The magnesium ion is one of the divalent cations that have an important role in chromosome condensation. Research about the role of Mg2 + has been conducted on the chromosomes from various types of cells, especially human cancer cell lines. Nonetheless, no research has been conducted on normal human cells, such as blood cells and lymphocytes. Therefore, a study to evaluate the effect of Mg2+ on chromosome structure in normal cells is required. This study aims to assess the effects of Mg2+ on chromosome structure in lymphocytes using GTL-banding and karyotyping. Metaphase chromosomes were obtained by culturing blood cells, followed by banding using Giemsa and Leishman stain. Mg2+ role was assessed using XBE5 solution (5 mM Mg2+) as control, XBE solution (0 mM Mg2+), and 1 mM EDTA solution as a cation chelator. The chromosome value from each treatment was evaluated using Quality Assessment from the Association for Clinical Cytogenetics according to the International System for Human Cytogenomics Nomenclature (ISCN). The result shows that the control chromosome had a compact structure with a clear banding pattern and bold band intensity, while those treated with XBE and EDTA had a less compact and fibrous structure with an unclear banding pattern and thin band intensity. In addition, the average chromosome score±SD of the XBE (4.389 ± 0.607) and EDTA-treated (4.611 ± 0.607) chromosomes were higher than those of the control (4.222 ± 0.427). These data indicated that Mg2+ is essential in maintaining the structure of the human lymphocyte chromosome.

To investigate the molecular mechanisms by which magnesium (Mg)-based implants, specifically Mg-containing intramedullary nails (Mg-IMNs), promote femoral fracture healing.

Rats with femoral fractures were treated with Mg-IMNs. In vitro experiments were conducted to assess the impact of Mg2+ on osteoclastogenesis and histone lactylation. Histological analysis, Western blotting, and qRT-PCR were employed to evaluate osteoclast maturation and the molecular pathways involved. In vivo, lactate was administered to replicate Mg-IMN effects, and lactate production was inhibited to observe potential reversal effects.

Mg-IMNs significantly enhanced fracture healing by inhibiting osteoclastogenesis. Mg2+ promoted intracellular lactate production, leading to histone lactylation, which suppressed osteoclast maturation by downregulating NFATc1. The P300/H3K18LA/HDAC1 pathway was identified as a key mediator in this process. Additionally, lactate administration mimicked the effects of Mg-IMNs, while blocking lactate reversed these effects.

This study uncovers a novel mechanism by which Mg2+ promotes fracture healing through histone lactylation-mediated inhibition of osteoclastogenesis. These findings offer new therapeutic strategies for enhancing fracture repair via epigenetic regulation.

Magnesium (Mg) and its alloys are receiving increasing attention in peripheral nerve regeneration, but they were limited due to the low corrosion resistance and rapid degradation. In this study, GDNF-Gel/HA-Mg was prepared and its value in peripheral nerve defects repairment was explored both in vitro and in vivo.

A hydroxyapatite (HA) coating was first applied to the pure Mg surface, followed by the formation of gelatin methacrylate (GelMA) loaded with glial cell-derived neurotrophic factor (GDNF) on the HA-coated Mg surface. GDNF-Gel/HA-Mg corrosion resistance was explored. The effect of GDNF-Gel/HA-Mg conduit on Schwann cell proliferation and migration abilities were investigated. And sciatic nerve defects models were established to explored the role of GDNF-Gel/HA-Mg conduit in peripheral nerve defects repairment.

The electrochemical, immersion, and hydrogen evolution experiments indicated that the corrosion resistance in phosphate buffer saline (PBS) of pure Mg was significantly improved by the GDNF-Gel/HA coating. Cell cycle, Cell Count Kit-8 (CCK-8), and clone formation assays indicated that GDNF-Gel/HA-Mg promoted the proliferation of Schwann cells. Scratch and Transwell assay results demonstrated that GDNF-Gel/HA-Mg promoted Schwann cell migration ability dose-dependently. GDNF-Gel/HA-Mg was found to enhance the secretion of nerve growth factor (NGF) and the expression of p75NTR. Flow cytometry results showed that GDNF-Gel/HA-Mg could reduce H2O2-induced oxidative stress and Schwann cell apoptosis. GDNF-Gel/HA-Mg inhibited M1 macrophage polarization while facilitated M2 macrophage polarization in a concentration-dependent manner. The in vivo studies demonstrated that GDNF-Gel/HA-Mg conduit could significantly promote the regeneration and myelination of sciatic nerve, as well as the recovery of denervated gastrocnemius atrophy.

The GDNF-Gel/HA-Mg conduit prepared in this study exhibited good hydrophilicity and corrosion resistance and greatly enhanced the proliferation, migration, and invasion abilities of Schwann cells, as well as peripheral nerve regeneration.

Four major regions (Birjand, Zirkoh, Darmian, and Qaen) of barberry cultivation in South Khorasan, Iran, were selected and investigated. According to the findings, the most abundant mineral elements in the barberry fruits were on average in the order of potassium > phosphorus > calcium > iron > magnesium. The greatest amounts of potassium and calcium were detected in the samples from the Zirkoh region, and the greatest amounts of phosphorus and iron were detected in the samples from the Qaen region. The amounts of zinc and copper in the Birjand, Zirkoh, and Darmian regions were recorded within the allowed range. Heavy elements arsenic and mercury were not present in the samples from all four regions. However, among the studied areas, the Birjand area had the lowest amount of lead and cadmium. According to food standards (FAO and WHO), lead concentration was to some extent greater than maximum level.

