Pristine/magnesium-loaded biochar and ZVI affect rice grain arsenic speciation and cadmium accumulation through different pathways in an alkaline paddy soil.

Cadmium (Cd) and arsenic (As) co-contamination has threatened rice production and food safety. It is challenging to mitigate Cd and As contamination in rice simultaneously due to their opposite geochemical behaviors. Mg-loaded biochar with outstanding adsorption capacity for As and Cd was used for the first time to remediate Cd/As contaminated paddy soils. In addition, the effect of zero-valent iron (ZVI) on grain As speciation accumulation in alkaline paddy soils was first investigated. The effect of rice straw biochar (SC), magnesium-loaded rice straw biochar (Mg/SC), and ZVI on concentrations of Cd and As speciation in soil porewater and their accumulation in rice tissues was investigated in a pot experiment. Addition of SC, Mg/SC and ZVI to soil reduced Cd concentrations in rice grain by 46.1%, 90.3% and 100%, and inorganic As (iAs) by 35.4%, 33.1% and 29.1%, respectively, and reduced Cd concentrations in porewater by 74.3%, 96.5% and 96.2%, respectively. Reductions of 51.6% and 87.7% in porewater iAs concentrations were observed with Mg/SC and ZVI amendments, but not with SC. Dimethylarsinic acid (DMA) concentrations in porewater and grain increased by a factor of 4.9 and 3.3, respectively, with ZVI amendment. The three amendments affected grain concentrations of iAs, DMA and Cd mainly by modulating their translocation within plant and the levels of As(III), silicon, dissolved organic carbon, iron or Cd in porewater. All three amendments (SC, Mg/SC and ZVI) have the potential to simultaneously mitigate Cd and iAs accumulation in rice grain, although the pathways are different.

Bioactive nanocomposite hydrogel enhances postoperative immunotherapy and bone reconstruction for osteosarcoma treatment.

Osteosarcoma, a malignant bone tumor often characterized by high hedgehog signaling activity, residual tumor cells, and substantial bone defects, poses significant challenges to both treatment response and postsurgical recovery. Here, we developed a nanocomposite hydrogel for the sustained co-delivery of bioactive magnesium ions, anti-PD-L1 antibody (αPD-L1), and hedgehog pathway antagonist vismodegib, to eradicate residual tumor cells while promoting bone regeneration post-surgery. In a mouse model of tibia osteosarcoma, this hydrogel-mediated combination therapy led to remarkable tumor growth inhibition and hence increased animal survival by enhancing the activity of tumor-suppressed CD8+ T cells. Meanwhile, the implanted hydrogel improved the microenvironment of osteogenesis through long-term sustained release of Mg2+, facilitating bone defect repair by upregulating the expression of osteogenic genes. After 21 days, the expression levels of ALP, COL1, RUNX2, and BGLAP in the Vis-αPD-L1-Gel group were approximately 4.1, 5.1, 5.5, and 3.4 times higher than those of the control, respectively. We believe that this hydrogel-based combination therapy offers a potentially valuable strategy for treating osteosarcoma and addressing the tumor-related complex bone diseases.

Maintenance of magnesium homeostasis by NUF2 promotes protein synthesis and anaplastic thyroid cancer progression.

Thyroid cancer is the most frequently observed endocrine-related malignancy among which anaplastic thyroid cancer (ATC) is the most fatal subtype. The synthesis of protein is active to satisfy the rapid growth of ATC tumor, but the mechanisms regulating protein synthesis are still unknown. Our research revealed that kinetochore protein NUF2 played an essential role in protein synthesis and drove the progression of ATC. The prognosis of patients with thyroid carcinoma was positively correlated with high NUF2 expression. Depletion of NUF2 in ATC cells notably inhibited the proliferation and induced apoptosis, while overexpression of NUF2 facilitated ATC cell viability and colony formation. Deletion of NUF2 significantly suppressed the growth and metastasis of ATC in vivo. Notably, knockdown of NUF2 epigenetically inhibited the expression of magnesium transporters through reducing the abundance of H3K4me3 at promoters, thereby reduced intracellular Mg2+ concentration. Furthermore, we found the deletion of NUF2 or magnesium transporters significantly inhibited the protein synthesis mediated by the PI3K/Akt/mTOR pathway. In conclusion, NUF2 functions as an emerging regulator for protein synthesis by maintaining the homeostasis of intracellular Mg2+, which finally drives ATC progression.

