Secondary Mn Research Articles

Diagnosis and treatment of secondary nephrotic syndrome with rash as the first symptom: a case report

BackgroundMembranous nephropathy (MN) is a common type of nephrotic syndrome (NS) in adults, accounting for about 20–30% of cases. Although secondary to specific factors, the coexistence of MN and mantle cell lymphoma (MCL) has been scarcely reported in clinical literature.Case presentationA 59-year-old Chinese male was admitted to the hospital with a generalized pruritic rash with bilateral lower extremity edema, which did not improve significantly after symptomatic treatment. He had undergone renal biopsy, and the diagnosis was thought to be secondary MN (SMN), therefore, we did a lymph node biopsy on the patient and found that MN was complicated with MCL. Soon after, the patient was admitted to the hematology department for a BR chemotherapy regimen (composed of bendamustine 90 mg/m2 BSA (body surface area), rituximab 375 mg/m2 BSA and dexamethasone 5 mg), and during the post-treatment follow-up, both his symptoms and renal function improved.ConclusionsThe mechanism underlying the combination of SMN and MCL remains elusive and exceedingly rare, consequently often overlooked in clinical practice. This case serves to offer valuable clinical insights for diagnosis and treatment, while emphasizing the pivotal role of renal pathology in clinical assessment.

Mannose-Binding Lectin Deposition in Membranous Nephropathy and Differentiation of Primary from Secondary Forms.

We investigated the lack of mannose-binding lectin (MBL) deposition in patients with secondary MNs (sMNs) with the presence of IgG4 deposition in relation to the presence of MBL deposition in patients with primary MNs (pMNs). We also established a connection between the stage of MN and MBL deposition. Materials from 72 renal biopsies with proven MN were used for immunohistochemistry staining (IHC) for the phospholipase A2 receptor (PLA2R), immunoglobulin subtype IgG4, and MBL. Patients were separated into one of the following three groups: primary MN (pMN), idiopathic MN (iMN), and secondary MN (sMN). Serum antibodies for PLA2R and thrombospondin type-I-domain-containing 7A (THSD7A) were also used for the precise evaluation of the type of MN, as well as for detecting positivity for PLA2R using IHC. Which stage of MN was present in relation to the deposition of MBL was evaluated. In total, 50 patients were positive for IgG4, 34 with pMN, 12 with iMN, and 4 with sMN. A total of 20 patients were positive for MBL, 14 with pMN and 6 with iMN; no MBL deposits were found in patients with sMN. MBL positivity was predominantly present in the first two stages of MN, with a gradual reduction in the later stages. The activation of the lectin-complement pathway occurs in the early stages of the disease and is associated with the deposition of IgG4; IgG4 deposition is present in sMN, but there is no MBL deposition. IgG4 cannot be used for the differentiation of primary from secondary MNs, but the lack of MBL can be used as a marker for sMN in the early stages of the disease.

Obinutuzumab in Refractory Membranous Nephropathy: A Case Series

Rationale & ObjectiveMembranous nephropathy (MN), recognized as an autoimmune kidney disease, responds well to anti-CD20 monoclonal antibodies. Obinutuzumab, a type Ⅱ humanized anti-CD20 and immunoglobulin G1 Fc-optimized monoclonal antibody, compared to rituximab, has demonstrated superior efficacy in B cell leukemia and lymphoma, especially in rituximab-resistant cases. However, the efficacy and safety of obinutuzumab in MN remain unclear. Study DesignRetrospective cohort study. Setting & ParticipantsA total of 18 patients who were diagnosed as MN and received obinutuzumab at our center, without secondary MN, undergoing dialysis, history of kidney transplantation, or infections requiring treatment. ExposureObinutuzumab treatment. OutcomesPrimary outcomes included remission rate, time to first remission, and first relapse-free survival time during the follow-up period. Analytical ApproachSurvival analysis was conducted with Cox proportional hazards models, Log-rank test, and Kaplan–Meier survival analysis. ResultsMN patients (median age 52.5 years, 83% males) received an average dose of 2.1 ± 0.8 g obinutuzumab during a median follow-up period of 13.6 months. During follow-up, 17 patients (94.4%) achieved remission, with 12 patients (66.7%) achieving partial remission (PR) and 5 patients (27.8%) achieving complete remission (CR). The median time to first remission and first relapse-free survival time was 2.7 (1.0, 6.1) months and 9.8 (2.6, 11.2) months, respectively. Of 12 patients with previous rituximab treatment, all achieved remission successfully, with 8 (66.7%) achieving PR and 4 (33.3%) achieving CR. Adverse events were mostly mild, and no severe treatment-related adverse events were observed. LimitationsLimited or missing data, risks of selection bias, or recall bias; underestimated first relapse-free survival time due to limited follow-up period; unmonitored counts of CD19+ B cells and other lymphocyte subsets. ConclusionsObinutuzumab demonstrated promising efficacy and safety in inducing remission in MN, particularly in patients with an unsatisfactory response to rituximab.

