Concomitant urea stabilization and phosphorus recovery from source-separated fresh urine in magnesium anode-based peroxide-producing electrochemical cells.

In this study, we investigated the recovery of nitrogen (N) and phosphorus (P) from fresh source-separated urine with a novel electrochemical cell equipped with a magnesium (Mg) anode and carbon-based gas-diffusion cathode. Recovery of P, which exists primarily as phosphate (PO43-) in urine, was achieved through pH-driven precipitation. Maximizing N recovery requires simultaneous approaches to address urea and ammonia (NH3). NH3 recovery was possible through precipitation in struvite with soluble Mg supplied by the anode. Urea was stabilized with electrochemically synthesized hydrogen peroxide (H2O2) from the cathode. H2O2 concentrations and resulting urine pH were directly proportional to the applied current density. Concomitant NH3 and PO43- precipitation as struvite and urea stabilization via H2O2 electrosynthesis was possible at lower current densities, resulting in urine pH under 9.2. Higher current densities resulted in urine pH over 9.2, yielding higher H2O2 concentrations and more consistent stabilization of urea at the expense of NH3 recovery as struvite; PO43- precipitation still occurred but in the form of calcium phosphate and magnesium phosphate solids.

Impact of Magnesium and Ferritin Deficiency on Depression Among Adolescent Students.

BACKGROUND: Depression is considered the fourth-leading cause of health problems. It is the fourth-leading cause of health problems and disability, which causes 16% of the worldwide burden of disease and injury among adolescents. OBJECTIVE: The aim of the present study was to evaluate the possible association of magnesium (Mg) and ferritin deficiency with depression in adolescent students. PATIENTS AND METHODS: This case control study in secondary schools at Al-Ghanayem discrete. The total number included was 358 students. All were screened for depression by the Arabic version of the Beck questionnaire. The students who had positive score was selected as cases 86 and a matched same number of students with negative score was selected as controls. Serum level of ferritin and magnesium was measured in the 2 groups. RESULTS: There was statistically significant difference between the studied groups when comparing depression grade with each of ferritin and Mg Depressed group cases had lower mean values of ferritin and Mg. The ferritin cut-off level for the prediction of depression was (35.5 µg/dL, which had a sensitivity of 74.4% and a specificity of 75.6%. The magnesium cut-off levels for the prediction of depression were1.95 mg/dL and 104.5 ng/dL which had a sensitivity of 70% and 64%, respectively. CONCLUSION: There was a statistically significant negative correlation between depression severity and each of socio-economic status ferritin and Mg. Each of ferritin and Mg were predictors for depression.

Deciphering the function of the fifth class of Gα proteins: regulation of ionic homeostasis as unifying hypothesis.

Trimeric G proteins transduce signals from a superfamily of receptors and each G protein controls a wide range of cellular and systemic functions. Their highly conserved alpha subunits fall in five classes, four of which have been well investigated (Gs, Gi, G12, Gq). In contrast, the function of the fifth class, Gv is completely unknown, despite its broad occurrence and evolutionary ancient origin (older than metazoans). Here we show a dynamic presence of Gv mRNA in several organs during early development of zebrafish, including the hatching gland, the pronephros and several cartilage anlagen, employing in situ hybridisation. Next, we generated a Gv frameshift mutation in zebrafish and observed distinct phenotypes such as reduced oviposition, premature hatching and craniofacial abnormalities in bone and cartilage of larval zebrafish. These phenotypes could suggest a disturbance in ionic homeostasis as a common denominator. Indeed, we find reduced levels of calcium, magnesium and potassium in the larvae and changes in expression levels of the sodium potassium pump atp1a1a.5 and the sodium/calcium exchanger ncx1b in larvae and in the adult kidney, a major osmoregulatory organ. Additionally, expression of sodium chloride cotransporter slc12a3 and the anion exchanger slc26a4 is altered in complementary ways in adult kidney. It appears that Gv may modulate ionic homeostasis in zebrafish during development and in adults. Our results constitute the first insight into the function of the fifth class of G alpha proteins.

