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1.
Sci Rep ; 14(1): 10066, 2024 05 02.
Article En | MEDLINE | ID: mdl-38698009

The global threat of antibiotic resistance has increased the importance of the detection of antibiotics. Conventional methods to detect antibiotics are time-consuming and require expensive specialized equipment. Here, we present a simple and rapid biosensor for detecting ampicillin, a commonly used antibiotic. Our method is based on the fluorescent properties of chitosan-coated Mn-doped ZnS micromaterials combined with the ß-lactamase enzyme. The biosensors exhibited the highest sensitivity in a linear working range of 13.1-72.2 pM with a limit of detection of 8.24 pM in deionized water. In addition, due to the biological specificity of ß-lactamase, the proposed sensors have demonstrated high selectivity over penicillin, tetracycline, and glucose through the enhancing and quenching effects at wavelengths of 510 nm and 614 nm, respectively. These proposed sensors also showed promising results when tested in various matrices, including tap water, bottled water, and milk. Our work reports for the first time the cost-effective (Mn:ZnS)Chitosan micromaterial was used for ampicillin detection. The results will facilitate the monitoring of antibiotics in clinical and environmental contexts.


Ampicillin , Biosensing Techniques , Chitosan , Manganese , Sulfides , Zinc Compounds , Ampicillin/analysis , Ampicillin/chemistry , Chitosan/chemistry , Biosensing Techniques/methods , Zinc Compounds/chemistry , Manganese/chemistry , Sulfides/chemistry , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/chemistry , beta-Lactamases/analysis , beta-Lactamases/metabolism , beta-Lactamases/chemistry , Milk/chemistry , Limit of Detection , Spectrometry, Fluorescence/methods , Fluorescent Dyes/chemistry , Animals
2.
Front Public Health ; 12: 1351479, 2024.
Article En | MEDLINE | ID: mdl-38803810

Background: While increasing concerns arise about the health effects of environmental pollutants, the relationship between blood manganese (Mn) and sarcopenia has yet to be fully explored in the general population. Objective: This study aims to investigate the association between blood manganese (Mn) levels and sarcopenia in adults. Methods: In our study, we evaluated 8,135 individuals aged 18-59 years, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2011 to 2018. We employed generalized additive model (GAM) to discern potential non-linear relationships and utilized the two-piecewise linear regression model to probe the association between blood Mn levels and sarcopenia. Results: After adjusting for potential confounders, we identified non-linear association between blood Mn levels and sarcopenia, with an inflection point at 13.45 µg/L. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 1.006 (0.996 to 1.048) and 1.082 (1.043 to 1.122), respectively. Subgroup analysis showed that the effect sizes of blood Mn on sarcopenia have significant differences in gender and different BMI groups. Conclusion: Our results showed that a reverse U-shaped curve between blood Mn levels and sarcopenia, with an identified the inflection point at blood Mn level of 13.45 µg/L.


Manganese , Nutrition Surveys , Sarcopenia , Humans , Sarcopenia/blood , Male , Adult , Manganese/blood , Female , Middle Aged , Adolescent , Young Adult , Cross-Sectional Studies , United States
3.
Front Immunol ; 15: 1377472, 2024.
Article En | MEDLINE | ID: mdl-38807601

Background: Gastric 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. Methods: Gene 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. Results: GC 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. Conclusion: This 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.


Gene Expression Regulation, Neoplastic , Manganese , Stomach Neoplasms , Tumor Microenvironment , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/immunology , Stomach Neoplasms/therapy , Prognosis , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Biomarkers, Tumor/genetics , Transcriptome , Gene Expression Profiling , Immunotherapy/methods , Male , Female , Databases, Genetic
4.
Biomolecules ; 14(5)2024 May 09.
Article En | MEDLINE | ID: mdl-38785972