Evidence for and against manganese deficiency as causal for congenital joint deficiency disease or death in fetal and neonatal cattle.

Measures of manganese (Mn) status in cattle vary among studies, and no single criterion accurately predicts or diagnoses Mn deficiency and pathologic outcomes. Mn deficiency causes congenital joint laxity and dwarfism (CJLD) when total dietary intake is <20 ppm Mn dry matter (DM) for most of the pregnancy. However, the recommended dietary intake of 40 ppm DM can also result in clinical Mn deficiency. Some studies have found that CJLD occurs in calves from cows fed red clover or silage but not in calves from cows fed hay. The concentration of Mn in the liver is the best indicator of Mn status in neonates and adults but cannot be interpreted in fetuses. Serum, plasma, and whole blood concentrations of Mn are unreliable indicators of bovine Mn status. The primary objective of our report is to present evidence linking CJLD to a primary or secondary Mn deficiency. To predict and diagnose Mn deficiency in cattle, we propose using a combination of clinical signs, dietary Mn, liver Mn at birth and beyond, positive response to Mn supplementation or the replacement of silage with other forages, and ruling out other causes of malformations. By following these recommendations, we expect that CJLD and gestational death will decrease as hepatic Mn concentrations increase at birth. Many publications we reviewed are not statistically sound, and future research should include a statistician from the initial discussions of the study through the final publication.

Boundary‐Rich Carbon‐Based Electrocatalysts with Manganese(II)‐Coordinated Active Environment for Selective Synthesis of Hydrogen Peroxide

AbstractCoordinated manganese (Mn) electrocatalysts owing to their electronic structure flexibility, non‐toxic and earth abundant features are promising for electrocatalytic reactions. However, achieving selective hydrogen peroxide (H2O2) production through two electron oxygen reduction (2e‐ORR) is a challenge on Mn‐centered catalysts. Targeting this goal, we report on the creation of a secondary Mn(II)‐coordinated active environment with reactant enrichment effect on boundary‐rich porous carbon‐based electrocatalysts, which facilitates the selective and rapid synthesis of H2O2 through 2e‐ORR. The catalysts exhibit nearly 100 % Faradaic efficiency and H2O2 productivity up to 15.1 mol gcat−1 h−1 at 0.1 V versus reversible hydrogen electrode, representing the record high activity for Mn‐based electrocatalyst in H2O2 electrosynthesis. Mechanistic studies reveal that the epoxide and hydroxyl groups surrounding Mn(II) centers improve spin state by modifying electronic properties and charge transfer, thus tailoring the adsorption strength of *OOH intermediate. Multiscale simulations reveal that the high‐curvature boundaries facilitate oxygen (O2) adsorption and result in local O2 enrichment due to the enhanced interaction between carbon surface and O2. These merits together ensure the efficient formation of H2O2 with high local concentration, which can directly boost the tandem reaction of hydrolysis of benzonitrile to benzamide with nearly 100 % conversion rate and exclusive benzamide selectivity.