A2 milk: Bioaccessibility of essential minerals and the release of amino groups under static in vitro digestion conditions.

Alternative milk products such as A2 milk are gaining popular stand within consumer market, for their healthy profile and expected greater digestibility characteristics. However, total mineral content and its bioaccessible profile have lacked in studies through the years, even more because of their relevance in public health. The present study aimed to evaluate the mineral profile of commercial A2 bovine milk (AT) and estimate the bioaccessibility of calcium, phosphorus and magnesium using the INFOGEST protocol. Non-A2 samples (NAT) were evaluated for comparison purpose. The determination of Ca, Mg, Na and K was performed by FAAS and total P was quantified by colorimetric method. Total protein content was determined by Kjeldahl method. Free amino acids were quantified by OPA method along the in vitro digestion stages. Total content of Ca, Na and P exhibited equivalent results between samples, although A2 milk showed elevated levels of total Mg and K in the analyzed batches. AT showed protein content equivalent to NAT. In addition, levels of free NH2 were observed 2 times higher in AT, during the first hour of pancreatic phase in the intestinal digestion. Bioaccessibility of Ca showed equivalent percentages for AT (12-42 %) and NAT (10-39 %). The observed low values were possibly derived from interferences with saturated fatty acids and standardized electrolytes during digestion. Similar amounts of bioaccessible Mg were found for all milk samples (35-97 %), while A2 samples evidenced percentages of bioaccessible P exceeding 60 % across the three batches. Despite the health benefits associated to A2 milk, the study did not evidence clear distinction from non-A2 milk in terms of enhanced essential mineral solubility in digestive tract simulation, considering the association of greater digestibility expected for A2 milk.

The Use of a Checklist to Optimize Electrolyte Replacement in the ICU.

Electrolyte replacement protocols are routinely used in intensive care units (ICU) to guide magnesium replacement. Guided by serum levels, these protocols include no patient-specific factors despite a literature showing ICU patients routinely have significant deficits despite normal serum levels. The authors developed a checklist to help identify patients requiring more aggressive magnesium replacement than the electrolyte replacement protocol would provide. The checklist included risk factors for having significant magnesium deficits and for developing arrhythmias. The checklist was retrospectively applied to 364 medical ICU patients. Diabetic patients prescribed outpatient diuretics were defined as the highest-risk population. A total of 88% of patients in this subgroup had normal magnesium levels. Despite averaging 3.4 risk factors per patient, only 3 of 32 patients received magnesium. Applying the checklist would have suggested additional repletion for at least 85% of patients. A checklist can help identify ICU patients who may require more aggressive magnesium supplementation than protocols will provide.

Biochemical characterization of Bombyx mori Dicer-2 that dices double-stranded RNAs into 20-nt small RNA.

We detected enzymatic activity that generates 20-nucleotide (nt) RNA from double-stranded RNAs (dsRNAs) in crude extracts prepared from various silkworm (Bombyx mori) organs. The result using knocked-down cultured cells indicated that this dicing activity originated from B. mori Dicer-2 (BmDcr2). Biochemical analyses revealed that BmDcr2 preferentially cleaves 5'-phosphorylated dsRNAs at the 20-nt site-counted from the 5'-phosphorylated end-and required ATP and magnesium ions for the dicing reaction. This is the first report of the biochemical characterization of Dicer-2 in lepidopteran insects. This enzymatic property of BmDcr2 in vitro is consistent with the in vivo small interfering RNA profile in virus-infected silkworm cells.

Magnesium implantation as a continuous hydrogen production generator for the treatment of myocardial infarction in rats.

Molecular hydrogen is an emerging broad-spectrum antioxidant molecule that can be used to treat myocardial infarction (MI). However, with hydrogen inhalation, the concentration that can be reached within target organs is low and the duration of action is short, which makes it difficult to achieve high dose targeted delivery of hydrogen to the heart, seriously limiting the therapeutic potential of hydrogen for MI. As a result of reactions with the internal environment of the body, subcutaneous implantation of magnesium slices leads to continuous endogenous hydrogen production, leading to a higher hydrogen concentration and a longer duration of action in target organs. In this study, we propose magnesium implant-based hydrogen therapy for MI. After subcutaneous implantation of magnesium slices in the dorsum of rats, we measured hydrogen production and efficiency, and evaluated the safety of this approach. Compared with hydrogen inhalation, it significantly improved cardiac function in rats with MI. Magnesium implantation also cleared free radicals that were released as a result of mitochondrial dysfunction, as well as suppressing cardiomyocyte apoptosis.