Background: Erectile dysfunction (ED) stands out as one of the most prevalent sexual disorders in men, with its incidence progressively escalating with age. As delineated by the International Consultation Committee for Sexual Medicine on Definitions/Epidemiology/Risk Factors for Sexual Dysfunction, the prevalence of ED among men under 40 years is estimated to be within the range of 1-10%. The aim of this study was to determine the relationship between the concentration of bioelements (Zn, Cu, Fe, Cr, Mg, and Mn) in the serum and bone tissue and the concentration of selected hormones in men with and without erectile dysfunction. Materials and methods: The retrospective cohort study included 152 men who underwent total hip arthroplasty for hip osteoarthritis at the Department of Orthopaedic Traumatology and Musculoskeletal Oncology at the Pomeranian Medical University in Szczecin. Certain exclusion criteria were applied to ensure the integrity of the study. These included individuals with diabetes, a history of cancer, alcohol abuse, liver or kidney failure, New York Heart Association (NYHA) class III or IV heart failure, and those taking medications that affect bone metabolism, such as mineral supplements, neuroleptics, chemotherapeutic agents, immunosuppressants, corticosteroids, or antidepressants. Patients with hypogonadism or infertility were excluded from the study. Results: The study showed an association between bioT concentrations and Cu concentrations in both patients with and without erectile dysfunction. A correlation between bioactive testosterone and Cr concentrations was also observed in both groups. Patients with erectile dysfunction showed a relationship between bioT concentration and Zn concentration, TT concentration and Mn concentration, FT concentration and Zn concentration, and E2 concentration and Cr concentration. An analysis of elemental concentrations in bone tissue showed an association between FT and Mg and Mn concentrations, but only in patients with erectile dysfunction. In patients without erectile dysfunction, a correlation was observed between FT and Cu concentrations. A correlation was also observed between bioT concentrations and Mg, Mn, and Zn concentrations, but only in patients with erectile dysfunction. In patients without erectile dysfunction, a correlation was observed between bioT and Cu concentrations. Conclusions: Studying the relationship between the concentration of bioelements (Zn, Cu, Fe, Cr, Mg, and Mn) in the serum and bone tissue and the concentration of selected hormones in men may be important in explaining the etiology of the problem. The study of the concentration of Zn and Cu in bone tissue and serum showed that these two elements, regardless of the place of accumulation, may be related to the concentration of androgens in men.


Arthroplasty, Replacement, Hip , Bone and Bones , Copper , Erectile Dysfunction , Zinc , Humans , Male , Erectile Dysfunction/blood , Middle Aged , Aged , Retrospective Studies , Zinc/blood , Bone and Bones/metabolism , Copper/blood , Aging/blood , Chromium/blood , Magnesium/blood , Iron/blood , Iron/metabolism , Manganese/blood , Manganese/analysis , Trace Elements/blood , Testosterone/blood , Adult
5.
Environ Health Perspect ; 132(5): 57010, 2024 May.
Article En | MEDLINE | ID: mdl-38780454

BACKGROUND: Manganese (Mn) plays a significant role in both human health and global industries. Epidemiological studies of exposed populations demonstrate a dose-dependent association between Mn and neuromotor effects ranging from subclinical effects to a clinically defined syndrome. However, little is known about the relationship between early life Mn biomarkers and adolescent postural balance. OBJECTIVES: This study investigated the associations between childhood and adolescent Mn biomarkers and adolescent postural balance in participants from the longitudinal Marietta Communities Actively Researching Exposures Study (CARES) cohort. METHODS: Participants were recruited into CARES when they were 7-9 y old, and reenrolled at 13-18 years of age. At both time points, participants provided samples of blood, hair, and toenails that were analyzed for blood Mn and lead (Pb), serum cotinine, hair Mn, and toenail Mn. In adolescence, participants completed a postural balance assessment. Greater sway indicates postural instability (harmful effect), whereas lesser sway indicates postural stability (beneficial effect). Multivariable linear regression models were conducted to investigate the associations between childhood and adolescent Mn biomarkers and adolescent postural balance adjusted for age, sex, height-weight ratio, parent/caregiver intelligence quotient, socioeconomic status, blood Pb, and serum cotinine. RESULTS: CARES participants who completed the adolescent postural balance assessment (n=123) were 98% White and 54% female and had a mean age of 16 y (range: 13-18 y). In both childhood and adolescence, higher Mn biomarker concentrations were significantly associated with greater adolescent sway measures. Supplemental analyses revealed sex-specific associations; higher childhood Mn biomarker concentrations were significantly associated with greater sway in females compared with males. DISCUSSION: This study found childhood and adolescent Mn biomarkers were associated with subclinical neuromotor effects in adolescence. This study demonstrates postural balance as a sensitive measure to assess the association between Mn biomarkers and neuromotor function. https://doi.org/10.1289/EHP13381.


Biomarkers , Hair , Manganese , Nails , Postural Balance , Humans , Adolescent , Biomarkers/blood , Manganese/blood , Manganese/analysis , Female , Male , Child , Postural Balance/physiology , Hair/chemistry , Nails/chemistry , Cohort Studies , Environmental Exposure/statistics & numerical data , Lead/blood , Longitudinal Studies , Cotinine/blood , Environmental Pollutants/blood
6.
J Med Chem ; 67(10): 8261-8270, 2024 May 23.
Article En | MEDLINE | ID: mdl-38690886