Investigating the Use of Mg-3Pb Alloy for Cathodic Protection of Mg Alloys

Magnesium alloys possess many interesting properties, including high strength-to-weight ratios, good castability, and excellent biocompatibility. However, its use has been limited because they are also highly reactive and susceptible to corrosion in aqueous environments. As a result, the development of effective corrosion protection strategies for Mg alloys represents a significant challenge for many industrial applications, particularly in the aerospace, automotive, and biomedical industries.Sacrificial cathodic protection is a commonly used strategy to enhance the durability of metallic materials. This method involves the use of an active metal (known as the sacrificial anode) in galvanic contact with the metal to be protected from corrosion, which acts as the cathode. Due to their low corrosion potential, Mg alloys have traditionally served as sacrificial anodes to protect more noble metals such as steel, aluminum, and zinc. However, the growing interest in Mg alloys for industrial applications has led to the development of effective corrosion protection alternatives for Mg alloy components. Among them, the use of Mg alloy coatings as the anode material for the sacrificial protection of other Mg alloys is an interesting strategy. This approach offers several advantages such as minimized galvanic corrosion due to their comparable electrochemical behavior, as well as enhanced adhesion between the anode and the substrate.One of the key requirements for a metallic material to be used as a sacrificial anode is that its electrode potential must be more negative than that of the metal being protected. Additionally, the anode material must be chemically stable in the environment in which it will be located. These conditions are largely dependent on the composition of the anode material. Although recent studies have aimed to enhance the cathodic protection properties of Mg alloys for their use in industrial applications, such work remains restricted. This is due to the limited number of alloying elements with lower standard reduction potentials than Mg that are stable in solution, thereby decreasing the anode corrosion potential. In addition, Mg exhibits enhanced hydrogen evolution rates with increasing anodic polarization, which contradicts expectations of standard electrochemical kinetics and leads to significantly increased rates of self-dissolution. This phenomenon is termed anomalous hydrogen evolution (HE).This work investigates the potential of Mg-3Pb alloy as possible sacrificial anode material for the corrosion protection of three industrially important Mg alloys: AZ31, AM60, and AZ91. For that purpose, a Mg-3Pb alloy was casted in-house and its microstructural characteristics and electrochemical behavior were studied. Furthermore, galvanic corrosion between the Mg-3Pb alloy and the industrially relevant Mg alloys, AZ31, AM60, and AZ91, was evaluated in 0.1 M NaCl solution. The choice of Pb as an alloying element was motivated by its extremely low exchange current density for the HE reaction (i0,H2,Pb) on the order of 10-12 A/cm2. This was expected to result in reduced HE rates under cathodic polarization, which shifts the corrosion potential (Ecorr) to more negative values, and during anodic polarization, hindering anomalous HE and reducing self-dissolution.The microstructural characterization of the Mg-3Pb alloy revealed that it consisted of large α-Mg grains with the presence of a small amount of secondary phases, including Al, Si, Mn, Fe-containing intermetallics and oxide particles. Additionally, scanning electron microscopy revealed the occurrence of remarkable Pb segregation at grain boundaries.Electrochemical measurements showed that the Ecorr associated with the Mg-3Pb alloy was consistently lower than those of the AZ31, AM60, and AZ91 alloys during 24 hours of immersion in the test solution. Moreover, potentiodynamic polarization confirmed that the Mg-3Pb alloy exhibited the lowest cathodic kinetics. In terms of anomalous HE, which is directly related to the self-dissolution rate of the Mg alloy anode material, galvanostatic polarization at different anodic current densities showed that the HE current densities were linear with respect to the applied current density. Additionally, the charge associated with the HE was in the range of 40–50% of the applied anodic charge, which is consistent with previous findings for high purity Mg.Finally, ZRA measurements indicated that the galvanic current of the Mg-3Pb alloy remained anodic for 24 hours of immersion with no polarity reversal, indicating that the Pb-containing alloy served as sacrificial anode for the AZ31, AM60, and AZ91 alloys.In conclusion, the use of Mg-3Pb alloy in cathodic protection systems for Mg alloys has proved to be a viable option in 0.1 M NaCl solution, offering new possibilities for its use in various applications.Funding: This work was supported by the State Research Agency (MICINN), the Spanish National Research Council (CSIC) and European Regional Development Fund (ERDF) under the project RYC2019-027006-I (AEI/FEDER/UE).

Material flow analysis on the critical resources from spent power lithium-ion batteries under the framework of China's recycling policies

With the rapid growth of electric vehicles in China, the number of spent power lithium-ion batteries is dramatically increased. Considering the environmental risk, security risk, and potential resource value, China has issued a series of laws and regulations to manage the spent power lithium-ion batteries. This work employs the material flow analysis method to evaluate the material flows of Li, Ni, Co, and Mn during the life cycle of power lithium-ion batteries under the framework of China's recycling policy system. The results show that the demand for primary Li, Ni, Co, and Mn can achieve 26.9, 68.1, 20.4, and 21.9 kt in 2021, and a lot of primary critical resources will inburst the in-use stage. Moreover, the number of secondary Li, Ni, Co, and Mn can achieve 6.1, 15.4, 4.6, and 5 kt in 2021, accounting for 22.7%, 22.6%, 22.5%, and 22.8% of their corresponding demand. Based on the economic evaluation under the framework of China's recycling policy system, it is found that the potential recycling values of Li, Ni, Co, and Mn are approximately 966, 523, 414, and 43 million RMB yuan, which are 66.4%, 71%, 59.6%, and 66.4% higher than those in the absence of China's recycling policy system. It is implied that China's recycling policy system could markedly improve the collection rate by reducing losses and indirectly enhancing the recycling and reuse of spent power lithium-ion batteries. This work is expected to provide guidance for policymakers to improve the management of spent power lithium-ion batteries in China.