The structural basis for 2'-5'/3'-5'-cGAMP synthesis by cGAS.

cGAS activates innate immune responses against cytosolic double-stranded DNA. Here, by determining crystal structures of cGAS at various reaction stages, we report a unifying catalytic mechanism. apo-cGAS assumes an array of inactive conformations and binds NTPs nonproductively. Dimerization-coupled double-stranded DNA-binding then affixes the active site into a rigid lock for productive metal•substrate binding. A web-like network of protein•NTP, intra-NTP, and inter-NTP interactions ensures the stepwise synthesis of 2'-5'/3'-5'-linked cGAMP while discriminating against noncognate NTPs and off-pathway intermediates. One divalent metal is sufficient for productive substrate binding, and capturing the second divalent metal is tightly coupled to nucleotide and linkage specificities, a process which manganese is preferred over magnesium by 100-fold. Additionally, we elucidate how mouse cGAS achieves more stringent NTP and linkage specificities than human cGAS. Together, our results reveal that an adaptable, yet precise lock-and-key-like mechanism underpins cGAS catalysis.

Harnessing solar power for enhanced photocatalytic degradation of coloured pollutants using novel Mg-doped-ZnFe2O4/S@g-C3N4 heterojunction: A facile hydrothermal synthesis approach.

The ability of heterogeneous photocatalysis to effectively remove organic pollutants from wastewater has shown great promise as a tool for environmental remediation. Pure zinc ferrites (ZnFe2O4) and magnesium-doped zinc ferrites (Mg@ZnFe2O4) with variable percentages of Mg (0.5, 1, 3, 5, 7, and 9 mol%) were synthesized via hydrothermal route and their photocatalytic activity was checked against methylene blue (MB) taken as a model dye. FTIR, XPS, BET, PL, XRD, TEM, and UV-Vis spectroscopy were used for the identification and morphological characterization of the prepared nanoparticles (NPs) and nanocomposites (NCs). The 7% Mg@ZnFe2O4 NPs demonstrated excellent degradation against MB under sunlight. The 7% Mg@ZnFe2O4 NPs were integrated with diverse contents (10, 50, 30, and 70 wt.%) of S@g-C3N4 to develop NCs with better activity. When the NCs were tested to degrade MB dye, it was revealed that the 7%Mg@ZnFe2O4/S@g-C3N4 NCs were more effective at utilizing solar energy than the other NPs and NCs. The synergistic effect of the interface formed between Mg@ZnFe2O4 and S@g-C3N4 was primarily responsible for the boosted photocatalytic capability of the NCs. The fabricated NCs may function as an effective new photocatalyst to remove organic dyes from wastewater.

Role of preoperative zinc, magnesium and budesonide gargles in Postoperative Sore Throat (POST) - a randomised control trial.