To analyse the prevalence of magnesium disturbances in children admitted to the Paediatric Intensive Care Unit (PICU) and its relationship with complications and mortality. Single-center, observational, retrospective study. Children with measured serum magnesium levels were included. Clinical, analytical, treatment data, clinical severity scores (Functional Status Scale, Paediatric Risk of Mortality, Paediatric Logistic Organ Dysfunction and Paediatric Multiple Organ Dysfunction Score) at admission and during PICU admission, mortality and duration of admission were recorded. A cohort of 200 children (57% male) with a median age of 55 months (interquartile range 8 months to 11 years) were included. Six children (3%) presented initial hypomagnesemia and 26 (13%) presented hypomagnesemia during admission. Hypomagnesemia during admission was significantly associated with the presence of acute kidney injury (AKI) (p = 0.038), shock (p = 0.003), and extracorporeal membrane oxygenation (ECMO) (p = 0.046). Patients with hypomagnesemia had a higher mortality (15.4% versus 1.7%) (p = 0.006). 64 children (32%) presented initial hypermagnesemia, and 89 (44.5%) presented hypermagnesemia during admission. Hypermagnesemia during admission was significantly associated with heart surgery (p < 0.001), without significant differences in mortality (p = 0.702). Hypomagnesemia and hypermagnesemia are common among children admitted to the PICU. Hypomagnesemia during admission was associated with AKI, shock, ECMO and mortality. Hypermagnesemia during admission was associated with cardiac surgery but not with mortality.

To investigate whether granuloma formation following self-administered cosmetic oil injections affects mineral homeostasis, specifically calcium, magnesium, phosphate, iron, sodium, and potassium, and to assess the potential impact of prednisolone treatment on these mineral levels.

In this retrospective study, we reviewed blood samples from baseline through a follow-up period of 48 months in patients referred to a tertiary center at Herlev Hospital, Denmark. Changes in serum minerals over time were assessed by a linear mixed model for repeated measures.

A total of 111 patients were included. Men who injected > 2,000 mL paraffin oil had higher total and ionized calcium (p = 0.029 and p < 0.001), lower PTH (p < 0.001), but also lower magnesium (p < 0.001) and higher sodium (p = 0.048) compared to those who had injected < 500 mL. Men with manifest hypercalcemia at baseline (n = 32) compared to men with normocalcemia (n = 79) experienced an increase in serum PTH and phosphate concentrations over time (p = 0.042 at 48 months), and also a transient increase in iron concentration, although this reached baseline levels again after 24 months. Prednisolone lowered calcium in hypercalcemic men but also decreased serum magnesium (p = 0.027 after 36 months), phosphate, and increased serum iron concentration.

Men who had injected large volumes of paraffin oil were more likely to have hypercalcemia, lower magnesium, and higher sodium concentrations. Minor aberration in serum minerals was more frequent in patients with more pronounced disease and this may likely be a poor prognostic sign although the mechanism behind this observation remains unclear.

This cross-sectional study aimed to investigate the correlation between magnesium consumption and periodontitis in different body mass index (BMI) and waist circumference (WC) groups. 8385 adults who participated in the National Health and Nutrition Examination Survey during 2009-2014 were included. The correlation between dietary magnesium intake and periodontitis was first tested for statistical significance by descriptive statistics and weighted binary logistic regression. Subgroup analysis and interaction tests were performed to investigate whether the association was stable in different BMI and WC groups. There was a statistical difference in magnesium intake between periodontitis and non-periodontitis populations. In model 3, participants with the highest magnesium consumption had an odds ratio of 0.72 (0.57-0.92) for periodontitis compared to those with the lowest magnesium consumption. However, in subgroup analysis, the relationship between magnesium intake and periodontitis remained significant only in the non-general obese (BMI ≤ 30 kg/m2) and non-abdominal obese populations (WC ≤ 102 cm in men and ≤ 88 cm in women). Dietary magnesium intake might decrease the periodontitis prevalence in the American population, and this beneficial periodontal health role of magnesium consumption might only be evident in non-general obese and non-abdominal obese populations.

Infected wounds present a significant clinical challenge, exacerbated by antibiotic resistance, which complicates effective treatment. This study introduces a hydrogel (CC/AP@CM) embedded with core-shell bioactive glass nanoparticles designed for the controlled, sequential release of copper (Cu2+) and magnesium (Mg2+) ions. The hydrogel is crosslinked via a Schiff base reaction, endowing it with injectable, self-healing, and adhesive properties. Notably, the bilayer structure of the bioactive glass within the hydrogel allows an initial release of Cu2+ ions to trigger an early-stage pro-inflammatory and antimicrobial response, followed by Mg2+ ions that support tissue repair and an anti-inflammatory environment. This design aligns with natural wound healing stages, promoting a shift in macrophage polarization from the M1 to M2 phenotype, effectively balancing antibacterial defense with tissue regeneration. The hydrogel demonstrated robust antibacterial efficacy against MRSA, increased angiogenesis, and enhanced fibroblast proliferation and migration in vitro. In a murine wound model, it significantly accelerated wound closure and immune activation, including responses from dendritic cells and T cells. These findings suggest that this hydrogel, through its stage-specific immunomodulatory properties and temporally controlled ion release, offers a promising strategy for treating complex wound infections, supporting both immune defense and tissue healing.

Achillea L., a medicinal plant belonging to the Asteraceae family, has a global distribution and has been employed for its therapeutic properties since ancient times. Different species within the Achillea genus are frequently employed to tackle various health concerns. While there has been considerable research conducted on the bioactive compounds found in these plants and their corresponding biological activities, there remains a notable gap in our understanding of their mineral composition. Therefore, the present study aimed to systematically evaluate the mineral profile within and across three Achillea species, namely A. vermicularis, A. wilhelmsii, and A. tenuifolia. The study focused on the analysis of eight minerals, namely Fe, Cd, K, Ca, Pb, Mg, Cu, and P, over a span of two crop years.

Based on the results, the mineral composition varied significantly among the species and accessions. In the study, the K (3.9-4.48%) content in all three examined species was found to be abundant. Comparatively, the Fe content in the A. wilhelmsii (952 mg/kg) and A. vermicularis (1047 mg/kg) species was more than double that of the A. tenuifolia (390 mg/kg) species. The Cu content, on the other hand, demonstrated similar levels across all three species. The highest concentrations of Mg (0.59%), Ca (1.79%), and P (0.62%) were observed in A. wilhelmsii, A. tenuifolia, and A. vermicularis species, respectively. Notably, A. tenuifolia species exhibited the lowest level of Pb, while the A. vermicularis species had the lowest level of Cd. In the studied plants, the minerals were found to have the following concentration order: K > Ca > P > Mg > Fe > Cu > Pb > Cd. The cluster analysis categorized the 25 accessions into three distinct groups, revealing no similarity among accessions within each species. The PCA plot, utilizing the first two PC, validated approximately 46% of the total variance. This confirmation solidified the outcomes derived from the cluster analysis.