Measurement of urinary exosomal phospholipase A2 receptor is a sensitive method for diagnosis of PLA2R-associated membranous nephropathy.

The discovery of phospholipase A2 receptor (PLA2R) and its antibody (aPLA2Rab) has paved the way for diagnosing PLA2R-associated membranous nephropathy (PLA2R-MN) with a high specificity of 98%. However, the sensitivity was only 40% to 83.9%, and there is ongoing discussion around determining the optimal threshold for diagnosis. Recent advancements in the use of exosomes, a novel form of "liquid biopsy," have shown great promise in identifying markers for various medical conditions. Protein mass spectrometry and western blot were applied to verify the existence of PLA2R antigen in the urine exosome. We then evaluated the efficacy of urinary exosomal PLA2R antigen alone or combined with serum aPLA2Rab level to diagnose PLA2R-MN. The urinary exosomes contained a high abundance of PLA2R antigen as evidenced by protein mass spectrometry and western blot in 85 PLA2R-MN patients vs the disease controls (14 secondary MN patients, 22 non-MN patients and 4 PLA2R-negative MN patients) and 20 healthy controls. Of note, urinary exosomal PLA2R antigen abundance also had a good consistency with the PLA2R antigen level in the renal specimens of PLA2R-MN patients. The sensitivity of urinary exosomal PLA2R for diagnosing PLA2R-MN reached 95.4%, whereas the specificity was 63.3%. Combining detection of the urinary exosomal PLA2R and serum aPLA2Rab could develop a more sensitive diagnostic method for PLA2R-MN, especially for patients with serum aPLA2Rab ranging from 2 to 20 RU/mL. Measurement of urinary exosomal PLA2R could be a sensitive method for the diagnosis of PLA2R-MN.

#6502 ETIOLOGICAL SPECTRUM OF MEMBRANOUS NEPHROPATHY

Abstract Background and Aims Primary MN includes forms of MN in which there is a humoral autoimmune response to a normal podocyte antigen in the absence of secondary features or etiologies of disease. Antigens implicated in primary MN include PLA2R, thrombospondin type-1 domain-containing 7A (THSD7A), neural epidermal growth factor-like 1 (NELL1), semaphorin 3B (Sema3B), the serine protease high-temperature requirement A1 (HTRA1), protocadherin 7 (PCDH7), and others. PLA2R associated MN is most common MN among primary MN. Nowadays, a significant number of newer antigens implicating MN are being discovered. Research is ongoing for a better understanding of the role of these antigens in pathophysiology, and targeted therapeutic implications in future if possible. We aim to analyze the etiological spectrum associated with different antigens in patients with Membranous Nephropathy. We assessed the renal tissue staining of autoantigens PLA2R, THSD7A, and NELL-1 in patients with biopsy-proven Membranous Nephropathy. Method This was a single center ambispective observational study. The study was performed up till September 2022 for prospective data, and retrospective data from January 2018 to March 2021 was retrieved from the medical records department of the institute. The study included patients with biopsy-proven Membranous Nephropathy (Primary and secondary). The primary outcome was to study the etiological spectrum of Membranous Nephropathy. Results A total of 90 patients were included in the study of membranous nephropathy over the period of 4 years. 72 cases had primary MN whereas 18 cases had secondary MN. The mean age was 42.01 ± 14.6 years. Among 18 cases of Secondary MN, the majority of the cases were of lupus nephritis 14 (78%), while other etiologies of secondary MN were malignancy related (11%), rheumatoid arthritis (5.5%) and HCV (5.5%). PLA2R renal tissue positivity was found in 44 (61.1%) cases of primary MN, whereas in 4 (22.2%) cases of Secondary MN. The THSD7A was found in 4 (5.6%) cases of primary MN. One patient of MN was dual PLA2R and NELL1 positive. Two cases of MN were dual PLA2R and THSD7A positive. Renal tissue staining for NELL-1 was found in 8 (11.1%) cases of primary MN whereas it was found in 1 (5.6%) case of secondary MN. In terms of clinical presentation, proteinuria is the most common clinical finding present in nearly all the patients (80%). Most of the cases with nephrotic syndrome (60%) belonged to primary MN. Conclusion PLA2R is the most common etiology of Primary membranous nephropathy. None of the antigens was exclusive to primary membranous nephropathy.

Microglial immune regulation by epigenetic reprogramming through histone H3K27 acetylation in neuroinflammation.