BACKGROUND: Post-operative sore throat (POST) has an incidence ranging from 21 to 80%. To prevent the development of POST, several pharmacological measures have been tried. Aim of this study was to compare the efficacy of preoperative zinc, magnesium and budesonide gargles in reducing the incidence and severity of POST in patients who underwent endotracheal intubation for elective surgeries. METHODS: We conducted a prospective, randomized, double-blind, controlled equivalence trial in 180 patients admitted for elective surgical procedures under general anaesthesia. Patients were randomised into three groups; group Z received 40 mg Zinc, group M received 250 mg Magnesium Sulphate and group B received 200 µg Budesonide in the form of 30 ml tasteless and colourless gargle solutions. Sore throat assessment and haemodynamic recording was done postoperatively at immediate recovery (0 h) and 2, 4, 6, 8, 12 and 24 h post-operatively. POST was graded on a four-point scale (0-3). RESULTS: POST score was comparable at all recorded time points i.e. 0,2,4,6,8,12 and 24 h. Maximum incidence was seen at 8 h in group B (33.3%) and the minimum incidence was at 24 h in group Z (10%) (p > 0.05). It was found that the incidence of POST was more in the surgeries lasting longer than 2 h in all groups. This difference was found to be statistically significant in Groups M and B. The incidence of POST was found to be comparable between laparoscopic and open procedures. CONCLUSION: Magnesium, zinc and budesonide have an equivocal effect in the prevention of POST at different time points. The incidence of sore throat increases significantly in surgeries lasting more than two hours if magnesium or budesonide have been used as premedicant. Duration of surgery is an independent predictor for POST. TRIAL REGISTRATION: CTRI/2021/05/033741 Date-24/05/2021(Clinical Trial Registry of India).

Physicomechanical, morphological and tribo-deformation characteristics of lightweight WC/AZ31B Mg-matrix biocomposites for hip joint applications.

Exploring high strength materials with a higher concentration of reinforcements in the alloy proves to be a challenging task. This research has explored magnesium-based composites (AZ31B alloy) with tungsten carbide reinforcements, enhancing strength for medical joint replacements via league championship optimisation. The primary objective is to enhance medical joint replacement biomaterials employing magnesium-based composites, emphasising the AZ31B alloy with tungsten carbide reinforcements. The stir casting method is utilised in the manufacture of magnesium matrix composites (MMCs), including varied percentages of tungsten carbide (WC). The mechanical characteristics, such as micro-hardness, tensile strength, and yield strength, have been assessed and compared with computational simulations. The wear studies have been carried out to analyse the tribological behaviour of the composites. Additionally, this study investigates the prediction of stress and the distribution of forces inside bone and joint structures, therefore offering significant contributions to the field of biomedical research. This research contemplates the use of magnesium-based MMCs for the discovery of biomaterials suitable for medical joint replacement. The study focuses on the magnesium alloy AZ31B, with particles ranging in size from 40 to 60 microns used as the matrix material. Moreover, the outcomes have revealed that when combined with MMCs based on AZ31B-magnesium matrix, the WC particle emerges as highly effective reinforcements for the fabrication of lightweight, high-strength biomedical composites. This study uses the league championship optimisation (LCO) approach to identify critical variables impacting the synthesis of Mg MMCs from an AZ31B-based magnesium alloy. The scanning electron microscopy (SEM) images are meticulously analysed to depict the dispersion of WC particulates and the interface among the magnesium (Mg) matrix and WC reinforcement. The SEM analysis has explored the mechanisms underlying particle pull-out, the characteristics of inter-particle zones, and the influence of the AZ31B matrix on the enhancement of the mechanical characteristics of the composites. The application of finite element analysis (FEA) is being used in order to make predictions regarding the distribution of stress and the interactions of forces within the model of the hip joint. This study has compared the physico-mechanical and tribological characteristics of WC to distinct combinations of 0%, 5%, 10% and 15%, and its impact on the performance improvements. SEM analysis has confirmed the findings' improved strength and hardness, particularly when 10%-15% of WC was incorporated. Following the incorporation of 10% of WC particles within Mg-alloy matrix, the outcomes of the study has exhibited enhanced strength and hardness, which furthermore has been evident by utilising SEM analysis. Using ANSYS, structural deformation and stress levels are predicted, along with strength characteristics such as additional hardness of 71 HRC, tensile strength of 140-150 MPa, and yield strength closer to 100-110 MPa. The simulations yield significant insights into the behaviour of the joint under various loading conditions, thus enhancing the study's significance in biomedical environments.

[Analysis of the Divalent Cation Blocking in Ion Channels by Crystal Structure and Molecular Dynamics Simulations].