Is there an Association between Dietary Micronutrients Intake and Bone Fractures among Malaysian Reproductive-Age Women? The PURE Malaysia Study.

Background: Bone fractures represent a significant health issue and impose a considerable burden on healthcare systems globally. However, data pertaining to bone fractures, especially among reproductive-age women in Malaysia, are very limited. Micronutrients like calcium, magnesium and phosphorus play vital roles in bone health, influencing bone mineral density and fracture risk. The objective of this study was to determine the prevalence of bone fractures among reproductive-age women and the association with dietary micronutrient intakes. Methods: In this cross-sectional study, a total of 1,730 participants of reproductive-age women from the Malaysia Prospective Urban and Rural Epidemiological (PURE) study were recruited. The participants' dietary intakes were assessed using a validated semi-quantitative food frequency questionnaire (FFQ). Selected micronutrients in the participants' diets were calculated using the Malaysian food composition and the US Department of Agriculture food composition databases. The association between micronutrient intakes, comorbidities and physical activity levels with bone fractures were evaluated to identify predictors of bone fractures among reproductive-age women. Results: The prevalence of bone fractures among Malaysian reproductive-age women was low (3.7%). The multiple logistic regression analysis showed that none of the micronutrients was associated with bone fractures. However, factors of diabetes and passive smoking in this study showed 2.6- and 4.0-times-higher odds of having bone fractures, respectively (AOR 2.580; 95% CI: 1.173-5.672) and (AOR 4.012; 95% CI: 2.265-7.107). Conclusions: It was found that the majority of women in this study were taking lower micronutrient intakes of calcium, magnesium, and vitamin K than the Malaysia recommended nutrient intakes (RNI). Although this study showed that a low micronutrient intake is not significantly associated with bone fractures, it is recommended that future studies focus on controlled trials or prospective data analyses to establish causal relationships and the optimal micronutrient requirements for maintaining strong and healthy bones in women of reproductive age.

Evaluation of serum vitamin B12 and D, iron, ferritin, folate, calcium, phosphorus and magnesium levels in children in palliative care clinic: a single-center cross-sectional study.

BACKGROUND: Pediatric palliative care (PPC) patients are at an elevated risk of malnutrition. Nutritional inadequacy can also cause micronutrient deficiencies. These factors can lead to weight loss, stunted growth, and poor quality of life. Despite the prevalence of these issues, limited research exists in the micronutrient status of PPC patients. The purpose of this study was to determine the vitamin B12 and D, iron, ferritin, folate, calcium, phosphorus, and magnesium levels of PPC patients to contribute to a better understanding of their micronutrient needs as well as the appropriate management of diet and treatment approaches. METHODS: This was a single-center observational cross-sectional retrospective study. This study evaluated the levels of vitamin B12, 25-hydroxyvitamin D, iron, ferritin, folate, calcium, phosphorus, and magnesium in PPC patients. The patients were classified according to the Chronic Complex Conditions (CCC) v2 and then compared. RESULTS: A total of 3,144 micronutrient data points were collected from 822 hospitalizations of 364 patients. At least one micronutrient deficiency was identified in 96.9% of the patients. The most prevalent deficiencies were observed for iron, calcium, and phosphate. In addition, 25-hydroxyvitamin D deficiency was observed in one-third of patients. Calcium, magnesium, phosphorus, folate, and 25-hydroxyvitamin D were negatively correlated with age. CONCLUSION: The results of this study indicate that micronutrient deficiencies are highly prevalent in PPC patients. These findings have the potential to contribute to improvements in the nutritional and therapeutic management of patients.

High-level succinic acid production by overexpressing a magnesium transporter in Mannheimia succiniciproducens.

Succinic acid (SA), a dicarboxylic acid of industrial importance, can be efficiently produced by metabolically engineered Mannheimia succiniciproducens. Although the importance of magnesium (Mg2+) ion on SA production has been evident from our previous studies, the role of Mg2+ ion remains largely unexplored. In this study, we investigated the impact of Mg2+ ion on SA production and developed a hyper-SA producing strain of M. succiniciproducens by reconstructing the Mg2+ ion transport system. To achieve this, optimal alkaline neutralizer comprising Mg2+ ion was developed and the physiological effect of Mg2+ ion was analyzed. Subsequently, the Mg2+ ion transport system was reconstructed by introducing an efficient Mg2+ ion transporter from Salmonella enterica. A high-inoculum fed-batch fermentation of the final engineered strain produced 152.23 ± 0.99 g/L of SA, with a maximum productivity of 39.64 ± 0.69 g/L/h. These findings highlight the importance of Mg2+ ions and transportation system optimization in succinic acid production by M. succiniciproducens.