Epigenetic reprogramming is the ability of innate immune cells to form memories of environmental stimuli (priming), allowing for heightened responses to secondary stressors. Herein, we explored microglial epigenetic marks using the known inflammagen LPS as a memory priming trigger and Parkinsonian-linked environmental neurotoxic stressor manganese (Mn) as the secondary environmental trigger. To mimic physiological responses, the memory priming trigger LPS treatment was removed by triple-washing to allow the cells' acute inflammatory response to reset back before applying the secondary insult. Our results show that after the secondary Mn insult, levels of key proinflammatory markers, including nitrite release, iNOS mRNA and protein expression, Il-6, Il-α and cytokines were exaggerated in LPS-primed microglia. Our paradigm implies primed microglia retain immune memory that can be reprogrammed to augment inflammatory response by secondary environmental stress. To ascertain the molecular underpinning of this neuroimmune memory, we further hypothesize that epigenetic reprogramming contributes to the retention of a heightened immune response. Interestingly, Mn-exposed, LPS-primed microglia showed enhanced deposition of H3K27ac and H3K4me3 along with H3K4me1. We further confirmed the results using a PD mouse model (MitoPark) and postmortem human PD brains, thereby adding clinical relevance to our findings. Co-treatment with the p300/H3K27ac inhibitor GNE-049 reduced p300 expression and H3K27ac deposition, decreased iNOS, and increased ARG1 and IRF4 levels. Lastly, since mitochondrial stress is a driver of environmentally linked Parkinson's disease (PD) progression, we examined the effects of GNE-049 on primary trigger-induced mitochondrial stress. GNE-049 reduced mitochondrial superoxide, mitochondrial circularity and stress, and mitochondrial membrane depolarization, suggesting beneficial consequences of GNE-049 on mitochondrial function. Collectively, our findings demonstrate that proinflammatory primary triggers can shape microglial memory via the epigenetic mark H3K27ac and that inhibiting H3K27ac deposition can prevent primary trigger immune memory formation and attenuate subsequent secondary inflammatory responses.

Structural and Raman studies of MnO2 and Mn2O3 nano-particles

In this work MnO 2 with secondary phases Mn 2 O 3 nano-particles were synthesized by using sol- gel route method. This method was carried out under the thermal treatment at 500 °C for 2 h. Structural parameters were extracted by X-ray Diffractometer (XRD). The phase and crystallite size of MnO 2 and secondary phase Mn 2 O 3 were figured out by XRD. The peaks from XRD show different crystalline sizes are ∼59 nm, 51 nm, 53 nm, 63 nm, and 65 nm. The average crystallite size is 58 nm. The Raman studies of the sample were also carried out. The vibrational studies through Raman Spectroscopy technique gives peak at 509 cm −1 shows MnO 2 .

Primary membranous nephropathy: an endless story.

Primary membranous nephropathy (PMN) is an autoimmune disease caused by the attack of autoantibodies against podocyte antigens leading to the in situ production of immune complexes. However, the etiology is unknown and the pathogenesis is still far from being completely elucidated. MN is prevalently idiopathic or primary, but in about 20-30% of cases it is secondary to chronic infections, systemic diseases, exposure to drugs, or malignancy. The differentiation between primary and secondary MN may be difficult, particularly when MN precedes signs and symptoms of the original disease, as in some cases of cancer or systemic lupus erythematosus. The natural course of PMN is variable, but in the long term 40-60% of patients with nephrotic syndrome progress to end-stage renal disease (ESRD) or die from thrombotic or cardiovascular events. PMN is a treatable disease. Patients with asymptomatic proteinuria should receive supportive care. Immunosuppressive treatments should be given to patients with nephrotic syndrome or risk of progression. The most frequently adopted treatments rely on cyclical therapy alternating steroids with a cytotoxic agent every other month, i.e., rituximab at different doses, or calcineurin inhibitors plus low-dose steroids. A good rate of response may be obtained but relapses can occur. Randomized controlled trials, with adequate size, long-term follow-up, and fair definition of endpoints are needed to identify treatment with the best therapeutic index.

Enhanced Magnetocaloric Properties of Annealed Melt-Extracted Mn1.3Fe0.6P0.5Si0.5 Microwires

The highly regarded Fe2P-based magnetocaloric materials are usually fabricated by ball milling, and require an additional extended annealing treatment at high temperatures (at temperatures up to 1423 K for several hours to days). In this work, we show that fabricating Mn1.3Fe0.6P0.5Si0.5 into the form of microwires attained 82.1 wt.% of the desired Fe2P phase in the as-cast state. The microwires show a variable solidification structure along the radial direction; close to the copper wheel contact, Fe2P phase is in fine grains, followed by dendritic Fe2P grains and finally secondary (Mn,Fe)5Si3 phase in addition to the dendritic Fe2P grains. The as-cast microwires undergo a ferro- to para-magnetic transition with a Curie temperature of 138 K, showing a maximum isothermal magnetic entropy change of 4.6 J kg−1 K−1 for a magnetic field change of 5 T. With further annealing, a two-fold increase in the maximum isothermal magnetic entropy change is found in the annealed microwires, which reveal 88.1 wt.% of Fe2P phase.