In conclusion, this study provides valuable insights into the mineral composition of Achillea species, highlighting the variability among species and accessions. The findings contribute to our understanding of the nutritional and therapeutic potential of these plants and can guide future research on their cultivation and utilization in various applications.

Currently, there are more significant threats to food security compared to earlier decades because of the accelerating rate of climate change [...].

Enset is a multipurpose perennial root crop primarily used as a staple food for over 25 million people in Ethiopia. Despite the existence of various landraces, little information is known about their nutritional profile. Thus, the aim of this study was to determine the nutritional and anti-nutritional contents of qocho from the eight widely cultivated landraces. Traditionally fermented qocho samples were milled individually into a fine powder and analyzed by applying standard food procedures. The mean proximate component (%) varied in moisture value from 59.0-66.5, crude protein (1.75-3.15), crude fat (0.14-0.73), crude fiber (2.25-5.39), and total ash (1.2-2.4), whereas the total carbohydrates came to 89.74-94.64, and gross energy was 370.69-387.97 kcal/100 g. The mean contents of minerals (mg/100 g) ranged: calcium (80.17-110.60), potassium (90.35-157.14), magnesium (14.37-16.35), phosphorus (10.84-40.19), sodium (7.41-8.35), iron (4.08-6.71), and zinc (0.39-0.73) on a dry weight basis. The mean anti-nutritional values (mg/100 g) for oxalate, tannin, and phytate ranged from 6.26-9.39, 5.04-32.05, and 74.28-141.19, respectively. This showed that the qocho samples contain low contents of anti-nutritional factors. Regarding molar ratios, phytate to calcium, phytate × calcium to zinc, and oxalate to calcium were shown below the critical values. Overall, the qocho of the analyzed enset landraces had a considerable variation in nutritional profile. Therefore, continued identification is crucial to distinguish the enset landraces with more nutritious qocho for local and regional consumption as well as to sustain enset cultivation for food security.

Hereditary hypomagnesemia with secondary hypocalcemia (HSH) is a rare autosomal recessive disorder caused by biallelic variants in the transient receptor potential melastatin 6 (TRPM6) gene, typically presenting in infancy. Currently, there is a lack of reports in the literature on adult-onset cases. This case report describes a 51-year-old male with adult-onset HSH, presenting with limb weakness, muscle spasms, and electrolyte imbalances, including severe hypomagnesemia (0.28 mmol/L). Genetic testing revealed a novel heterozygous variant in the TRPM6 gene (c.4914del, p.E1638Dfs*8), classified as likely pathogenic. The patient's symptoms significantly improved following magnesium supplementation, and his electrolyte levels gradually normalized. This case highlights the importance of considering HSH in patients with unexplained hypomagnesemia and emphasizes the role of genetic testing in confirming the diagnosis. The findings also suggest that magnesium supplementation can effectively alleviate symptoms and improve the quality of life in patients with adult-onset HSH. Early recognition and treatment are crucial to prevent potential complications, such as neurological damage.

In recent years, increasing evidence has shown that metals play important roles in both innate and adaptive immunity. An emerging concept of metalloimmunotherapy has been proposed, which may accelerate the development of immunotherapy for cancers. Here, we discuss how metals affect T cell function through different signaling pathways. Metals impact the fate of T cells, including their activation, proliferation, cytotoxicity, and differentiation. Most importantly, metals also participate in mitochondrial operation by regulating energy production and reactive oxygen species homeostasis in T cells. We also identified the metal-based mutual effects between tumor cells and T cells in the tumor microenvironment. Overall, the antitumor effect of T cells can be improved by targeting metal metabolism and metalloimmunotherapy, which will be a step forward in the treatment of cancers.

Escherichia coli (E.coli) is the leading pathogen for deaths associated with antimicrobial resistance, making it the most problematic bacteria for human infections. This study aimed to investigate the association between serum magnesium levels and clinical outcomes in patients with E.coli sepsis.

Data of E.coli septic patients were collected from the MIMIC-IV database. Patients were divided into three groups based on tertiles of serum magnesium levels. Three models were utilized, including the raw model (unadjusted), Model I (adjusted for age and gender), and Model II (adjusted for all potential confounding factors). Linear model and two-segment nonlinear model were established to examine the relationship between serum magnesium and 30-day, 60-day, and 90-day mortality rates. Kaplan-Meier survival curve analysis was performed to assess cumulative hazard of mortalities at 30-day, 60-day, 90-day based on tertiles of serum magnesium levels.

A total of 421 E.coli septic patients were included and classified into tertiles: Q1(< 1.6 mg/dL), Q2 (1.6-1.9 mg/dL), Q3(> 1.9 mg/dL). In the Model adjusting for all potential confounders, for every 1 mg/dL increase in serum magnesium, there was a significant increase in 30-day, 60-day, and 90-day mortality rates, with odds ratios of 4.01 (95% CI 1.22-13.19, P = 0.022), 4.81 (95% CI 1.59-14.53, P = 0.005), and 4.45 (95% CI 1.52-12.96, P = 0.006) respectively. And linear model is more suitable for describing the relationship between serum magnesium levels and clinical outcomes. Kaplan-Meier analysis revealed that the cumulative hazard of mortalities at 30-day, 60-day, 90-day increased with the prolongation of hospital stay, particularly in the group with the highest serum magnesium level.

Increased level of serum magnesium is significantly associated with increased risk of 30-day, 60-day and 90-day mortality in a population of septic patients with E.coli infection.

Magnesium is a vital mineral with a crucial role in different biochemical reactions. There is a contradicting evidences about its role in maintaining bone, muscle and cardiovascular health. Recently, magnesium supplements gained attention due to claimed effectiveness in improving sleep quality and relieving muscle spasm.

This study aimed to assess Arab communities' knowledge, attitudes and practices regarding magnesium supplementation.

A cross-sectional self-administered survey was disseminated to collect responses from different Arab countries. Descriptive statistics were calculated for demographics. Data normality was assessed using Shapiro-Wilk test. Associations between sociodemographic variables and knowledge, attitudes and practices were explored using simple and multiple linear regression. Significance level was considered at p < 0.05.