This study aimed to develop a novel radiotracer using trastuzumab and the long-lived [52Mn]Mn isotope for HER2-targeted therapy selection and monitoring. A new Mn(II) chelator, BPPA, synthesized from a rigid bispyclen platform possessing a picolinate pendant arm, formed a stable and inert Mn(II) complex with favorable relaxation properties. BPPA was converted into a bifunctional chelator (BFC), conjugated to trastuzumab, and labeled with [52Mn]Mn isotope. In comparison to DOTA-GA-trastuzumab, the BPPA-trastuzumab conjugate exhibits a labeling efficiency with [52Mn]Mn approximately 2 orders of magnitude higher. In female CB17 SCID mice bearing 4T1 (HER2-) and MDA-MB-HER2+ (HER2+) xenografts, [52Mn]Mn-BPPA-trastuzumab demonstrated superior uptake in HER2+ cells on day 3, with a 3-4 fold difference observed on day 7. Overall, the hexadentate BPPA chelator proves to be exceptional in binding Mn(II). Upon coupling with trastuzumab as a BFC ligand, it becomes an excellent imaging probe for HER2-positive tumors. [52Mn]Mn-BPPA-trastuzumab enables an extended imaging time window and earlier detection of HER2-positive tumors with superior tumor-to-background contrast.


Manganese , Mice, SCID , Positron-Emission Tomography , Receptor, ErbB-2 , Trastuzumab , Animals , Female , Mice , Cell Line, Tumor , Chelating Agents/chemistry , Chelating Agents/chemical synthesis , Manganese/chemistry , Manganese/metabolism , Mice, Inbred BALB C , Picolinic Acids/chemistry , Positron-Emission Tomography/methods , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Receptor, ErbB-2/metabolism , Tissue Distribution , Trastuzumab/chemistry
7.
Front Endocrinol (Lausanne) ; 15: 1382844, 2024.
Article En | MEDLINE | ID: mdl-38689728

Equine metabolic syndrome (EMS) is a critical endocrine condition in horses, characterized by hyperinsulinemia, hyperlipidemia, and insulin resistance, posing a significant threat to their health. This study investigates the efficacy of supplementing EMS-affected horses with Arthrospira platensis enriched with Cr(III), Mg(II), and Mn(II) ions using biosorption process in improving insulin sensitivity and glucose tolerance, reducing inflammation, and mitigating obesity-related fat accumulation. Our results demonstrate that Arthrospira supplementation reduces baseline insulin and glucose levels, contributing to decreased adipose tissue inflammation. Furthermore, Arthrospira supplementation results in a decrease in body weight and improvements in overall body condition scores and cresty neck scores. Additionally, administration of Arthrospira leads to reduced levels of triglycerides and aspartate aminotransferase, indicating a decrease in hepatic adiposity and inflammation. These findings suggest that Arthrospira, enriched with essential micro- and macroelements, can be an advanced feed additive to enhance insulin sensitivity, promote weight reduction, and alleviate inflammatory processes, thereby improving the overall condition of horses affected by EMS. The use of Arthrospira as a feed additive has the potential to complement conventional management strategies for EMS.


Animal Feed , Chromium , Dietary Supplements , Horse Diseases , Inflammation , Insulin Resistance , Magnesium , Manganese , Metabolic Syndrome , Spirulina , Animals , Horses , Inflammation/metabolism , Metabolic Syndrome/veterinary , Metabolic Syndrome/metabolism , Horse Diseases/metabolism , Horse Diseases/prevention & control , Animal Feed/analysis , Magnesium/metabolism , Male , Female
8.
Sci Total Environ ; 932: 173045, 2024 Jul 01.
Article En | MEDLINE | ID: mdl-38734098

The main objective of this study was to develop and test a method of separating externally deposited Mn oxyhydroxides and co-precipitated elements from samples of aquatic moss (the moss Fontinalis antipyretica). The method, which uses 0.1 M hydroxylamine to dissolve the oxyhydroxides, was tested with samples collected in rivers with slightly acidic, well­oxygenated waters, where high rates of Mn precipitation occur. The method was effective (it extracted up to 84 % of the Mn) and selective (Fe oxyhydroxides were not extracted). The elements Ba, Cd, Zn and Ni were associated with the Mn oxyhydroxides, while Al, As, Cr, Cu, Fe, Hg and Pb were not. Deposition of Mn therefore increased the concentration of some elements in the moss samples. However, as Mn precipitation depends on Eh and pH, which are independent of the concentrations of the elements in water, the relationship between water and moss element concentrations is not clear (i.e. the data are noisy). This is a problem in biomonitoring studies, which assume a close relationship between element concentrations in moss and water. The value of the proposed extraction method is that it can be used to correct the effect of Mn deposition. We present an example of this correction applied to the Cd concentrations in the test data. We found that the noise introduced by the Mn, including age-related effects (observed by comparing concentrations in 0-2.5 and 2.2-5.0 cm sections from the shoot apex), can be reduced. Additionally, the correction revealed recent increases in Cd concentrations in one site that were not observed in the uncorrected data. Another finding of interest was the low content of total Mn and different extractability (of most elements) observed in moss samples collected in alkaline waters. Finally, we discuss how future studies designed for different environmental scenarios can benefit from application of the proposed method.