Biodegradable magnesium based metal materials inhibit the growth of cervical cancer cells.

Traditional chemotherapy drugs for cervical cancer often cause significant toxic side effects and drug resistance problems, highlighting the urgent need for more innovative and effective treatment strategies. Magnesium alloy is known to be degradable and biocompatible. The release of degradation products Mg2+, OH-, and H2 from magnesium alloy can alter the tumor microenvironment, providing potential anti-tumor properties. We explored the innovative use of magnesium alloy biomaterials in the treatment of cervical cancer, investigating how various concentrations of Mg2+ on the proliferation and cell death of cervical cancer cells. The results revealed that varying concentrations of Mg2+ significantly inhibited cervical cancer by arresting the cell cycle in the G0/G1 phase and inducing apoptosis in SiHa cells, effectively reducing tumor cell proliferation. In vivo experiments demonstrated that 20 mM Mg2+ group had the smallest tumor volume, exhibiting a potent inhibitory effect on the biological characteristics of cervical cancer. This enhances the therapeutic potential of this biomaterial as a local anti-tumor therapy and lays a theoretical foundation for the potential application of magnesium in the treatment of cervical cancer.

"The effects of non-surgical periodontal treatment plus zinc and magnesium supplementation on oxidative stress and antioxidants enzymes in type 2 diabetes patients: a quasi-experimental study".

BACKGROUND: Periodontal Disease (PD) associated with Type 2 Diabetes Mellitus (T2DM) is a chronic condition that affects the oral cavity of people living with T2DM. The mechanisms of the interaction between type 2 Diabetes Mellitus and Periodontal diseases are complex and involve multiple pathophysiological pathways related to the systemic inflammatory process and oxidative stress. Non-surgical periodontal treatment (NSTP) is considered the standard for the management of this disease; however, patients with systemic conditions such as type 2 Diabetes Mellitus do not seem to respond adequately. For this reason, the use of complementary treatments has been suggested to support non-surgical periodontal treatment to reduce the clinical consequences of the disease and improve the systemic conditions of the patient. The use of zinc gluconate and magnesium oxide as an adjunct to non-surgical periodontal treatment and its effects on periodontal clinical features and oxidative stress in patients with Periodontal diseases -type 2 Diabetes Mellitus is poorly understood. METHODS: A quasi-experimental study was performed in patients with periodontal diseases associated with T2DM. Initially, 45 subjects who met the selection criteria were included. 19 were assigned to a control group [non-surgical periodontal treatment] and 20 to the experimental group (non-surgical periodontal treatment + 500 mg of magnesium oxide and 50 mg of zinc gluconate for oral supplementation for 30 days) and the data of 6 patients were eliminated. Sociodemographic characteristics, physiological factors, biochemical parameters, and clinical features of periodontal diseases were assessed. RESULTS: In this research a change in periodontal clinical characteristics was observed, which has been associated with disease remission. Additionally, a shift in MDA levels was presented for both groups. Furthermore, the supplementation group showed an increase in antioxidant enzymes when compared to the group that only received NSPT. CONCLUSION: The use of Zinc gluconate and magnesium oxide can serve as a complementary treatment to non-surgical periodontal treatment, that supports the remission of PD as a result of regulation-reduction of oxidative biomarkers and increase in antioxidant enzymes activity. TRIAL REGISTRATION: https://www.isrctn.com ISRCTN 14,092,381. September 13º 2023. Retrospective Registration.

Effect of hematoma on early degradation behavior of magnesium after implantation.