A total of 1,445 responses were collected. Mean (±SD) knowledge scores were low 8.61 ± 5.9. Eighty seven percent recognized magnesium role in alleviating muscle spasm and sleep disorders (83%). Magnesium citrate was the mostly used magnesium salt (37.43%). Neutral attitudes were observed with a mean score of 3.02 ± 0.66. Only 31.8% reported using magnesium supplements, 36.1% of them received a medical consultation. Having poly cystic ovary (p = 0.033), relying on scientific articles (0.004), receiving pharmacist consultation (p = 0.019) significantly associated with higher knowledge.

Despite the huge debate regarding magnesium benefits in maintaining muscle, bone health and improving sleep quality, this study found that there is a significant gap in knowledge and neutral attitude towards magnesium supplementation in Arab communities. These findings emphasizes the need for educational campaigns targeting the public on the rationale use of supplements.

The prognostic value of Magnesium Depletion Score (MDS) in Diabetic Kidney Disease (DKD) patients is still unclear. This study aimed to determine the associations between MDS and long-term mortality in DKD population.

Data were obtained from the National Health and Nutrition Examination Survey (NHANES III). MDS is calculated from four specific scoring items: estimated glomerular filtration rate (eGFR), heavy drinking, use of proton pump inhibitors (PPI), and use of diuretics. Multivariate Cox proportional hazards regression models was employed to explore the association between MDS and all-cause and cause specific mortality, with emphasis on age-specific analysis.Mediation analysis explored if metabolic indices mediate the relation between MDS and mortality. Sensitive analyses were performed to check the robustness of the main findings.

3,179 patients with DKD were included in this study, with 1,698 females and 1,481 males. The multivariate Cox regression analyses showed higher MDS were significantly associated with the all-cause mortality of DKD population [MDS ≥ 3: adjusted hazard ratio (HR):1.932, 95% confidence interval (CI): 1.339-2.787,p < 0.001]. Meanwhile, the trend was also significant in cardiovascular mortality of the DKD population (MDS ≥ 3: HR = 3.688, 95%CI: 1.702-8.577,p < 0.001). Heavy drinking was the most influential factor among the four MDS scoring items that affects mortality outcomes. Mediation analysis showed increased MDS could slightly improve metabolic levels, but the improvement was insufficient to reverse the mortality outcome in DKD patients. Subgroup analysis manifested that the result was more applicable for patients over 60. The result of the sensitive analysis confirmed the robustness of the main conclusion.

Our study highlights the clinical prognostic value of MDS in predicting the survival of the DKD population, especially among patients over 60. The findings imply that reducing alcohol consumption and performing routine cardiovascular health assessments for DKD patients with MDS > 2 are important for prolonging DKD patients' survival time.

Many abnormalities in laboratory tests have been described in severe coronavirus disease (COVID-19), but most of them probably just reflect the degree of organ dysfunction and are not true risk factors for death. The present study is a secondary analysis of a clinical trial carried out in patients hospitalized due to severe COVID-19 (ClinicalTrials.gov identifier No. NCT04443673). We explored the association of clinical laboratory tests and serum cytokines with death in COVID-19 patients, either considering only the initial measurement obtained shortly after the patient's arrival at the emergency room, or by means of the weighted average of all measurements during the entire hospitalization. The study included 56 patients with a mean age of 58.6 years (range from 31.8 to 86.2 years), with a fatality rate of 58.9% (33 patients). Among initial laboratory tests, only mean corpuscular volume (MCV), erythrocyte count, serum magnesium, and age showed a trend (p < 0.10, univariable logistic regression) for an association with a fatal outcome. However, in the multivariable logistic regression, only MCV and magnesium remained associated with death, with adjusted odds ratios (95% confidence intervals) of 1.253 (1.047-1.501, p = 0.014) and 0.091 (0.010-0.798, p = 0.03), respectively. Serum magnesium tended to decrease during the hospital stay in both groups, survivors and non-survivors. Compared with survivors, patients who died had a higher weighted average of urea, blood urea nitrogen (BUN), procalcitonin, MCV, neutrophils, neutrophil/lymphocyte ratio, fibrinogen/albumin ratio, C-reactive protein/albumin ratio, BUN/albumin ratio, IL-6, and IL-10, as well as decreased weighted average of albumin, lymphocytes, and monocytes, among others. In conclusion, patients with severe COVID-19 who had lower serum magnesium on their arrival at the emergency room were more prone to die. On the other hand, serum magnesium tended to decrease during the patients' hospital stay, independently of the outcome.Trial Registration: ClinicalTrials.gov NCT04443673.

The magnesium depletion score (MDS) is considered a new valuable predictor of body magnesium status. This study aimed to explore the association between MDS and PAD among participants aged ≥ 40 years on the National Health and Nutrition Examination Survey in 1999-2004. Survey-weighted multivariable logistic regression and restricted cubic spline models were used to assess the association between MDS and PAD. Survey-weighted multivariable logistic regression showed a significant positive association between MDS and the prevalence of PAD. For each unit increase in MDS, the risk of PAD increased by 24%. Compared to individuals with MDS = 0, those with MDS ≥ 3 had a 95% higher risk of PAD. Restricted triple spline analysis showed a linear dose-response relationship between MDS and PAD risk. Subgroup analysis indicated that this positive association was stronger in individuals aged > 60 years. Numerous future longitudinal cohort studies are required to validate our findings.

Muscle satellite cells (MuSCs) respond immediately to environmental cues upon skeletal muscle injuries. Despite decades of research into muscle regeneration, the specific molecular factors that trigger the transition of MuSCs from a quiescent to an active state remain largely unidentified. Here, we identify transient receptor potential melastatin 7 (TRPM7), an Mg2+-permeable ion channel, as a critical regulator of MuSC activation. Trpm7 deletion in MuSCs reduced Mg2+ influx, impairing myofiber regeneration and leading to decreased MuSC numbers and cell cycle arrest during regeneration. These changes were linked to disrupted mTOR signaling, which drives the transition of MuSCs from G0 to GAlert phase. In addition, Trpm7-deficient MuSCs exhibited impaired early responses, including quiescent projection retraction and AP-1 induction. Mg2+ supplementation rescued these defects, restoring normal MuSC activation. Our findings reveal a previously unrecognized mechanism where Mg2+ permeation through TRPM7 is essential for MuSC activation and efficient skeletal muscle regeneration, highlighting TRPM7 as a critical regulator of muscle repair.

