) in multiple fields, including soil science, analytical chemistry, biochemistry, geochemistry, and water treatment, and summarize the formation pathways, species forms, and detection methods of dMn(III) in aquatic systems. This review considers how the characteristics of dMn(III), the intermediate formed in the single-electron reaction processes of Mn(II) oxidation and Mn(IV) reduction, determines its participation in environmental geochemical processes. Its widespread presence in diverse water systems and active redox properties coupling with various elements confirm its significant role in natural elemental geochemistry cycle and artificial water treatment processes. Therefore, further investigation into the role of dissolved Mn(III) in aquatic systems is warranted to unravel unexplored coupled elemental redox reaction processes mediated by dissolved Mn(III), filling in the gaps in our understanding of manganese environmental geochemistry, and providing a theoretical basis for recognizing the role of dMn(III) role in water treatment technologies., 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.)

Manganese hydroxido (Mn-OH) complexes supported by a tripodal N,N',N″-[nitrilotris(ethane-2,1-diyl)]tris(P,P-diphenylphosphinic amido) ([poat] 3- ) ligand have been synthesized and characterized by spectroscopic techniques including UV-vis and electron paramagnetic resonance (EPR) spectroscopies. X-ray diffraction (XRD) methods were used to confirm the solid-state molecular structures of {Na 2 [Mn II poat(OH)]} 2 and {Na[Mn III poat(OH)]} 2 as clusters that are linked by the electrostatic interactions between the sodium counterions and the oxygen atom of the ligated hydroxido unit and the phosphinic (P=O) amide groups of [poat] 3- . Both clusters feature two independent monoanionic fragments in which each contains a trigonal bipyramidal Mn center that is comprised of three equatorial deprotonated amide nitrogen atoms, an apical tertiary amine, and an axial hydroxido ligand. XRD analyses of {Na[Mn III poat(OH)]} 2 also showed an intramolecular hydrogen bonding interaction between the Mn III -OH unit and P=O group of [poat] 3- . Crystalline {Na[Mn III poat(OH)]} 2 remains as clusters with Na + ---O interactions in solution and is unreactive toward external substrates. However, conductivity studies indicated that [Mn III poat(OH)] - generated in situ is monomeric and reactivity studies found that it is capable of cleaving C-H bonds, illustrating the importance of solution-phase speciation and its direct effect on chemical reactivity. Synopsis: Manganese-hydroxido complexes were synthesized to study the influence of H-bonds in the secondary coordination sphere and their effects on the oxidative cleavage of substrates containing C-H bonds., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Strontium, cobalt, and manganese ions are present in the composition of bone and useful for bone metabolism, even when combined with calcium phosphate in the composition of biomaterials. Herein we explored the possibility to include these ions in the composition of apatitic materials prepared through the cementitious reaction between ion-substituted calcium phosphate dibasic dihydrate, CaHPO 4 ·2H 2 O (DCPD) and tetracalcium phosphate, Ca 4 (PO 4 ) 2 O (TTCP). The results of the chemical, structural, morphological and mechanical characterization indicate that cobalt and manganese exhibit a greater delaying effect than strontium (about 15 at.%) on the cementitious reaction, even though they are present in smaller amounts within the materials (about 0.8 and 4.5 at.%, respectively). Furthermore, the presence of the foreign ions in the apatitic materials leads to a slight reduction of porosity and to enhancement of compressive strength. The results of biological tests show that the presence of strontium and manganese, as well as calcium, in the apatitic materials cultured in direct contact with human mesenchymal stem cells (hMSCs) stimulates their viability and activity. In contrast, the apatitic material containing cobalt exhibits a lower metabolic activity. All the materials have a positive effect on the expression of Vascular Endothelial Growth Factor (VEGF) and Von Willebrand Factor (vWF). Moreover, the apatitic material containing strontium induces the most significant reduction in the differentiation of preosteoclasts into osteoclasts, demonstrating not only osteogenic and angiogenic properties, but also ability to regulate bone resorption., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Nickel-manganese-cobalt tetragonal spinel ternary oxide nanocomposite (NMC-TSO) was synthesized. It was utilized as an efficient sorbent for the dispersive solid phase microextraction (D-SPμE) without vortexing of cadmium. The analysis of the cadmium was carried out by FAAS. The effective analytical parameters including pH (6) contact times (no vortexing), sample volume (70 mL), eluent volume (3 mL of 2 mol L -1 HCl), linear dynamic ranges (1.07-85.7 μg L -1 ), and re-useability (33) on the D-SPμE efficiency were investigated. The PF, RSD% and LOD of the D-SPμE for cadmium were 23.3, ≤ 2.8% and 0.49 μg L -1 , respectively. The tolerable concentrations of Ca 2+ , Mg 2+ , K + and Na + on Cd(II) were 50,000 mg L -1 , 50,000 mg L -1 , 25,000 mg L -1 and 7500 mg L -1 , respectively. The method was accurated by analysis of food and water certificate reference materials (NW-TMDA-54.6 Lake water, SPS-WW1 121 Batch wastewater, 1573a Tomato Leaves and TORT-3 Lobster Hepatopancreas) and - recovery experiments. The D-SPμE-FAAS method was applied for the cadmium determination in dam water, wastewater, river water, well water, sea water, tea, cacao, nut, bitter chocolate, rice, leek, cinnamon and parsley., 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.)