The corrosion of magnesium (Mg)-based bioabsorbable implanting devices is influenced by implantation environment which dynamically changes by biological response including wound healing. Understanding the corrosion mechanisms along the healing process is essential for the development of Mg-based devices. In this study, a hematoma model was created in a rat femur to analyze Mg corrosion with hematoma in the early stage of implantation. Pure Mg specimen (99.9%,ϕ1.2 × 6 mm) was implanted in rat femur under either hematoma or non-hematoma conditions. After a designated period of implantation, the specimens were collected and weighed. The insoluble salts formed on the specimen surfaces were analyzed using scanning electron microscopy, energy-dispersive x-ray spectroscopy, and Raman spectroscopy on days 1, 3, and 7. The results indicate that hematomas promote Mg corrosion and change the insoluble salt precipitation. The weight loss of the hematoma group (27.31 ± 5.91 µg mm-2) was significantly larger than that of the non-hematoma group (14.77 ± 3.28 µg mm-2) on day 7. In the non-hematoma group, carbonate and phosphate were detected even on day 1, but the only latter was detected on day 7. In the hematoma group, hydroxide was detected on day 1, followed by the formation of carbonate and phosphate on days 3 and 7. The obtained results suggest the hypoxic and acidic microenvironment in hematomas accelerates the Mg corrosion immediately after implantation, and the subsequent hematoma resorption process leads to the formation of phosphate and carbonate with organic molecules. This study revealed the risk of hematomas as an acceleration factor of the corrosion of Mg-based devices leading to the early implant failure. It is important to consider this risk in the design of Mg-based devices and to optimize surgical procedures controlling hemorrhage at implantation and reducing unexpected bleeding after surgery.

Migration of copper(II) ions in humic systems-effect of incorporated calcium(II), magnesium(II), and iron(III) ions.

The mobility of heavy metals in natural soil systems can be affected by the properties and compositions of those systems: the content and quality of organic matter as well as the character of inorganic constituents. In this work, the diffusion of copper(II) ions in humic hydrogels with incorporated calcium(II), magnesium(II), and iron(III) ions was investigated. The methods of instantaneous planar source and of constant source were used. Experimental data yielded the time development of the concentration in hydrogels and the values of effective diffusion coefficients. The coefficients include both the influence of the hydrogel structure and the interaction of diffusing particles with the hydrogel. Our results showed that the presence of natural metal ions such as calcium, magnesium, or iron can strongly affect the diffusivity of copper in humic systems. They indicate that the mobility of copper ions depends on their concentration. The mobility can be supported by higher contents of copper in the system. While the incorporation of Ca and Mg resulted in the decrease in the diffusivity of copper ions, the incorporation of Fe(III) into humic hydrogel resulted in an increase in the diffusivity of Cu(II) in the hydrogel in comparison with pure humic hydrogel.

Integrative approach to mitigate chromium toxicity in soil and enhance antioxidant activities in rice (Oryza sativa L.) using magnesium-iron nanocomposite and Staphylococcus aureus strains.

Pollutants in soil, particularly chromium (Cr), pose high environmental and health risks due to their persistence, bioavailability, and potential for causing toxicity. Cr impairment in plants act as a deleterious environmental pollutant that enters the food chain and eventually disturbs human health. Current study demonstrated the potential of integrative foliar application of magnesium-iron (Mg + Fe) nanocomposite with Staphylococcus aureus strains to alleviate Cr toxicity in rice (Oryza sativa) crops by improving yield and defense system. Growth and yield traits such as shoot length (15%), root length (17%), shoot fresh weight (14%), shoot dry weight (9%), root fresh weight (23%), root dry weight (7%), number of tillers (33%), number of grains (10%) and spike length (13%) improved by combined application of Mg + Fe (20 mg L-1) nanocomposite and S. aureus strains with Cr (110 mg kg-1), compared to when applied alone. Mutual Mg + Fe and S. aureus strains application augmented the SPAD value (9%), total chlorophyll (11%), a (12%), b (17%), and carotenoids (32%), with Cr (110 mg kg-1), compared to alone. Malondialdehyde (13%), hydrogen peroxide (H2O2) (11%), and electrolyte leakage (7%) were significantly regulated in shoots with combined Mg + Fe and S. aureus strains application with Cr (110 mg kg-1) contrasted to alone. Peroxidase (20%), superoxide dismutase (17%), ascorbate peroxidase (18%), and catalase (20%) were increased in shoots with combined Mg + Fe and S. aureus strains application with Cr (110 mg kg-1) in comparison to alone. The combined application of Mg + Fe (20 mgL-1) nanocomposite and S. aureus strains with Cr (110 mg kg-1) enhanced the macro-micronutrients in shoots compared to alone. Cr accumulation in roots (21%), shoots (25%), and grains (47%) were significantly reduced under Cr (110 mg kg-1) with combined Mg + Fe and S. aureus strains application, compared to alone. Subsequently, applying combined Mg + Fe and S. aureus strains is a sustainable solution to boost crop production under Cr toxicity.