Numerous studies have shown inverse associations between serum magnesium (Mg) and risk of cardiovascular disease (CVD), but studies of dietary Mg have not been consistent. To examine the association of a Mg-rich diet score with risks of CVD, coronary heart disease (CHD), and ischaemic stroke in the Atherosclerosis Risk in Communities (ARIC) study.

There were 15 022 Black and White adults without prevalent CVD at baseline (1987-89) included in this analysis. Diet was assessed at two visits 6 years apart using an interviewer-administered 66-item food frequency questionnaire. A Mg-rich diet score was created that included servings of whole grain products, nuts, vegetables, fruit, legumes, coffee, and tea. Cox proportional hazard regression evaluated associations of incident CVD, CHD, and stroke across quintiles of Mg-rich diet score, adjusting for demographics, lifestyle factors, and clinical characteristics. Over >30 years of follow-up, there were 3531 incident CVD events (2562 CHD, 1332 ischaemic stroke). Participants who consumed more Mg-rich foods were older, female, White, had lower blood pressure, fewer were not current smokers, and more reported being physically active. A Mg-rich diet was inversely associated with incident CVD (HRQ5 vs. Q1 = 0.87, 95% CI: 0.77-0.98, Ptrend = 0.02) and CHD (HRQ5 vs. Q1 = 0.82, 95% CI: 0.71-0.95, Ptrend = 0.01); however, the diet-stroke association was null (HRQ5 vs. Q1 = 1.00, 95% CI: 0.82-1.22, Ptrend = 0.97).

Consuming a diet including Mg-rich foods, such as whole grains, nuts, vegetables, fruits, legumes, coffee, and tea, is associated with lower risk of CVD and CHD, but not ischaemic stroke.

Drug-induced liver injury represents a critical public health issue, marked by unpredictable and potentially severe adverse reactions to medications, herbal products or dietary supplements.

Acetaminophen is notably a leading cause of hepatotoxicity, impacting over one million individuals worldwide.

Extensive research has elucidated the intricate mechanisms driving APAP-induced liver injury, emphasising the significant roles of endoplasmic reticulum stress, oxidative stress, mitochondrial dysfunction and cell death.

These insights pave the way for innovative therapeutic strategies, including the use of magnesium, bile acids, microbiota modulation and mesenchymal stem cells.

This review explores into these pathological mechanisms, proposing viable therapeutic interventions for patients suffering from APAP-induced liver injury.

Preeclampsia (PE) is a common pregnancy complication characterized by hypertension, proteinuria, and end-organ dysfunction. However, to date, no effective treatment has been established other than iatrogenic delivery, and the importance of prevention as an alternative approach to addressing PE has been emphasized. There is growing evidence on the effectiveness of pharmacological and non-pharmacological prophylaxis in preventing PE. In this review, we focused on dietary supplements as non-pharmacological prophylaxis for PE. Calcium is a well-documented supplement for the prevention of PE. Daily 500 mg calcium supplementation can roughly halve the risk of PE in settings where calcium intake is low, including in Japan. According to recent systematic reviews and network meta-analyses, current evidence on the efficacy of vitamin D supplementation is inconsistent. Although vitamin D is a candidate for the prevention of PE, future large-scale randomized control trials are necessary to draw definitive conclusions. We also reviewed other dietary supplements, including vitamins (vitamins A, B6, C, and E, folic acid, and multivitamins), minerals (magnesium, zinc, and iron), amino acids (l-arginine and l-carnitine), anti-oxidants (lycopene, resveratrol, and astaxanthin), and other agents (omega-3 fatty acids, coenzyme Q10, melatonin, and s-equol). In this study, we provide a comprehensive approach to help develop better preventive strategies and ultimately reduce the burden of PE.

This study aimed to investigate the potential association between magnesium depletion score (MDS), a novel assessment of magnesium status in vivo, and all-cause and cardiovascular mortality in asthma patients.

Using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018, 4757 asthmatics were included in the study and were categorized into four groups based on their MDS levels (MDS=0, MDS=1, MDS=2, and MDS≥3). Survival differences between the different MDS groups were analysed using Kaplan-Meier curves, and weighted multivariate Cox regression models assessed the relationship between MDS and mortality. In addition, non-linear relationships between MDS and all-cause and cardiovascular mortality were explored using restricted cubic spline (RCS) regression models, and subgroup analyses were performed to validate the results.

Kaplan-Meier curves showed that both all-cause and cardiovascular mortality were significantly higher in the group with higher levels of MDS (P < 0.001). After controlling for all confounders, asthmatics in the higher MDS group faced a higher risk of death compared with the lower MDS group, as evidenced by a 3.29-fold increase in all-cause mortality (95 % CI: 2.05, 5.29) and a 4.68-fold increase in cardiovascular mortality (95 % CI: 1.77, 12.35). Fully adjusted Cox regression models further confirmed the significant positive association of high MDS with the risk of all-cause and cardiovascular mortality.RCS plots revealed a linear dose-response relationship between MDS and mortality. In the subgroup analyses, no interaction factors other than cardiovascular disease were found to significantly influence the relationship between MDS and mortality.

Higher levels of MDS independently predicted the risk of mortality, especially cardiovascular mortality, in US adults with asthma. Therefore, the MDS may become a cost-effective and widely applicable prognostic assessment tool for asthma, providing an important reference for clinical decision-making and patient management.

Bio-based triboelectric nanogenerators (TENGs) are expected to power medical device and detect real-time human motion behavior due to eco-friendliness and biocompatibility. However, the output performance of the TENGs needs to be boosted. In this study, a biodegradable silk fibroin-based TENG with enhanced output performance regulated by interfacial and ionic polarization is proposed. The friction layers, regenerated silk fibroin (RSF) film and silk nanoribbon (SNR) film, are functionalized through the induction of histidine with imidazolyl and lithium chloride, respectively, thus increasing the dielectric constant and triboelectric properties of friction layers. The enhancement is attributed to the enlarged difference of electron-absorbing ability and electron-donating ability of the two friction layers. The total silk fibroin-based TENG shows a maximum voltage of 63.0 V, and a current of 2.4 μA. Moreover, the obtained maximum power density of 828.8 mW m-2 is 9.5 times higher than that of the counterpart without functionalization. And the output power density is much higher than that of existing fully degradable bio-based TENGs reported previously. The components of the silk fibroin-based TENG can gradually degrade in vitro. As a wearable device, the silk fibroin-based TENG can precisely monitor real-time human motion due to its high sensitivity, which can realize self-powered supply and simultaneous sensing. Moreover, the unencapsulated TENG is successfully used as a self-powered humidity sensor. The bio-based TENGs with enhanced performance highlight their application potential in wearable and implantable fields.