Neural activity generates essential responses, such as thinking, memory formation, and muscle contraction. It is controlled by the well-coordinated activity of various cation-selective channels of the cell membrane. The divalent cation block plays an essential role in various tetrameric ion channels. For example, N-methyl-D-aspartic acid receptors, which are tetrameric ion channels involved in memory formation, are inhibited by magnesium ions. Divalent cations are thought to bind in the ion pathway of the ion channel and as a consequence block the channel current, however, direct observation of such a block has not been reported yet. As a consequence, the behavior of these blocking divalent cations remains poorly understood. NavAb, a similar tetrameric sodium channel cloned from Arcobacter butzleri, is one of the most structurally analyzed tetrameric channels that is not inhibited by divalent cations. In this study, we elucidated the molecular mechanism of the divalent cation block by reproducing the divalent cation block in NavAb. The X-ray crystal structure of divalent-cation-block mutants show electron density in the ion transmission pathway of the divalent cation blocked mutants, indicating that the mutations increasing the hydrophilicity of the inner vestibule of the pore domain enable a divalent cation to stack into the ion pathway. In molecular dynamics simulations, the stacked calcium ion repels the sodium ions near the channel lumen's entrance at the selective filter's bottom. These results suggest the primary process of the divalent cation block mechanism in tetrameric cation channels and suggest a process of functional acquisition in ion channel evolution.

Arthrospira platensis enriched with Cr(III), Mg(II), and Mn(II) ions improves insulin sensitivity and reduces systemic inflammation in equine metabolic affected horses.

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.

Microfluidic paper-based analytical device for simultaneous determination of calcium and magnesium ions in human serum.

BACKGROUND: Calcium and magnesium ions are highly abundant and important cations in human body. At the same time, both dyscalcemia and dysmagnesemia are frequently encountered in the clinical practice. As deficiency or excess of Ca(II) or Mg(II) can cause severe symptoms, determining these ions in serum is of great importance. Concentration of these ions in biological samples is typically assayed in clinical laboratories with the use of expensive and specialized equipment. Since those methods cannot be easily adapted for self-diagnosis purposes, there is a great need to develop a convenient tool for reliable determination of calcium and magnesium in serum at the point-of-care. RESULTS: The colorimetric methods employed for calcium and magnesium analysis were o-cresophtalein complexone assay and xylidyl blue assay, respectively. Analytical signal acquisition was accomplished using an ordinary flatbed scanner or smartphone and free software. For increased user-friendliness the device was optimized to perform simultaneous determination of calcium and magnesium ions in only 10 min. In the optimized conditions, the limit of detection for calcium ions was 0.09 mmol L-1, while for magnesium it was 0.04 mmol L-1. Determination of both ions requires only 4 µL of serum sample. The developed paper-based sensors were validated with control human serum samples and the obtained relative errors for majority of samples were below 20 %. SIGNIFICANCE: In this paper, a microfluidic paper-based analytical device for simultaneous determination of calcium and magnesium ions in human serum is reported for the first time. Additionally, this is also the first report on colorimetric determination in serum of any of these ions in paper-based format. Simultaneous detection of both ions allows for fast and user-friendly screening of disturbance in calcium and magnesium homeostasis.

Unraveling the Mechanisms Involved in the Beneficial Effects of Magnesium Treatment on Skin Wound Healing.

The skin wound healing process consists of hemostatic, inflammatory, proliferative, and maturation phases, with a complex cellular response by multiple cell types in the epidermis, dermis, and immune system. Magnesium is a mineral essential for life, and although magnesium treatment promotes cutaneous wound healing, the molecular mechanism and timing of action of the healing process are unknown. This study, using human epidermal-derived HaCaT cells and human normal epidermal keratinocyte cells, was performed to investigate the mechanism involved in the effect of magnesium on wound healing. The expression levels of epidermal differentiation-promoting factors were reduced by MgCl2, suggesting an inhibitory effect on epidermal differentiation in the remodeling stage of the late wound healing process. On the other hand, MgCl2 treatment increased the expression of matrix metalloproteinase-7 (MMP7), a cell migration-promoting factor, and enhanced cell migration via the MEK/ERK pathway activation. The enhancement of cell migration by MgCl2 was inhibited by MMP7 knockdown, suggesting that MgCl2 enhances cell migration which is mediated by increased MMP7 expression. Our results revealed that MgCl2 inhibits epidermal differentiation but promotes cell migration, suggesting that applying magnesium to the early wound healing process could be beneficial.