Bryophyta , Environmental Monitoring , Trace Elements , Water Pollutants, Chemical , Trace Elements/analysis , Water Pollutants, Chemical/analysis , Environmental Monitoring/methods , Bryophyta/chemistry , Manganese/analysis , Bryopsida/chemistry
9.
Langmuir ; 40(19): 10261-10269, 2024 May 14.
Article En | MEDLINE | ID: mdl-38693862

Carnosine is a natural bioactive dipeptide with important physiological functions widely used in food and medicine. Dipeptidase (PepD) from Serratia marcescens can catalyze the reverse hydrolytic reaction of ß-alanine with l-histidine to synthesize carnosine in the presence of Mn2+. However, it remains challenging to practice carnosine biosynthesis due to the low activity and high cost of the enzyme. Therefore, the development of biocatalysts with high activity and stability is of significance for carnosine synthesis. Here, we proposed to chelate Mn2+ to polyethylenimine (PEI) that induced rapid formation of calcium phosphate nanocrystals (CaP), and Mn-PEI@CaP was used for PepD immobilization via electrostatic interaction. Mn-PEI@CaP as the carrier enhanced the stability of the immobilized enzyme. Moreover, Mn2+ loaded in the carrier acted as an in situ activator of the immobilized PepD for facilitating the biocatalytic process of carnosine synthesis. The as-prepared immobilized enzyme (PepD-Mn-PEI@CaP) kept similar activity with free PepD plus Mn2+ (activity recovery, 102.5%), while exhibiting elevated thermal stability and pH tolerance. Moreover, it exhibited about two times faster carnosine synthesis than the free PepD system. PepD-Mn-PEI@CaP retained 86.8% of the original activity after eight cycles of batch catalysis without the addition of free Mn2+ ions during multiple cycles. This work provides a new strategy for the co-immobilization of PepD and Mn2+, which greatly improves the operability of the biocatalysis and demonstrates the potential of the immobilized PepD system for efficient carnosine synthesis.


Calcium Phosphates , Carnosine , Dipeptidases , Enzymes, Immobilized , Manganese , Nanoparticles , Polyethyleneimine , Carnosine/chemistry , Carnosine/metabolism , Polyethyleneimine/chemistry , Manganese/chemistry , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Calcium Phosphates/chemistry , Nanoparticles/chemistry , Dipeptidases/metabolism , Dipeptidases/chemistry , Serratia marcescens/enzymology , Biocatalysis
10.
Environ Sci Technol ; 58(19): 8576-8586, 2024 May 14.
Article En | MEDLINE | ID: mdl-38696240

Humic acid (HA) is ubiquitous in natural aquatic environments and effectively accelerates decontamination by permanganate (Mn(VII)). However, the detailed mechanism remains uncertain. Herein, the intrinsic mechanisms of HA's impact on phenolics oxidation by Mn(VII) and its intermediate manganese oxo-anions were systematically studied. Results suggested that HA facilitated the transfer of a single electron from Mn(VII), resulting in the sequential formation of Mn(VI) and Mn(V). The formed Mn(V) was further reduced to Mn(III) through a double electron transfer process by HA. Mn(III) was responsible for the HA-boosted oxidation as the active species attacking pollutants, while Mn(VI) and Mn(V) tended to act as intermediate species due to their own instability. In addition, HA could serve as a stabilizer to form a complex with produced Mn(III) and retard the disproportionation of Mn(III). Notably, manganese oxo-anions did not mineralize HA but essentially changed its composition. According to the results of Fourier-transform ion cyclotron resonance mass spectrometry and the second derivative analysis of Fourier-transform infrared spectroscopy, we found that manganese oxo-anions triggered the decomposition of C-H bonds on HA and subsequently produced oxygen-containing functional groups (i.e., C-O). This study might shed new light on the HA/manganese oxo-anion process.