Tissue engineering aims to repair damaged tissues with physiological functions recovery. Although several therapeutic strategies are there for tissue regeneration, the functional recovery of regenerated tissues still poses significant challenges due to the lack of concerns of tissue innervation. Design rationale of multifunctional biomaterials with both tissue-induction and neural induction activities shows great potential for functional tissue regeneration. Recently, the research and application of inorganic biomaterials attracts increasing attention in innervated multi-tissue regeneration, such as central nerves, bone, and skin, because of its superior tunable chemical composition, topographical structures, and physiochemical properties. More importantly, inorganic biomaterials are easily combined with other organic materials, biological factors, and external stimuli to enhance their therapeutic effects. This review presents a comprehensive overview of recent advancements of inorganic biomaterials for innervated multi-tissue regeneration. It begins with introducing classification and properties of typical inorganic biomaterials and design rationale of inorganic-based material composites. Then, recent progresses of inorganic biomaterials in regenerating various nerves and nerve-innervated tissues with functional recovery are systematically reviewed. Finally, the existing challenges and future perspectives are proposed. This review may pave the way for the direction of inorganic biomaterials and offers a new strategy for tissue regeneration in combination of innervation.

Depression represents a significant global health burden, ranking as one of the leading causes of disability worldwide, and nutrition plays a key role in mental health. Vitamin A, essential for immune and neurological function, has shown conflicting associations with depression. Magnesium, essential for neurotransmission and neuroprotection, is associated with a reduced risk of depression. Importantly, magnesium is required for the activation of enzymes involved in vitamin A metabolism, suggesting a potential interaction between these nutrients in depression. However, this interaction remains poorly understood. This study investigates how magnesium intake modifies the relationship between vitamin A and depression, with the aim of elucidating their combined effects and informing personalized dietary strategies for depression prevention.

Data for this study were extracted from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2016, involving a total of 60,936 participants. The final analysis included 25,277 adults aged ≥20 years (Female: 12,581, Male:12,696), excluding pregnant women, individuals under 20, and those with incomplete data. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), supplemented by self-reporting questionnaires. Dietary intake was assessed via a recall interview at the mobile examination center (MEC). Dietary vitamin A intake, treated as a continuous variable, was categorized based on the median intake value. Stratified analyses were conducted based on sex and magnesium intake levels (Female: low: <310 mg/day; high: ≥310 mg/day; Male: low: <400 mg/day; high: ≥400 mg/day).

Our cross-sectional study showed that in women with low magnesium intake, higher vitamin A intake was associated with a reduced risk of depression (OR: 0.83, 95% CI: 0.76-0.92, p < 0.001), whereas no significant association was observed in the high magnesium group. Men did not show such an interaction. There was also a significant interaction between vitamin A levels and magnesium intake in reducing the incidence of depression (p-value for interaction = 0.145).

Our study suggests that a sex-specific interaction between dietary magnesium and vitamin A in modulating depression risk. This interaction highlights the potential role of combined nutritional interventions in depression management. Further randomized controlled trials are warranted to confirm these findings.

Hypomagnesemia early diagnosis and consequently early, timely magnesium supplementation is of utmost benefit, but it often goes underdiagnosed. The objective was to show and monitor an intervention to identify hypomagnesemia in patients with arrhythmia.

A cross-sectional study was designed in the laboratory. In primary care patients, the Laboratory Information System would automatically add a serum magnesium test when sample availability is present in any request when a diagnosis of arrhythmia is made. We counted the number of detected patients with hypomagnesemia (serum magnesium <1.7 mg/dL, <0.7 mmol/L), and calculated the cost in reagent of each identified case.

In 430 patients with arrhythmia, serum magnesium was measured, and 41 (9.5%) had hypomagnesemia results. One patient showed severe hypomagnesemia values (<1.2 mg/dL and <0.49 mmol/L). Patients with a deficit were significantly ( P <0.01) older than the total group of patients with normal magnesium values (66.3±13.2 versus 61.6±12.5). Each case represented a cost of 3.15€ in reagent.

The automated computer-based intervention to identify patients with hypomagnesemia was useful and affordable, given the cost per detected case.

Clear cell renal cell carcinoma (ccRCC) poses significant clinical challenges due to its high metastatic rate at diagnosis and resistance to conventional therapies. The magnesium transporter NIPAL4, involved in lipid metabolism and magnesium ion homeostasis, has recently been implicated in cancer biology but remains understudied in ccRCC. In this study, we identifies NIPAL4 as a potential prognostic marker and therapeutic target in ccRCC. High NIPAL4 expression is associated with poor prognosis and contributes to tumor proliferation and migration. Bioinformatics analyses indicate that NIPAL4 is involved in critical pathways related to the extracellular matrix, lipid metabolism, and the TGF-β signaling pathway. Moreover, NIPAL4's association with immune cell infiltration and immune checkpoint molecules highlights its potential as an immunotherapy marker. These findings warrant further investigation into NIPAL4's role in ccRCC to develop more effective treatment strategies.