Groundwater input drives large variance in soil manganese concentration and reactivity in a forested headwater catchment

AbstractIn headwater catchments, surface groundwater discharge areas have unique soil biogeochemistry and can be hot spots for solute contribution to streams. Across the northeastern United States, headwater hillslopes with surface groundwater discharge were enriched in soil Mn, including Watershed 3 of Hubbard Brook Experimental Forest, New Hampshire. Soils of this site were investigated along a grid to determine extent of Mn‐rich zone(s) and relationships to explanatory variables using ordinary kriging. The O and B horizons were analyzed for total secondary Mn and Fe, Cr oxidation potential, total organic C, moisture content, wetness ratio, and pH. Two Mn hot spots were found: a poorly drained, flowing spring (Location A); and a moderately well‐drained swale (Location B). Both had ∼6,000–9,000 mg Mn kg–1 soil. However, Location A had high Cr oxidation potential (a measure of Mn reactivity), whereas Location B did not. Location C, a poorly drained seep with slow‐moving water, had lower Mn content and Cr oxidation potential. Manganese‐rich soil particles were analyzed using X‐ray absorption near‐edge structure and micro‐X‐ray diffraction; the dominant oxidation state was Mn(IV), and the dominant Mn oxide species was a layer‐type Mn oxide (L‐MnO2). We propose input of Mn(II) with groundwater, which is oxidized by soil microbes. Studies of catchment structure and response could benefit from identifying hot spots of trace metals, sourced mainly from parent material but which accumulate according to hydropedologic conditions. Small‐scale variation in Mn enrichment due to groundwater and microtopography appears to be more important than regional‐scale variation due to air pollution.

Anti-phospholipase A2 Receptor Antibody in Differentiation and Prognostication of Membranous Nephropathy.

Anti-M-type phospholipase A2 receptor (anti-PLA2R) antibody is believed to be associated with primary membranous nephropathy (pMN) and absent in secondary MN (sMN). There are few data regarding utility of anti-PLA2R antibody as a prognosticator. Our study aimed to compare the incidence of positive serum anti-PLA2R antibody titer in pMN versus sMN and correlation with clinical outcome. From August 2015 to July 2019, patients with biopsy-proven MN were evaluated for serum anti-PLA2R antibody titers by the enzyme-linked immunosorbent assay. The subset of cases was repeated to monitor the clinical response in terms of 24 h proteinuria. A total of 169 patients, 65 pMN and 104 sMN were studied. Anti-PLA2R antibody was found in 41 (63.08%) pMN with mean titer, 232.62 RU/mL, and 40 (38.46%) sMN with mean titer 253.59 RU/mL. Out of positive antiPLA2R antibody titer in pMN cases, 15 were retested twice to 5 times with mean titers of 78.95, 36.27, 13.9, and 15.45 RU/mL, respectively. Out of positive anti-PLA2R antibody in sMN cases, 11 were retested twice to five times with mean titers of 104.42, 122.49, 12.33, and 17.2 RU/mL, respectively. All patients with decreasing anti-PLA2R antibody titer in both groups had clinical remission, with a decrease in mean 24 h proteinuria from 7.11 g to 3.36 g in pMN and 5.97 g to 3.41 g in sMN. Ten pMN and 11 sMN patients without remission showed persistent positive anti- PLA2R antibody titer. Anti-PLA2R antibody titer may be elevated in pMN/sMN. It can also be used as a noninvasive prognostic marker for MN.

Root-to-shoot iron partitioning in Arabidopsis requires IRON-REGULATED TRANSPORTER1 (IRT1) protein but not its iron(II) transport function.