Humic Substances , Manganese , Oxidation-Reduction , Phenols , Manganese/chemistry , Phenols/chemistry , Anions , Manganese Compounds/chemistry , Oxides/chemistry , Water Pollutants, Chemical/chemistry
11.
Bioconjug Chem ; 35(5): 703-714, 2024 May 15.
Article En | MEDLINE | ID: mdl-38708860

Manganese(II)-based contrast agents (MBCAs) are potential candidates for gadolinium-free enhanced magnetic resonance imaging (MRI). In this work, a rigid binuclear MBCA (Mn2-PhDTA2) with a zero-length linker was developed via facile synthetic routes, while the other dimer (Mn2-TPA-PhDTA2) with a longer rigid linker was also synthesized via more complex steps. Although the molecular weight of Mn2-PhDTA2 is lower than that of Mn2-TPA-PhDTA2, their T1 relaxivities are similar, being increased by over 71% compared to the mononuclear Mn-PhDTA. In the presence of serum albumin, the relaxivity of Mn2-PhDTA2 was slightly lower than that of Mn2-TPA-PhDTA2, possibly due to the lower affinity constant. The transmetalation reaction with copper(II) ions confirmed that Mn2-PhDTA2 has an ideal kinetic inertness with a dissociation half-life of approximately 10.4 h under physiological conditions. In the variable-temperature 17O NMR study, both Mn-PhDTA and Mn2-PhDTA2 demonstrated a similar estimated q close to 1, indicating the formation of monohydrated complexes with each manganese(II) ion. In addition, Mn2-PhDTA2 demonstrated a superior contrast enhancement to Mn-PhDTA in in vivo vascular and hepatic MRI and can be rapidly cleared through a dual hepatic and renal excretion pattern. The hepatic uptake mechanism of Mn2-PhDTA2 mediated by SLC39A14 was validated in cellular uptake studies.


Contrast Media , Liver , Magnetic Resonance Imaging , Manganese , Manganese/chemistry , Liver/diagnostic imaging , Liver/metabolism , Magnetic Resonance Imaging/methods , Animals , Contrast Media/chemistry , Contrast Media/chemical synthesis , Humans , Cation Transport Proteins/metabolism , Cation Transport Proteins/chemistry , Mice , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis
12.
Int J Mol Sci ; 25(9)2024 Apr 30.
Article En | MEDLINE | ID: mdl-38732149

Manganese (Mn), a cofactor for various enzyme classes, is an essential trace metal for all organisms. However, overexposure to Mn causes neurotoxicity. Here, we evaluated the effects of exposure to Mn chloride (MnCl2) on viability, morphology, synapse function (based on neurogranin expression) and behavior of zebrafish larvae. MnCl2 exposure from 2.5 h post fertilization led to reduced survival (60%) at 5 days post fertilization. Phenotypical changes affected body length, eye and olfactory organ size, and visual background adaptation. This was accompanied by a decrease in both the fluorescence intensity of neurogranin immunostaining and expression levels of the neurogranin-encoding genes nrgna and nrgnb, suggesting the presence of synaptic alterations. Furthermore, overexposure to MnCl2 resulted in larvae exhibiting postural defects, reduction in motor activity and impaired preference for light environments. Following the removal of MnCl2 from the fish water, zebrafish larvae recovered their pigmentation pattern and normalized their locomotor behavior, indicating that some aspects of Mn neurotoxicity are reversible. In summary, our results demonstrate that Mn overexposure leads to pronounced morphological alterations, changes in neurogranin expression and behavioral impairments in zebrafish larvae.


Behavior, Animal , Larva , Manganese , Neurogranin , Zebrafish , Animals , Zebrafish/metabolism , Larva/drug effects , Behavior, Animal/drug effects , Neurogranin/metabolism , Neurogranin/genetics , Manganese/toxicity , Chlorides/toxicity , Manganese Compounds
13.
Mar Genomics ; 75: 101107, 2024 Jun.
Article En | MEDLINE | ID: mdl-38735672

Previously studies have reported that MAGs (Metagenome-assembled genomes) belong to "Candidatus Manganitrophaceae" of phylum Nitrospirota with chemolithoautotrophic manganese oxidation potential exist in freshwater and hydrothermal environments. However, Nitrospirota members with chemolithoautotrophic manganese oxidation potential have not been reported in other marine environments. Through metagenomic sequencing, assembly and binning, nine metagenome-assembled genomes belonging to Nitrospirota are recovered from sediment of different depths in the polymetallic nodule area. Through the key functional genes annotation results, we find that these Nitrospirota have limited potential to oxidize organic carbon because of incomplete tricarboxylic acid cycle and most of them (6/9) have carbon dioxide fixation potential through different pathway (rTCA, WL or CBB). One MAG belongs to order Nitrospirales has the potential to use manganese oxidation to obtain energy for carbon fixation. In addition to manganese ions, the oxidation of inorganic nitrogen, sulfur, hydrogen and carbon monoxide may also provide energy for the growth of these Nitrospirota. In addition, different metal ion transport systems can help those Nitrospirota to resist heavy metal in sediment. Our work expands the understanding of the metabolic potential of Nitrospirota in sediment of polymetallic nodule region and may contributes to promoting the study of chemolithoautotrophic manganese oxidation.