Dietary factors are critical risk factors for cardiovascular diseases (CVD). Among various aspects of dietary intake, the dietary calcium-to-magnesium (Ca: Mg) ratio has been less studied. The present study aimed to evaluate the association of the dietary Ca: Mg ratio with 10-year cardiovascular risk among participants of the health cohort of medical staff in Shiraz, Iran. This cross-sectional study utilized baseline data from the Shiraz University of Medical Sciences Employees' Health Cohort Study (SUMS EHCS). Demographic, anthropometric, and laboratory data were collected. A 113-item food frequency questionnaire was used to assess dietary intake. The 10-year risk of developing cardiovascular disease (CVD) was estimated using the Framingham Risk Score. Linear regression modeling examined the association between the dietary Ca: Mg ratio and 10-year coronary risk. Of the SUMS EHCS participants, 3,382 subjects (1,515 males and 1,867 females) with a median (IQR) age of 41.00 (10.00) years were eligible for the study. In both univariate and adjusted models, a 1-unit increase in the Ca: Mg ratio was associated with higher levels of 10-year coronary risk: B = 0.097 (95% CI: 0.044, 0.150) in the univariate model and B = 0.091 (95% CI: 0.038, 0.143) in the adjusted model. The findings indicated that a higher dietary Ca: Mg ratio was associated with a higher 10-year risk of CVD.

Magnesium (Mg2+) is essential for cardiovascular and metabolic health, yet hypomagnesemia is common in kidney transplant recipients (KTRs) due to immunosuppressive therapy and renal dysfunction. Oral Mg2+ supplementation is often ineffective due to poor absorption and side effects. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to increase serum Mg2+ in chronic kidney disease, but their effects in KTRs, particularly patients without diabetes, remain unclear. This observational study assessed 63 KTRs treated with dapagliflozin, analyzing the serum Mg2+ levels at baseline and after 3 and 6 months. The hypomagnesemia prevalence, associations with oral supplementation, diabetes status, and diuretic use were evaluated. The results showed a significant Mg2+ increase with SGLT2i therapy, reducing hypomagnesemia regardless of the diabetes status. Oral supplementation did not correlate with improved Mg2+ levels, reinforcing its limited efficacy. Additional benefits included reductions in the body weight, blood pressure, and serum urate without compromising graft function. SGLT2i may offer a novel approach to managing hypomagnesemia in KTRs, potentially reducing the reliance on ineffective supplements while providing renal and cardiovascular benefits. Further research is needed to confirm these findings and elucidate the underlying mechanisms.

Background: Magnesium sulfate reduces opioid use and its associated side effects. However, no consensus exists on whether the optimal dosing should be based on actual body weight or adjusted ideal body weight. The primary objective of this study was to compare postoperative analgesia after magnesium sulfate infusion, using doses calculated based on actual body weight versus adjusted ideal body weight. Methods: This prospective, randomized, double-blind, controlled clinical trial included 75 participants who underwent target-controlled intravenous general anesthesia. The participants were divided into three groups: a control group (CG), a group receiving magnesium sulfate calculated by actual body weight (AWG), and a group receiving magnesium sulfate calculated based on the adjusted ideal body weight (IWG). Results: The AWG had significantly lower pain scores than the CG (p < 0.001) and IWG (p=0.017). Opioid use was similar between the AWG and IWG, but significantly higher in the CG (AWG = IWG, p=0.08; CG > AWG, p < 0.001; CG = IWG, p 0.03). The increase in magnesium concentration did not reach clinically relevant levels. Neuromuscular blockade latency decreased in the groups receiving magnesium sulfate (p < 0.001 in both comparisons) compared to the CG. Conclusion: Calculating the dose of magnesium sulfate based on actual body weight enhances postoperative analgesia. The increase in magnesium concentration was not clinically significant and did not interfere with the action of cisatracurium in the groups receiving magnesium sulfate. Trial Registration: ClinicalTrials.gov identifier: NCT04645719.

Both silicon (Si) and magnesium (Mg) ions play essential roles in bone health. However, the precise mechanisms by which these two ions enhance osteogenic differentiation remain to be fully elucidated. Herein, a Si-Mg dual-ion system was designed to investigate the effects of Si and Mg ions on the cytological behavior of mouse bone marrow mesenchymal stem cells (mBMSCs). The molecular mechanism of the Si-Mg dual-ion system regulating osteogenic differentiation of mBMSCs was investigated by transcriptome sequencing technology. In the single-ion system, the Si group with concentrations of 1.5 and 0.75 mM exhibited good combined effects (cell proliferation, alkaline phosphatase (ALP) activity, and osteogenic differentiation gene expression (Runx2, OPN, and Col-I)) of mBMSCs. The Mg group with concentrations of 5 and 2.5 mM showed better combined effects (cell proliferation, ALP activity, and osteogenic differentiation gene expression) of mBMSCs. In the dual-ion system, the silicon (0.75 mM)-magnesium (2.5 mM) experimental group significantly enhanced the proliferation, ALP activity, and osteogenesis-related gene expression (Runx2, OPN, and Col-I) of mBMSCs. The analysis of transcriptome sequencing results showed that Mg ions had a certain pro-stem cell osteogenic differentiation regulatory effect. Si ions had a stronger regulation on osteogenic differentiation than the Mg ions. The regulation of osteogenic differentiation by Si-Mg dual ions was synergistically enhanced compared to that of a single ion. In addition, the transforming growth factor beta (TGF-β) signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway were involved in mediating the pro-stem cell osteogenic differentiation by Si-Mg dual ions. This study sheds light on investigating the molecular mechanism of dual-ion regulation of the osteogenic differentiation of mBMSCs and enriches the theory of ion-regulating osteogenic differentiation.

Background/Objectives: Although the importance of magnesium for overall health and physiological function is well established, its influence on exercise performance is less clear. The primary study objective was to determine the influence of short-term magnesium supplementation on cycle ergometer exercise performance. The hypothesis was that magnesium would elicit an ergogenic effect. Methods: A randomized, double-blind, placebo-controlled, two-period crossover design was used to study men and women who were regular exercisers. Fifteen participants ingested either a placebo or magnesium chloride (MgCl2 300 mg) twice per day, for 9 days, separated by a 3-week washout. During days 8 and 9, participants completed a battery of cycle ergometer exercise tests, and whole blood, vastus lateralis, and stools were sampled. The primary outcomes were the maximal oxygen uptake (VO2max), a simulated 10 km time trial, and the sprint exercise performance. Additional outcomes included skeletal muscle mitochondrial respiration, and, on account of the known laxative effects of magnesium, the gut microbiota diversity. Results: Compared with a placebo, MgCl2 supplementation increased the circulating ionized Mg concentration (p < 0.03), decreased the VO2max (44.4 ± 7.7 vs. 41.3 ± 8.0 mL/kg/min; p = 0.005), and decreased the mean power output during a 30 s sprint (439 ± 88 vs. 415 ± 88 W; p = 0.03). The 10 km time trial was unaffected (1282 ± 126 vs. 1281 ± 97 s; p = 0.89). In skeletal muscle, MgCl2 decreased mitochondrial respiration in the presence of fatty acids at complex II (p = 0.04). There were no significant impacts on the gut microbiota richness (CHAO1; p = 0.68), Shannon's Diversity (p = 0.23), or the beta-diversity (Bray-Curtis distances; p = 0.74). Conclusions: In summary, magnesium supplementation had modest ergolytic effects on cycle ergometer exercise performance and mitochondrial respiration. We recommend that regular exercisers, free from hypomagnesemia, should not supplement their diet with magnesium.