Low Calcium-High Magnesium Krebs-Henseleit Solution Combined with Adenosine and Lidocaine Improved Rat Aortic Function and Structure Following Cold Preservation.

Background and objectives: The main problem of vascular preservation is the maintenance of vessel graft quality and function following extended storage. Conventional preservation solutions such as histidine-tryptophan-ketoglutarate (HTK) solution, Phosphate-Buffer Solution (PBS), or sodium chloride 0.9% has been shown to be inadequate in preserving vascular physiological function after 3 days of cold storage. This study aimed to evaluate whether adenosine and lidocaine (AL) in a modified Krebs-Henseleit (KH) solution can preserve the function and histological structure of rat aortic rings after 6 days. Materials and Methods: Thirty-five aortic rings from male Wistar rats (200-300 g) were harvested and immediately immersed in one of the assigned cold preservation solutions: standard KH, modified KH (mod KH) with lower calcium (Ca2+) and higher magnesium content (Mg2+) with or without adenosine and lidocaine (mod KH-AL), and modified KH with AL, insulin, and melatonin (Mod KH-ALMI). The contraction and relaxation function of the aortic rings were examined using an isometric force transducer after 6 days of cold preservation. Hematoxylin and eosin staining were used to analyze the rings' histological structure. Results: Vascular contraction and relaxation functions were severely affected after a 6-day cold storage period in standard KH. Modifying the KH solution by reducing the Ca2+ and increasing the Mg2+ levels greatly recovered the vessel functions. The addition of AL or ALMI to the modified KH did not further recover vascular contractility. However, only the addition of AL to the modified KH increased the ACh-induced relaxation at 6 days when compared to the conventional KH, suggesting that endothelium preservation is improved. From histological analysis, it was found that the addition of AL but not ALMI further improved the endothelial lining and the structure of the elastic membrane layers of the preserved vessels after 6 days of cold preservation. Conclusions: The addition of AL to low calcium-high magnesium KH solution significantly enhanced endothelial preservation and improved endothelial-induced relaxation of preserved vessels after 6 days of cold storage.

Magnesium induced structural reorganization in the active site of adenylate kinase.

Phosphoryl transfer is a fundamental reaction in cellular signaling and metabolism that requires Mg2+ as an essential cofactor. While the primary function of Mg2+ is electrostatic activation of substrates, such as ATP, the full spectrum of catalytic mechanisms exerted by Mg2+ is not known. In this study, we integrate structural biology methods, molecular dynamic (MD) simulations, phylogeny, and enzymology assays to provide molecular insights into Mg2+-dependent structural reorganization in the active site of the metabolic enzyme adenylate kinase. Our results demonstrate that Mg2+ induces a conformational rearrangement of the substrates (ATP and ADP), resulting in a 30° adjustment of the angle essential for reversible phosphoryl transfer, thereby optimizing it for catalysis. MD simulations revealed transitions between conformational substates that link the fluctuation of the angle to large-scale enzyme dynamics. The findings contribute detailed insight into Mg2+ activation of enzymes and may be relevant for reversible and irreversible phosphoryl transfer reactions.

Structural basis of transcription: RNA polymerase II substrate binding and metal coordination using a free-electron laser.

Catalysis and translocation of multisubunit DNA-directed RNA polymerases underlie all cellular mRNA synthesis. RNA polymerase II (Pol II) synthesizes eukaryotic pre-mRNAs from a DNA template strand buried in its active site. Structural details of catalysis at near-atomic resolution and precise arrangement of key active site components have been elusive. Here, we present the free-electron laser (FEL) structures of a matched ATP-bound Pol II and the hyperactive Rpb1 T834P bridge helix (BH) mutant at the highest resolution to date. The radiation-damage-free FEL structures reveal the full active site interaction network, including the trigger loop (TL) in the closed conformation, bonafide occupancy of both site A and B Mg2+, and, more importantly, a putative third (site C) Mg2+ analogous to that described for some DNA polymerases but not observed previously for cellular RNA polymerases. Molecular dynamics (MD) simulations of the structures indicate that the third Mg2+ is coordinated and stabilized at its observed position. TL residues provide half of the substrate binding pocket while multiple TL/BH interactions induce conformational changes that could allow translocation upon substrate hydrolysis. Consistent with TL/BH communication, a FEL structure and MD simulations of the T834P mutant reveal rearrangement of some active site interactions supporting potential plasticity in active site function and long-distance effects on both the width of the central channel and TL conformation, likely underlying its increased elongation rate at the expense of fidelity.