Genome, Bacterial , Geologic Sediments , Metagenome , Geologic Sediments/microbiology , Pacific Ocean , Manganese/metabolism , Bacteria/genetics , Bacteria/classification
14.
Nat Commun ; 15(1): 3955, 2024 May 10.
Article En | MEDLINE | ID: mdl-38729929

Widespread manganese-sensing transcriptional riboswitches effect the dependable gene regulation needed for bacterial manganese homeostasis in changing environments. Riboswitches - like most structured RNAs - are believed to fold co-transcriptionally, subject to both ligand binding and transcription events; yet how these processes are orchestrated for robust regulation is poorly understood. Through a combination of single-molecule and bulk approaches, we discover how a single Mn2+ ion and the transcribing RNA polymerase (RNAP), paused immediately downstream by a DNA template sequence, are coordinated by the bridging switch helix P1.1 in the representative Lactococcus lactis riboswitch. This coordination achieves a heretofore-overlooked semi-docked global conformation of the nascent RNA, P1.1 base pair stabilization, transcription factor NusA ejection, and RNAP pause extension, thereby enforcing transcription readthrough. Our work demonstrates how a central, adaptable RNA helix functions analogous to a molecular fulcrum of a first-class lever system to integrate disparate signals for finely balanced gene expression control.


DNA-Directed RNA Polymerases , Gene Expression Regulation, Bacterial , Lactococcus lactis , Nucleic Acid Conformation , RNA, Bacterial , Riboswitch , Transcription, Genetic , Riboswitch/genetics , Lactococcus lactis/genetics , Lactococcus lactis/metabolism , DNA-Directed RNA Polymerases/metabolism , DNA-Directed RNA Polymerases/genetics , RNA, Bacterial/metabolism , RNA, Bacterial/genetics , RNA, Bacterial/chemistry , Manganese/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/chemistry , Single Molecule Imaging
15.
ACS Nano ; 18(20): 12830-12844, 2024 May 21.
Article En | MEDLINE | ID: mdl-38709246

The immunosuppressive microenvironment of cervical cancer significantly hampers the effectiveness of immunotherapy. Herein, PEGylated manganese-doped calcium sulfide nanoparticles (MCSP) were developed to effectively enhance the antitumor immune response of the cervical cancer through gas-amplified metalloimmunotherapy with dual activation of pyroptosis and STING pathway. The bioactive MCSP exhibited the ability to rapidly release Ca2+, Mn2+, and H2S in response to the tumor microenvironment. H2S disrupted the calcium buffer system of cancer cells by interfering with the oxidative phosphorylation pathway, leading to calcium overload-triggered pyroptosis. On the other hand, H2S-mediated mitochondrial dysfunction further promoted the release of mitochondrial DNA (mtDNA), enhancing the activation effect of Mn2+ on the cGAS-STING signaling axis and thereby activating immunosuppressed dendritic cells. The released H2S acted as an important synergist between Mn2+ and Ca2+ by modulating dual signaling mechanisms to bridge innate and adaptive immune responses. The combination of MCSP NPs and PD-1 immunotherapy achieved synergistic antitumor effects and effectively inhibited tumor growth. This study reveals the potential collaboration between H2S gas therapy and metalloimmunotherapy and provides an idea for the design of nanoimmunomodulators for rational regulation of the immunosuppressive tumor microenvironment.


Immunotherapy , Membrane Proteins , Pyroptosis , Tumor Microenvironment , Uterine Cervical Neoplasms , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Uterine Cervical Neoplasms/immunology , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/therapy , Female , Humans , Mice , Animals , Pyroptosis/drug effects , Membrane Proteins/metabolism , Manganese/chemistry , Manganese/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Nanoparticles/chemistry , Signal Transduction/drug effects , Cell Proliferation/drug effects , Calcium/metabolism , Mice, Inbred BALB C , Drug Screening Assays, Antitumor
16.
Environ Geochem Health ; 46(6): 203, 2024 May 02.
Article En | MEDLINE | ID: mdl-38695991