Nontraditional Roles of Magnesium Ions in Modulating Sav2152: Insight from a Haloacid Dehalogenase-like Superfamily Phosphatase from Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infection has rapidly spread through various routes. A genomic analysis of clinical MRSA samples revealed an unknown protein, Sav2152, predicted to be a haloacid dehalogenase (HAD)-like hydrolase, making it a potential candidate for a novel drug target. In this study, we determined the crystal structure of Sav2152, which consists of a C2-type cap domain and a core domain. The core domain contains four motifs involved in phosphatase activity that depend on the presence of Mg2+ ions. Specifically, residues D10, D12, and D233, which closely correspond to key residues in structurally homolog proteins, are responsible for binding to the metal ion and are known to play critical roles in phosphatase activity. Our findings indicate that the Mg2+ ion known to stabilize local regions surrounding it, however, paradoxically, destabilizes the local region. Through mutant screening, we identified D10 and D12 as crucial residues for metal binding and maintaining structural stability via various uncharacterized intra-protein interactions, respectively. Substituting D10 with Ala effectively prevents the interaction with Mg2+ ions. The mutation of D12 disrupts important structural associations mediated by D12, leading to a decrease in the stability of Sav2152 and an enhancement in binding affinity to Mg2+ ions. Additionally, our study revealed that D237 can replace D12 and retain phosphatase activity. In summary, our work uncovers the novel role of metal ions in HAD-like phosphatase activity.

A Patented Dietary Supplement (Hydroxy-Methyl-Butyrate, Carnosine, Magnesium, Butyrate, Lactoferrin) Is a Promising Therapeutic Target for Age-Related Sarcopenia through the Regulation of Gut Permeability: A Randomized Controlled Trial.

Adequate diet, physical activity, and dietary supplementation with muscle-targeted food for special medical purposes (FSMP) or dietary supplement (DS) are currently considered fundamental pillars in sarcopenia treatment. The aim of this study is to evaluate the effectiveness of a DS (containing hydroxy-methyl-butyrate, carnosine, and magnesium, for its action on muscle function and protein synthesis and butyrate and lactoferrin for their contribution to the regulation of gut permeability and antioxidant/anti-inflammation activity) on muscle mass (assessed by dual X-ray absorptiometry (DXA)), muscle function (by handgrip test, chair test, short physical performance battery (SPPB) test, and walking speed test), inflammation (tumor necrosis factor-alpha (TNF-a), C-reactive protein (CRP), and visceral adipose tissue (VAT)) and gut axis (by zonulin). A total of 59 participants (age 79.7 ± 4.8 years, body mass index 20.99 ± 2.12 kg/m2) were enrolled and randomly assigned to intervention (n = 30) or placebo (n = 28). The skeletal muscle index (SMI) significantly improved in the supplemented group compared to the placebo one, +1.02 (CI 95%: -0.77; 1.26), p = 0.001; a significant reduction in VAT was observed in the intervention group, -70.91 g (-13.13; -4.70), p = 0.036. Regarding muscle function, all the tests significantly improved (p = 0.001) in the supplemented group compared to the placebo one. CRP, zonulin, and TNF-alpha significantly decreased (p = 0.001) in intervention, compared to placebo, -0.74 mg/dL (CI 95%: -1.30; -0.18), -0.30 ng/mL (CI 95%: -0.37; -0.23), -6.45 pg/mL (CI 95%: -8.71; -4.18), respectively. This DS improves muscle mass and function, and the gut muscle has emerged as a new intervention target for sarcopenia.

Electron Microscopy for the Stability Assessment of Parenteral Nutrition Admixtures: Focus on Precipitation.