Reactive oxygen species (ROS) that are overproduced in certain tumors can be considered an indicator of oxidative stress levels in the tissue. Here, we report a magnetic resonance imaging (MRI)-based probe capable of detecting ROS levels in the tumor microenvironment (TME) using ROS-responsive manganese ion (Mn 2+ )-chelated, biotinylated bilirubin nanoparticles (Mn@bt-BRNPs). These nanoparticles are disrupted in the presence of ROS, resulting in the release of free Mn 2+ , which induces T1-weighted MRI signal enhancement. Mn@BRNPs show more rapid and greater MRI signal enhancement in high ROS-producing A549 lung carcinoma cells compared with low ROS-producing DU145 prostate cancer cells. A pseudo three-compartment model devised for the ROS-reactive MRI probe enables mapping of the distribution and concentration of ROS within the tumor. Furthermore, doxorubicin-loaded, cancer-targeting ligand biotin-conjugated Dox/Mn@bt-BRNPs show considerable accumulation in A549 tumors and also effectively inhibit tumor growth without causing body weight loss, suggesting their usefulness as a new theranostic agent. Collectively, these findings suggest that Mn@bt-BRNPs could be used as an imaging probe capable of detecting ROS levels and monitoring drug delivery in the TME with potential applicability to other inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:S.J. declares a financial interest in BiliX and ToolBio as a cofounder as well as a scientific advisory board member. However, these companies did not support the aforementioned research and currently has no rights to any technology or intellectual property developed as part of this research. The rest of the authors declare no competing financial interests., (Copyright © 2024 Elsevier Ltd. 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 a versatile transition element with diverse oxidation states and significant biological importance. Mn-based nanozymes have emerged as promising catalysts in various applications. However, the direct use of manganese oxides as oxidase mimics remains limited and requires further improvement. In this study, we focus on hydroxylated manganese (MnOOH), specifically the layered form β-MnOOH which exhibits unique electronic and structural characteristics. The two-dimensional β-MnOOH nanosheets were synthesized through a hydrothermal approach and showed remarkable oxidase-like activity. These nanosheets effectively converted the oxidase substrate, 3,3',5,5'-tetramethylbenzidine (TMB), into its oxidized form by initiating the conversion of dissolved oxygen into ·O 2 - , 1 O 2 and ·OH. However, in the presence of L-cysteine (L-Cys), the catalytic activity of β-MnOOH was significantly inhibited, enabling highly sensitive detection of L-Cys. This sensing strategy was successfully applied for smartphone-based L-Cys assay, offering potential utility in the diagnosis of Cys-related diseases. The exploration of layered β-MnOOH nanosheets as highly active oxidase mimics opens up new possibilities for catalytic and biomedical applications., 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.)