Manganese (Mn) is of particular concern in groundwater, as low-level chronic exposure to aqueous Mn concentrations in drinking water can result in a variety of health and neurodevelopmental effects. Much of the global population relies on drinking water sourced from karst aquifers. Thus, we seek to assess the relative risk of Mn contamination in karst by investigating the Shenandoah Valley, VA region, as it is underlain by both karst and non-karst aquifers and much of the population relies on water wells and spring water. Water and soil samples were collected throughout the Shenandoah Valley, to supplement pre-existing well water and spring data from the National Water Information System and the Virginia Household Water Quality Program, totaling 1815 wells and 119 springs. Soils were analyzed using X-ray fluorescence and Mn K-Edge X-ray absorption near-edge structure spectroscopy. Factors such as soil type, soil geochemistry, and aquifer lithology were linked with each location to determine if correlations exist with aqueous Mn concentrations. Analyzing the distribution of Mn in drinking water sources suggests that water wells and springs within karst aquifers are preferable with respect to chronic Mn exposure, with < 4.9% of wells and springs in dolostone and limestone aquifers exceeding 100 ppb Mn, while sandstone and shale aquifers have a heightened risk, with > 20% of wells exceeding 100 ppb Mn. The geochemistry of associated soils and spatial relationships to various hydrologic and geologic features indicates that water interactions with aquifer lithology and soils contribute to aqueous Mn concentrations. Relationships between aqueous Mn in spring waters and Mn in soils indicate that increasing aqueous Mn is correlated with decreasing soil Mn(IV). These results point to redox conditions exerting a dominant control on Mn in this region.


Groundwater , Manganese , Oxidation-Reduction , Soil , Water Pollutants, Chemical , Water Wells , Manganese/analysis , Groundwater/chemistry , Water Pollutants, Chemical/analysis , Soil/chemistry , Natural Springs/chemistry , Environmental Monitoring , Drinking Water/chemistry , Soil Pollutants/analysis , Soil Pollutants/chemistry , Spectrometry, X-Ray Emission , Environmental Exposure
17.
Artif Cells Nanomed Biotechnol ; 52(1): 321-333, 2024 Dec.
Article En | MEDLINE | ID: mdl-38795050

Polydopamine (PDA) stands as a versatile material explored in cancer nanomedicine for its unique properties, offering opportunities for multifunctional drug delivery platforms. This study explores the potential of utilizing a one-pot synthesis to concurrently integrate Fe, Gd and Mn ions into porous PDA-based theranostic drug delivery platforms called Ferritis, Gadolinis and Manganis, respectively. Our investigation spans the morphology, magnetic properties, photothermal characteristics and cytotoxicity profiles of those potent nanoformulations. The obtained structures showcase a spherical morphology, robust magnetic response and promising photothermal behaviour. All of the presented nanoparticles (NPs) display pronounced paramagnetism, revealing contrasting potential for MRI imaging. Relaxivity values, a key determinant of contrast efficacy, demonstrated competitive or superior performance compared to established, used contrasting agents. These nanoformulations also exhibited robust photothermal properties under near infra-red irradiation, showcasing their possible application for photothermal therapy of cancer. Our findings provide insights into the potential of metal-doped PDA NPs for cancer theranostics.


Indoles , Magnetic Resonance Imaging , Polymers , Indoles/chemistry , Humans , Polymers/chemistry , Contrast Media/chemistry , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Manganese/chemistry , Theranostic Nanomedicine/methods
18.
Int J Mol Sci ; 25(10)2024 May 13.
Article En | MEDLINE | ID: mdl-38791326

Chronic environmental exposure to toxic heavy metals, which often occurs as a mixture through occupational and industrial sources, has been implicated in various neurological disorders, including Parkinsonism. Vanadium pentoxide (V2O5) typically presents along with manganese (Mn), especially in welding rods and high-capacity batteries, including electric vehicle batteries; however, the neurotoxic effects of vanadium (V) and Mn co-exposure are largely unknown. In this study, we investigated the neurotoxic impact of MnCl2, V2O5, and MnCl2-V2O5 co-exposure in an animal model. C57BL/6 mice were intranasally administered either de-ionized water (vehicle), MnCl2 (252 µg) alone, V2O5 (182 µg) alone, or a mixture of MnCl2 (252 µg) and V2O5 (182 µg) three times a week for up to one month. Following exposure, we performed behavioral, neurochemical, and histological studies. Our results revealed dramatic decreases in olfactory bulb (OB) weight and levels of tyrosine hydroxylase, dopamine, and 3,4-dihydroxyphenylacetic acid in the treatment groups compared to the control group, with the Mn/V co-treatment group producing the most significant changes. Interestingly, increased levels of α-synuclein expression were observed in the substantia nigra (SN) of treated animals. Additionally, treatment groups exhibited locomotor deficits and olfactory dysfunction, with the co-treatment group producing the most severe deficits. The treatment groups exhibited increased levels of the oxidative stress marker 4-hydroxynonenal in the striatum and SN, as well as the upregulation of the pro-apoptotic protein PKCδ and accumulation of glomerular astroglia in the OB. The co-exposure of animals to Mn/V resulted in higher levels of these metals compared to other treatment groups. Taken together, our results suggest that co-exposure to Mn/V can adversely affect the olfactory and nigral systems. These results highlight the possible role of environmental metal mixtures in the etiology of Parkinsonism.