(1) Background: parenteral nutrition (PN) is indispensable for patients unable to receive oral or enteral feeding. However, the complexity of PN solutions presents challenges regarding stability and compatibility. Precipitation reactions may occur. The most frequent is the formation of calcium phosphate (Ca-P). The different factors influencing these reactions must be considered to ensure patient safety. (2) Methods: eight paediatric PN solutions were prepared, following standard protocols. Samples were stored at room temperature and in a refrigerator. Electron microscopy, coupled with energy dispersive X-ray spectroscopy (EDS), was employed. Precipitates were analysed for composition and morphology. (3) Results: precipitates were observed in all samples, even at day 0. Crystalline structures, predominantly composed of calcium or magnesium, sometimes associated with chlorine or phosphorus, were detected. Additionally, amorphous precipitates, contained heterogeneous compositions, including unexpected elements, were identified. (4) Conclusions: various precipitates, primarily calcium- or magnesium-based, can form in PN solutions, although it is not expected that they can form under the real conditions of use. Calcium oxalate precipitation has been characterised, but the use of organic calcium and phosphate salts appears to mitigate calcium phosphate precipitation. Electron microscopy provides interesting results on NP precipitation, but sample preparation may present technical limitations that affect the interpretation of the results.

Magnesium supplementation therapy to prevent cisplatin-induced acute nephrotoxicity in pediatric cancer: a randomized phase-2 trial.

BACKGROUND: The present study aimed to examine the effect of magnesium (Mg) supplementation on cisplatin-induced nephrotoxicity (CIN) in pediatric cancer patients. METHODS: The present phase-2, open-label, multicenter, randomized controlled trial enrolled patients aged less than 20 years who were scheduled to receive cisplatin-containing chemotherapy and randomly allocated them at a ratio of 1:1 to a Mg supplementation arm with even-numbered chemotherapy courses (arm AB) or another arm with odd-numbered courses (arm BA). Analysis objects were reconstructed into two groups depending on whether the chemotherapy course had Mg supplementation (group B) or not (group A). The primary outcome was the proportion of chemotherapy courses resulting in elevated serum creatinine per chemotherapy course. The secondary outcomes included efficacies evaluated using other biomarkers and the safety of the Mg supplementation. RESULTS: Twenty-eight patients were randomly allocated to either group (16 to arm AB and 12 to arm BA). The baseline characteristics of the groups were similar. There was no significant difference in the proportion of courses with increased serum creatinine between the groups (group A: 10% vs. group B: 6%; P = 0.465) nor was any significant difference observed in other biomarkers during any chemotherapy course. The Mg value during chemotherapy was significantly higher in group B than that in group A. No adverse events related to magnesium administration were observed. CONCLUSIONS: The study design, which treated a single chemotherapy course as a study object, failed to detect a statistically significant benefit of Mg supplementation for preventing CIN in pediatric cancer patients. TRIAL REGISTRATION: JRCT ( https://jrct.niph.go.jp/ ) Identifier UMIN000029215 jRCTs031180251. UMIN-CTR ( http://www.umin.ac.jp/icdr/index.html ) Identifier UMIN000029215.

The effect of pseudoknot base pairing on cotranscriptional structural switching of the fluoride riboswitch.

A central question in biology is how RNA sequence changes influence dynamic conformational changes during cotranscriptional folding. Here we investigated this question through the study of transcriptional fluoride riboswitches, non-coding RNAs that sense the fluoride anion through the coordinated folding and rearrangement of a pseudoknotted aptamer domain and a downstream intrinsic terminator expression platform. Using a combination of Escherichia coli RNA polymerase in vitro transcription and cellular gene expression assays, we characterized the function of mesophilic and thermophilic fluoride riboswitch variants. We showed that only variants containing the mesophilic pseudoknot function at 37°C. We next systematically varied the pseudoknot sequence and found that a single wobble base pair is critical for function. Characterizing thermophilic variants at 65°C through Thermus aquaticus RNA polymerase in vitro transcription showed the importance of this wobble pair for function even at elevated temperatures. Finally, we performed all-atom molecular dynamics simulations which supported the experimental findings, visualized the RNA structure switching process, and provided insight into the important role of magnesium ions. Together these studies provide deeper insights into the role of riboswitch sequence in influencing folding and function that will be important for understanding of RNA-based gene regulation and for synthetic biology applications.