Subtype-Specific Ligand Binding and Activation Gating in Homomeric and Heteromeric P2X Receptors.

P2X receptors are ATP-activated, non-specific cation channels involved in sensory signalling, inflammation, and certain forms of pain. Investigations of agonist binding and activation are essential for comprehending the fundamental mechanisms of receptor function. This encompasses the ligand recognition by the receptor, conformational changes following binding, and subsequent cellular signalling. The ATP-induced activation of P2X receptors is further influenced by the concentration of Mg2+ that forms a complex with ATP. To explore these intricate mechanisms, two new fluorescently labelled ATP derivatives have become commercially available: 2-[DY-547P1]-AHT-ATP (fATP) and 2-[DY-547P1]-AHT-α,ßMe-ATP (α,ßMe-fATP). We demonstrate a subtype-specific pattern of ligand potency and efficacy on human P2X2, P2X3, and P2X2/3 receptors with distinct relations between binding and gaiting. Given the high in vivo concentrations of Mg2+, the complex formed by Mg2+ and ATP emerges as an adequate ligand for P2X receptors. Utilising fluorescent ligands, we observed a Mg2+-dependent reduction in P2X2 receptor activation, while binding remained surprisingly robust. In contrast, P2X3 receptors initially exhibited decreased activation at high Mg2+ concentrations, concomitant with increased binding, while the P2X2/3 heteromer showed a hybrid effect. Hence, our new fluorescent ATP derivatives are powerful tools for further unravelling the mechanism underlying ligand binding and activation gating in P2X receptors.

Graded Modulation of Inflammation by Metal Ion-Coordinated Peptide-Based Hydrogel Chemical Regulators Promotes Tendon-Bone Junction Regeneration.

After rotator cuff injuries, uncontrolled inflammation hinders tendon-bone junction regeneration and induces scar formation in situ. Therefore, precisely controlling inflammation could be a solution to accelerate tendon-bone junction regeneration. In this study, we synthesized a peptide-metal ion complex hydrogel with thermosensitive capability that can be used as a hydrogel chemical regulator. By the coordination complex between Mg2+ and BMP-12, the free and coordinated Mg2+ can be programmability released from the hydrogel. The fast release of free Mg2+ can prevent inflammation at the early stage of injuries, according to the results of RT-qPCR and immunofluorescence staining. Then, the coordinated Mg2+ was slowly released from the hydrogel and provided an anti-inflammatory environment for tendon-bone junction regeneration in the long term. Finally, the hydrogel demonstrated enhanced therapeutic effects in a rat rotator cuff tear model. Overall, the Mg2+/BMP-12 peptide-metal ion complex-based hydrogel effectively addresses the regenerative requirements of the tendon-bone junction across various stages by graded modulating inflammation.

Multifunctional Sr,Mg-Doped Mesoporous Bioactive Glass Nanoparticles for Simultaneous Bone Regeneration and Drug Delivery.

Mesoporous bioactive glass nanoparticles (MBGNs) doped with therapeutical ions present multifunctional systems that enable a synergistic outcome through the dual delivery of drugs and ions. The aim of this study was to evaluate influence of co-doping with strontium and magnesium ions (SrMg-MBGNs) on the properties of MBGNs. A modified microemulsion-assisted sol-gel synthesis was used to obtain particles, and their physicochemical properties, bioactivity, and drug-loading/release ability were evaluated. Indirect biological assays using 2D and 3D cell culture models on human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and endothelial EA.hy926 cells, respectively, were used to determine biocompatibility of MBGNs, their influence on alkaline phosphatase (ALP) production, calcium deposition, and cytoskeletal organization. Results showed that Sr,Mg-doping increased pore volume and solubility, and changed the mesoporous structure from worm-like to radial-dendritic, which led to a slightly accelerated drug release compared to pristine MBGNs. Biological assays confirmed that particles are biocompatible, and have ability to slightly induce ALP production and calcium deposition of hBM-MSCs, as well as to significantly improve the proliferation of EA.hy926 compared to biochemical stimulation via vascular endothelial growth factor (VEGF) administration or regular media. Fluorescence staining revealed that SrMg-MBGNs had a similar effect on EA.hy926 cytoskeletal organization to the VEGF group. In conclusion, Sr,Mg-MBGNs might be considered promising biomaterial for biomedical applications.