Manganese Compounds , Manganese , Mice, Inbred C57BL , Vanadium , Animals , Mice , Manganese/toxicity , Vanadium/toxicity , Male , Olfactory Bulb/metabolism , Olfactory Bulb/drug effects , Olfactory Bulb/pathology , Dopamine/metabolism , Vanadium Compounds , Oxidative Stress/drug effects , Parkinsonian Disorders/metabolism , Parkinsonian Disorders/chemically induced , alpha-Synuclein/metabolism , Chlorides/toxicity , Chlorides/metabolism , Tyrosine 3-Monooxygenase/metabolism , Aldehydes/metabolism , Substantia Nigra/metabolism , Substantia Nigra/drug effects , Substantia Nigra/pathology , Disease Models, Animal , 3,4-Dihydroxyphenylacetic Acid/metabolism
19.
Int J Mol Sci ; 25(10)2024 May 14.
Article En | MEDLINE | ID: mdl-38791379

Manganese (Mn) is a heavy metal that can cause excessive Mn poisoning in plants, disrupting microstructural homeostasis and impairing growth and development. However, the specific response mechanisms of leaves to Mn poisoning have not been fully elucidated. This study revealed that Mn poisoning of soybean plants resulted in yellowing of old leaves. Physiological assessments of these old leaves revealed significant increases in the antioxidant enzymes activities (peroxidase (POD), superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT)) and elevated levels of malondialdehyde (MDA), proline, indoleacetic acid (IAA), and salicylic acid (SA), under 100 µM Mn toxicity. Conversely, the levels of abscisic acid (ABA), gibberellin 3 (GA3), and jasmonic acid (JA) significantly decreased. The Mn content in the affected leaves significantly increased, while the levels of Ca, Na, K, and Cu decreased. Transcriptome analysis revealed 2258 differentially expressed genes in the Mn-stressed leaves, 744 of which were upregulated and 1514 were downregulated; these genes included genes associated with ion transporters, hormone synthesis, and various enzymes. Quantitative RT-PCR (qRT-PCR) verification of fifteen genes confirmed altered gene expression in the Mn-stressed leaves. These findings suggest a complex gene regulatory mechanism under Mn toxicity and stress, providing a foundation for further exploration of Mn tolerance-related gene regulatory mechanisms in soybean leaves. Using the methods described above, this study will investigate the molecular mechanism of old soybean leaves' response to Mn poisoning, identify key genes that play regulatory roles in Mn toxicity stress, and lay the groundwork for cultivating high-quality soybean varieties with Mn toxicity tolerance traits.


Gene Expression Regulation, Plant , Glycine max , Manganese , Plant Leaves , Glycine max/drug effects , Glycine max/metabolism , Glycine max/genetics , Plant Leaves/drug effects , Plant Leaves/metabolism , Manganese/toxicity , Manganese/metabolism , Gene Expression Regulation, Plant/drug effects , Stress, Physiological/drug effects , Antioxidants/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Superoxide Dismutase/metabolism , Superoxide Dismutase/genetics , Malondialdehyde/metabolism , Gene Expression Profiling
20.
Bioresour Technol ; 402: 130794, 2024 Jun.
Article En | MEDLINE | ID: mdl-38703966

Carbon deficits in inflow frequently lead to inefficient nitrogen removal in constructed wetlands (CWs) treating tailwater. Solid carbon sources, commonly employed to enhance denitrification in CWs, increase carbon emissions. In this study, MnO2 was incorporated into polycaprolactone substrates within CWs, significantly enhancing NH4+-N and NO3--N removal efficiencies by 48.26-59.78 % and 96.84-137.23 %, respectively. These improvements were attributed to enriched nitrogen-removal-related enzymes and increased plant absorption. Under high nitrogen loads (9.55 ± 0.34 g/m3/d), emissions of greenhouse gases (CO2, CH4, and N2O) decreased by 147.23-202.51 %, 14.53-86.76 %, and 63.36-87.36 %, respectively. N2O emissions were reduced through bolstered microbial nitrogen removal pathways by polycaprolactone and MnO2. CH4 accumulation was mitigated by the increased methanotrophs and dampened methanogenesis, modulated by manganese. Additionally, manganese-induced increases in photosynthetic pigment contents (21.28-64.65 %) fostered CO2 sequestration through plant photosynthesis. This research provides innovative perspectives on enhancing nitrogen removal and reducing greenhouse gas emissions in constructed wetlands with polymeric substrates.


Carbon , Methane , Nitrogen , Wetlands , Nitrogen/metabolism , Carbon/metabolism , Methane/metabolism , Polyesters/metabolism , Polyesters/chemistry , Manganese/pharmacology , Plants/metabolism , Denitrification , Nitrous Oxide/metabolism , Carbon Dioxide/metabolism , Biodegradation, Environmental , Photosynthesis
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