IRON-REGULATED TRANSPORTER1 (IRT1) is the root high-affinity ferrous iron (Fe) uptake system and indispensable for the completion of the life cycle of Arabidopsis thaliana without vigorous Fe supplementation. Here we provide evidence supporting a second role of IRT1 in root-to-shoot partitioning of Fe. We show that irt1 mutants overaccumulate Fe in roots, most prominently in the cortex of the differentiation zone in irt1-2, compared to the wild type. Shoots of irt1-2 are severely Fe-deficient according to Fe content and marker transcripts, as expected. We generated irt1-2 lines producing IRT1 mutant variants carrying single amino-acid substitutions of key residues in transmembrane helices IV and V, Ser206 and His232, which are required for transport activity in yeast. Root short-term 55 Fe uptake rates were uninformative concerning IRT1-mediated transport. Overall irt1-like concentrations of the secondary substrate Mn suggested that the transgenic Arabidopsis lines also remain incapable of IRT1-mediated root Fe uptake. Yet, IRT1S206A partially complements rosette dwarfing and leaf chlorosis of irt1-2, as well as root-to-shoot Fe partitioning and gene expression defects of irt1-2, all of which are fully complemented by wild-type IRT1. Taken together, these results suggest a regulatory function for IRT1 in root-to-shoot Fe partitioning that does not require Fe transport activity of IRT1. Among the genes of which transcript levels are partially dependent on IRT1, we identify MYB DOMAIN PROTEIN10, MYB DOMAIN PROTEIN72 and NICOTIANAMINE SYNTHASE4 as candidates for effecting IRT1-dependent Fe mobilization in roots. Understanding the biological functions of IRT1 will help to improve Fe nutrition and the nutritional quality of agricultural crops.

Manganese-Oxidizing Antarctic Bacteria (Mn-Oxb) Release Reactive Oxygen Species (ROS) as Secondary Mn(II) Oxidation Mechanisms to Avoid Toxicity.

Simple SummaryManganese (Mn)-oxidizing bacteria (MnOxb) are an essential group of microorganisms that oxidize soluble Mn(II) to form precipitate Mn(III) minerals, playing a crucial role in soil formation. The Fildes Peninsula is one of the fastest-warming areas globally and, therefore, the maritime Antarctic soils from this pivotal location allow for the examination of the effect of temperature on bacterial communities. The temperature causes an increase in the microbial respiratory rate, producing reactive oxygen species (ROS), which are harmful to bacteria. We evaluate an evasive secondary non-enzymatic mechanism for ROS production under increasing temperature in MnOxb isolated from Antarctic soils. Bacteria produce ROS capable of oxidizing Mn(II) as temperature increases, contributing to the enzymatic pathway protecting microbial cells from Mn(II) toxicity. In addition, we determine that certain strains, such as Arthobacter oxydans, can use these ROS as mechanisms to protect themselves from Mn toxicity at high concentrations. In conclusion, we describe a secondary mechanism of Mn(II) oxidation in bacterial strains of Antarctic soils.Manganese (Mn) oxidation is performed through oxidative Mn-oxidizing bacteria (MnOxb) as the main bio-weathering mechanism for Mn(III/IV) deposits during soil formation. However, with an increase in temperature, the respiration rate also increases, producing Reactive Oxygen Species (ROS) as by-products, which are harmful to microbial cells. We hypothesize that bacterial ROS oxidize Mn(II) to Mn(III/IV) as a secondary non-enzymatic temperature-dependent mechanism for cell protection. Fourteen MnOxb were isolated from Antarctic soils under the global warming effect, and peroxidase (PO) activity, ROS, and Mn(III/IV) production were evaluated for 120 h of incubation at 4 °C, 15 °C, and 30 °C. ROS contributions to Mn oxidation were evaluated in Arthrobacter oxydans under antioxidant (Trolox) and ROS-stimulated (menadione) conditions. The Mn(III/IV) concentration increased with temperature and positively correlated with ROS production. ROS scavenging with Trolox depleted the Mn oxidation, and ROS-stimulant increased the Mn precipitation in A. oxydans. Increasing the Mn(II) concentration caused a reduction in the membrane potential and bacterial viability, which resulted in Mn precipitation on the bacteria surface. In conclusion, bacterial ROS production serves as a complementary non-enzymatic temperature-dependent mechanism for Mn(II) oxidation as a response in warming environments.

Rhodochrosite Oxidation by Dissolved Oxygen and the Formation of Mn Oxide Product: The Impact of Goethite as a Foreign Solid Substrate.

Rhodochrosite conversion to Mn (oxyhydr)oxides significantly affects the fate and transport of various substances in the environment. We examined rhodochrosite oxidation by dissolved oxygen and the oxidation product formation with an emphasis on the effects of goethite substrate. Without goethite, rhodochrosite oxidation was slow as no detectable change was observed for 28 d with microscopic and spectroscopic analyses, except a minor change in X-ray diffraction. Interestingly, by contrast, it was greatly accelerated and completed in 7 d in the presence of goethite, resulting in the heteroepitaxial growth of groutite (α-MnOOH)-like Mn oxides on the goethite (α-FeOOH) tip surfaces. The formation of this secondary Mn oxide likely induced the acidification of the microenvironment in the vicinity of rhodochrosite particles and thereby promoted their dissolution. Subsequently, their oxidative conversion to the Mn oxide was expedited by the surface catalyzed Mn(II) oxidation on the goethite tip. Our results revealed that goethite as a foreign substrate imparts a decisive control on not only the rate but also the type of the reaction product of rhodochrosite oxidation. This study presents a new insight into the geochemical roles of foreign particles on the dynamics of redox-sensitive solid phases in the environment.