Metals and other ligands balance carbon fixation and photorespiration in chloroplasts.

The behavior of many plant enzymes depends on the metals and other ligands to which they are bound. A previous study demonstrated that tobacco Rubisco binds almost equally to magnesium and manganese and rapidly exchanges one metal for the other. The present study characterizes the kinetics of Rubisco and the plastidial malic enzyme when bound to either metal. When Rubisco purified from five C3 species was bound to magnesium rather than manganese, the specificity for CO2 over O2, (Sc/o) increased by 25% and the ratio of the maximum velocities of carboxylation / oxygenation (Vcmax/Vomax) increased by 39%. For the recombinant plastidial malic enzyme, the forward reaction (malate decarboxylation) was 30% slower and the reverse reaction (pyruvate carboxylation) was three times faster when bound to manganese rather than magnesium. Adding 6-phosphoglycerate and NADP+ inhibited carboxylation and oxygenation when Rubisco was bound to magnesium and stimulated oxygenation when it was bound to manganese. Conditions that favored RuBP oxygenation stimulated Rubisco to convert as much as 15% of the total RuBP consumed into pyruvate. These results are consistent with a stromal biochemical pathway in which (1) Rubisco when associated with manganese converts a substantial amount of RuBP into pyruvate, (2) malic enzyme when associated with manganese carboxylates a substantial portion of this pyruvate into malate, and (3) chloroplasts export additional malate into the cytoplasm where it generates NADH for assimilating nitrate into amino acids. Thus, plants may regulate the activities of magnesium and manganese in leaves to balance organic carbon and organic nitrogen as atmospheric CO2 fluctuates.

An injectable magnesium-loaded hydrogel releases hydrogen to promote osteoporotic bone repair via ROS scavenging and immunomodulation.

Background: The repair of osteoporotic bone defects remains challenging due to excessive reactive oxygen species (ROS), persistent inflammation, and an imbalance between osteogenesis and osteoclastogenesis. Methods: Here, an injectable H2-releasing hydrogel (magnesium@polyethylene glycol-poly(lactic-co-glycolic acid), Mg@PEG-PLGA) was developed to remodel the challenging bone environment and accelerate the repair of osteoporotic bone defects. Results: This Mg@PEG-PLGA gel shows excellent injectability, shape adaptability, and phase-transition ability, can fill irregular bone defect areas via minimally invasive injection, and can transform into a porous scaffold in situ to provide mechanical support. With the appropriate release of H2 and magnesium ions, the 2Mg@PEG-PLGA gel (loaded with 2 mg of Mg) displayed significant immunomodulatory effects through reducing intracellular ROS, guiding macrophage polarization toward the M2 phenotype, and inhibiting the IκB/NF-κB signaling pathway. Moreover, in vitro experiments showed that the 2Mg@PEG-PLGA gel inhibited osteoclastogenesis while promoting osteogenesis. Most notably, in animal experiments, the 2Mg@PEG-PLGA gel significantly promoted the repair of osteoporotic bone defects in vivo by scavenging ROS and inhibiting inflammation and osteoclastogenesis. Conclusions: Overall, our study provides critical insight into the design and development of H2-releasing magnesium-based hydrogels as potential implants for repairing osteoporotic bone defects.

Mechanism of phosphate release from actin filaments.

After ATP-actin monomers assemble filaments, the ATP's [Formula: see text]-phosphate is hydrolyzedwithin seconds and dissociates over minutes. We used all-atom molecular dynamics simulations to sample the release of phosphate from filaments and study residues that gate release. Dissociation of phosphate from Mg2+ is rate limiting and associated with an energy barrier of 20 kcal/mol, consistent with experimental rates of phosphate release. Phosphate then diffuses within an internal cavity toward a gate formed by R177, as suggested in prior computational studies and cryo-EM structures. The gate is closed when R177 hydrogen bonds with N111 and is open when R177 forms a salt bridge with D179. Most of the time, interactions of R177 with other residues occlude the phosphate release pathway. Machine learning analysis reveals that the occluding interactions fluctuate rapidly, underscoring the secondary role of backdoor gate opening in Pi release, in contrast with the previous hypothesis that gate opening is the primary event.