The Fe-Mn alloys are potential candidates for biodegradable implant applications. However, the very low degradation rates of Fe-Mn alloys in the physiological environment are a major disadvantage. In this study, the degradation rate of a Fe-20Mn alloy was improved using the groove pressing (GP) technique. Hot rolled sheets of 2 mm thickness were subjected to GP operation at 1000°C. Uniform fine-grained (UFG) Fe-Mn alloys were obtained using the GP technique. The influence of GP on the microstructure, mechanical properties, degradation behavior in simulated body fluid (SBF), surface wettability, biomineralization, and cytocompatibility was investigated and compared to the annealed (A Fe-Mn) and rolled (R Fe-Mn) sample. The groove-pressed Fe-Mn (G Fe-Mn) alloy had a grain size of approximately 40 ± 16 μm whereas the A Fe-Mn and R Fe-Mn samples had grain sizes of 303 ± 81 and 117 ± 14.5 μm, respectively. Enhanced strength and elongation were also observed with the G Fe-Mn sample. The potentiodynamic polarization test showed the highest I corr , lowest polarization resistance, and lowest E corr for the G Fe-Mn sample among all other samples indicating its higher degradation rate. The weight loss data from immersion tests also shows that the percentage of weight loss increases with time indicating the accelerated degradation behavior of the sample. The static immersion test showed an enhancement in weight loss of 0.46 ± 0.02% and 1.02 ± 0.05% for R Fe-Mn and G Fe-Mn samples, respectively, than A Fe-Mn sample (0.31 ± 0.03%) after 56 days in immersion in SBF. The greater biomineralization tendency in UFG materials is confirmed by the G Fe-Mn sample's stronger hydroxyapatite deposition. When compared to the A Fe-Mn and R Fe-Mn samples, the G Fe-Mn sample has a better wettability, which promotes higher cell adhesion and vitality, showing higher biocompatibility. This study demonstrates that Fe-20Mn processed by GP has potential applications for the manufacture of biodegradable metallic implants., (© 2024 Wiley Periodicals LLC.)

Rationale: Alzheimer's disease (AD) is hallmarked by amyloid-β (Aβ) plaques and hyperphosphorylated tau (p-tau) neurofibrillary tangles. While Aβ-centric therapies have shown promise, the complex pathology of AD requires a multifaceted therapeutic approach. The weak association between Aβ levels and cognitive decline highlights the need for alternative theranostic strategies. Currently, oxidative stress and tau hyperphosphorylation are now recognized as critical pathological events in AD. Thus, therapies that concurrently attenuate oxidative stress damage and inhibit tau pathology hold great potential for AD treatment. Methods: Herein, a multifunctional neuron-targeted nanocomposite is devised to realize dual imaging-guided AD therapy, integrating the inhibition of tau pathology and reactive oxygen species (ROS)-neutralizing biofunctions. The construction of the nanocomposite incorporates polyphenolic antioxidants tannic acid (TA)-based nanoparticles carrying manganese ions (Mn 2+ ) and fluorescent dye IR780 iodide (IR780), coupled with a neuron-specific TPL peptide. The resulting IR780-Mn@TA-TPL nanoparticles (NPs) are comprehensively evaluated in both in vitro and in vivo AD models to assess their imaging capabilities and therapeutic efficacy. Results: The nanocomposite facilitates Mn-enhanced magnetic resonance (MR) imaging and near-infrared (NIR) fluorescence imaging. It effectively neutralizes toxic ROS and reduces tau hyperphosphorylation and aggregation. In AD rat models, the nanocomposite restores neuronal density in the hippocampus and significantly improves spatial memory. Conclusions: Such a neuron‑targeting multifunctional nanocomposite represents a potential theranostic strategy for AD, signifying a shift towards bimodal imaging-guided treatment approaches., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The demetallation reaction of sulfanyl magnesium(II) porphyrazine with N-ethylphthalimide substituents, followed by remetallation with manganese(II) salts, yields the corresponding manganese(III) derivative (Pz3) with high efficiency. This novel manganese(III) sulfanyl porphyrazine was characterized by HPLC and analyzed using UV-Vis, MS, and FT-IR spectroscopy. Electrochemical experiments of Pz3 conducted in dichloromethane revealed electrochemical activity of the new complex due to both manganese and N-ethylphthalimide substituents redox transitions. Subsequently, Pz3 was deposited on multiwalled carbon nanotubes (MWCNTs), and this hybrid material was then applied to glassy carbon electrodes (GC). The resulting hybrid electroactive electrode material, combining manganese(III) porphyrazine with MWCNTs, showed a significant decrease in overpotential of H 2 O 2 oxidation compared to bare GC or GC electrodes modified with only carbon nanotubes (GC/MWCNTs). This improvement, attributed to the electrocatalytic performance of Mn 3+ , enabled linear response and sensitive detection of H 2 O 2 at neutral pH. Furthermore, a glucose oxidase (GOx)-containing biosensing platform was developed by modifying the prepared GC/MWCNT/Pz3 electrode for the electrochemical detection of glucose. The bioelectrode incorporating the newly designed Pz3 exhibited good activity in the presence of glucose, confirming effective electronic communication between the Pz3, GOx and MWCNT surface. The linear range for glucose detection was 0.2-3.7 mM.