Antimonate Controls Manganese(II)-Induced Transformation of Birnessite at a Circumneutral pH.

Manganese (Mn) oxides, such as birnessite (δ-MnO2), are ubiquitous mineral phases in soils and sediments that can interact strongly with antimony (Sb). The reaction between birnessite and aqueous Mn(II) can induce the formation of secondary Mn oxides. Here, we studied to what extent different loadings of antimonate (herein termed Sb(V)) sorbed to birnessite determine the products formed during Mn(II)-induced transformation (at pH 7.5) and corresponding changes in Sb behavior. In the presence of 10 mM Mn(II)aq, low Sb(V)aq (10 μmol L-1) triggered the transformation of birnessite to a feitknechtite (β-Mn(III)OOH) intermediary phase within 1 day, which further transformed into manganite (γ-Mn(III)OOH) over 30 days. Medium and high concentrations of Sb(V)aq (200 and 600 μmol L-1, respectively) led to the formation of manganite, hausmannite (Mn(II)Mn(III)2O4), and groutite (αMn(III)OOH). The reaction of Mn(II) with birnessite enhanced Sb(V)aq removal compared to Mn(II)-free treatments. Antimony K-edge extended X-ray absorption fine structure (EXAFS) spectroscopy revealed that heterovalent substitution of Sb(V) for Mn(III) occurred within the secondary Mn oxides, which formed via the Mn(II)-induced transformation of Sb(V)-sorbed birnessite. Overall, Sb(V) strongly influenced the products of the Mn(II)-induced transformation of birnessite, which in turn attenuated Sb mobility via incorporation of Sb(V) within the secondary Mn oxide phases.

Renal outcomes of idiopathic and atypical membranous nephropathy in adult Chinese patients: a single center retrospective cohort study

BackgroundMembranous nephropathy (MN) is mainly classified into idiopathic MN (iMN) and secondary MN in etiology. In recent years, a new kind of membranous nephropathy, atypical membranous nephropathy (aMN) which shows “full house” in immunofluorescence but without definite etiology was paid more attention. In a single center cohort, the renal outcomes of iMN and aMN were compared.MethodsiMN and aMN patients were selected from renal pathology databank from January 2006 to December 2015. Patients’ demographics, laboratory values, induction regimens and patients’ responses were recorded. Specially, creatinine, eGFR, albumin and 24 h urinary protein excretion were recorded at 6th month after the induction of immunosuppressive (IS) treatment and at the end of follow up. Complete proteinuria remission was defined as urinary protein < 0.3 g/d, partial proteinuria remission was defined as urinary protein between 0.3 g/d ~ 3.5 g/d and decreased > 50 % from the baseline. The primary outcome was worsening renal function, defined as a 30 % or more decrease in eGFR or end-stage renal disease (eGFR < 15ml/min/1.73m2). COX proportional hazard models were used to test if aMN was a risk factor of worsening renal function compared with iMN.ResultsThere were 298 patients diagnosed with MN and followed in our center for 1 year or more, including 145 iMN patients with an average follow-up time of 4.5 ± 2.6 years, and 153 aMN patients with 4.1 ± 2.0 years (p = 0.109). The average age of iMN patients was older than aMN patients (56.1 ± 12.2 versus 47.2 ± 16.2 years old, p < 0.001). There were 99 iMN patients and 105 aMN patients with nephrotic range proteinuria and without previous immunosuppressive treatment. 93 (93.9 %) and 95 (90.5 %) patients underwent immunosuppressive treatment in iMN and aMN group, and there was no significant difference of the overall proteinuria remission rates at 6th month (59.1 % vs. 52.0 %, p = 0.334) and endpoint (73.7 % vs. 69.5 %, p = 0.505) between the two groups. 25 (25.3 %) patients in iMN group and 21 (20.0 %) patients in aMN group reached primary endpoint (X2 = 0.056, p = 0.812). Multivariate COX regression showed that after demographics, baseline laboratory values and remission status at 6th month were adjusted, aMN group had similar renal outcome compared with iMN group, the HR of primary outcome was 0.735 (95 % CI 0.360 ~ 1.503, p = 0.399).ConclusionsThe proteinuria remission rates and renal outcomes were similar in iMN and aMN patients after covariables were adjusted.