A covalently bonded hexanuclear neutral complex, [Mn 6 (μ 3 -O) 2 (3-MeO-salox) 6 (OAc) 2 (H 2 O) 4 ] (1), has been synthesized and characterized by single crystal X-ray diffraction analysis along with IR and HRMS studies. Complex 1 has been found to selectively interact with human serum albumin (HSA), a model transport protein. The interaction of 1 with HSA was investigated by monitoring the change in the absorbance value of HSA at λ = 280 nm with increasing concentration of 1. Likewise, fluorescence titrations were carried out under two conditions: (i) titration of a 5 μM solution of complex 1 with the gradual addition of HSA, showing a ∼9-fold fluorescence intensity enhancement at 424 nm, upon excitation at 300 nm; and (ii) upon excitation at 295 nm, titration of 5 μM HSA solution with the incremental addition of complex 1, showing a quenching of fluorescence intensity at 334 nm, with simultaneous development of a new emission band at 424 nm. A linear form of the Stern-Volmer equation gives K SV = 9.77 × 10 4 M -1 and the Benesi-Hildebrand plot yields the binding constant as K BH = 1.98 × 10 5 M -1 at 298 K. The thermodynamic parameters, Δ S °, Δ H °, and Δ G °, were estimated by using the van't Hoff relationship which infer the major contribution of hydrophobic interactions between HSA and 1. It was observed that quenching of HSA emission arises mainly through a dynamic quenching mechanism as indicated by the dependence of average lifetime 〈 τ 〉 on the concentration of 1. The changes in the CD (circular dichroism) spectral pattern of HSA in the presence of 1 clearly establish the variation of HSA secondary structure on interaction with 1. The most probable interaction region in HSA for 1 was determined from molecular docking studies which establish the preferential trapping of 1 in the subdomain IIA of site I in HSA and substantiated by the results of site-specific marker studies. Complex 1 was further evaluated for its antiproliferative effects in lung cancer A549 cells, which strictly inhibits the growth of the cells in both 2D and 3D mammospheres, indicating its potential application as an anticancer drug.

Crevice corrosion at the implantation sites cannot be neglected in clinical applications of biodegradable zinc alloys as implants. In this study, a crevice corrosion protocol was designed to investigate the crevice corrosion behavior of the Zn-0.45Mn-0.2Mg (ZMM42) alloy for the first time, by varying crevice thicknesses in simulated body fluid (SBF) through immersion and electrochemical analysis. The results indicated that the ZMM42 alloy was susceptible to crevice corrosion in the range from 0.03 mm to 0.2 mm. When the crevice thickness was 0.05 mm, the crevice corrosion of the specimen became more severe compared to other thicknesses.

The photosynthetic oxygen-evolving center (OEC) is a unique Mn 4 CaO 5 -cluster that catalyses water splitting into electrons, protons, and dioxygen. Precisely structural and functional mimicking of the OEC is a long-standing challenge and pressingly needed for understanding the structure-function relationship and catalytic mechanism of O-O bond formation. Herein we report two simple and robust artificial Mn 3 Ce 2 O 5 -complexes that display a remarkable structural similarity to the OEC in regarding of the ten-atom core (five metal ions and five oxygen bridges) and the alkyl carboxylate peripheral ligands. This Mn 3 Ce 2 O 5 -cluster can catalyse the water-splitting reaction on the surface of ITO electrode. These results clearly show that cerium can structurally and functionally replace both calcium and manganese in the cluster. Mass spectroscopic measurements demonstrate that the oxide bridges in the cluster are exchangeable and can be rapidly replaced by the isotopic oxygen of H 2 18 O in acetonitrile solution, which supports that the oxide bridge(s) may serve as the active site for the formation of O-O bond during the water-splitting reaction. These results would contribute to our understanding of the structure-reactivity relationship of both natural and artificial clusters and shed new light on the development of efficient water-splitting catalysts in artificial photosynthesis., (© 2024 Wiley-VCH GmbH.)

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.