Regenerating natural gradients of the tendon‒bone interface (TBI) is a major challenge in the reconstruction of rotator cuff tear (RCT). In this study, magnetic Janus hydrogel microrobots to match the TBI orientation during RCT reconstruction surgery are developed via a biofriendly gas-shearing microfluidic platform. Through separate loading of Mg2+ and Zn2+, the microrobots facilitate the immediate restoration and long-term maintenance of the natural mineral gradient in the TBI after implantation and alignment through magnetic manipulation. In vitro studies confirm the spatiotemporal cell phenotype modulation effects of the microrobots. In a rat RCT model, microrobots synchronously promote the bone and tendon regeneration, and the restoration of gradient tendon‒bone transition structures in the TBI. Overall, by rebuilding the Mg2+/Zn2+ mineral gradient, cell phenotype gradient and structural gradient of the TBI, magnetic Janus microrobots loaded with dual bioactive ions represent a promising strategy for promoting TBI healing in RCT reconstruction surgery.

Magnesium (Mg) is necessary for plants as a structural element or an enzyme cofactor. It also plays a significant role in the light and dark responses of photosynthesis. Moringa plants are considered one of the most important medicinal plants that humans need for nutrition. The aim of the study is to provide Mg to plants in an easy and simple way. Therefore, it is widely available in human food due to its nutritional importance. In this experiment, the treatment was done on the Moringa plant as, one of the medicinal plants that is increasingly used in fresh form. The experiment was conducted at the research farm of the National Research Center. Magnesium oxide has been extracted and prepared in a natural way that is safe for humans, plants, and soil. Trichoderma viride filtrate was used as a chelating agent in an environmentally friendly process to create magnesium oxide nanoparticle (MgO-NPs). FTIR, TEM, and SEM-EDX were utilized to analyze and characterize the synthesized. Plants were treated with different doses to determine the optimal concentration for the plant. The effect of treatment on plants was to improve vegetation such, as a number of leaves (232.15), leaf area (273.97 cm2), and fresh weight (3693.17 g). It also increased dry matter in the plant (171.8 g), chemical properties, and elements.

The CorA/Mrs2 family of pentameric proteins are cardinal for the influx of Mg2+ across cellular membranes, importing the cation to mitochondria in eukaryotes. Yet, the conducting and regulation mechanisms of permeation remain elusive, particularly for the eukaryotic Mrs2 members. Here, we report closed and open Mrs2 cryo-electron microscopy structures, accompanied by functional characterization. Mg2+ flux is permitted by a narrow pore, gated by methionine and arginine residues in the closed state. Transition between the conformations is orchestrated by two pairs of conserved sensor-serving Mg2+-binding sites in the mitochondrial matrix lumen, located in between monomers. At lower levels of Mg2+, these ions are stripped, permitting an alternative, symmetrical shape, maintained by the RDLR motif that replaces one of the sensor site pairs in the open conformation. Thus, our findings collectively establish the molecular basis for selective Mg2+ influx of Mrs2 and an auto-ligand-gating regulation mechanism.

Nanotechnology has been utilized in diverse domains, encompassing sustainable agriculture. However, the ecotoxicity and environmental safety of nanoparticles need to be evaluated before their large-scale use. This study synthesizes and characterizes magnesium (Mg) and zinc (Zn) co-doped aluminum (Al) oxide (MgZnAl2O4) NPs and elucidates its potential growth-promoting or genotoxic performance on barley (Hordeum vulgare L.). XRD, EDX, TEM, SEM, and XPS were used to characterize the MgZnAl2O4 NPs. After characterization, the seedlings were grown in a hydroponic solution containing 0, 50, 100, 200, and 400 mg L-1 NPs for 3 weeks. The germination, growth indices, photosynthetic parameters, and nutrient absorption properties were determined. Confocal microscopy, TEM, and SEM were utilized to follow the path and reveal the structural and morphological effects of NPs. The potential genotoxic effect was evaluated using the RAPD-PCR method. Elemental composition analysis of plant parts confirmed that synthesized MgZnAl2O4 NPs, sized at 21.8 nm, were up-taken by the plant roots, leading to increased Mg, Zn, and Al contents of leaves. In addition, compared with the untreated control, the abundance of Ca, K, B, Fe, Mn, and Cu were increased by the NPs treatment. In addition, physiological indices like germination rate (~ 11%), root and leaf growth (15-29%), chlorophyll, and carotenoids (~ 39%) pigments were significantly raised by the NPs inclusion. It can be concluded that low concentrations (< 200 mg L-1) of MgZnAl2O4 NPs enhance growth parameters effectively and are safe for plant growth. On the other hand, a phytotoxic and genotoxic impact was observed at high concentrations (100-400 mg L-1). However, considerable amounts of NPs were found to be adsorbed on roots, disrupting root morphology and cell membrane integrity, thus nutrient trafficking and transport. Therefore, it is recommended that MgZnAl2O4 NPs can be used in barley breeding programs at low concentrations. Adding micro- or macroelements required by plants to the NP composition is a promising way to compensate for plant nutrition. However, the negative effects of MgZnAl2O4 NPs on the environment and other living beings due to their genotoxic effects at high doses must be carefully considered.

Hypomagnesemia is a common electrolyte abnormality that can cause a wide range of neuromuscular symptoms, including muscle weakness, tremor, and tetany. However, it is a rare cause of isolated lower extremity weakness. We present a case of a 71-year-old female with multiple comorbidities who developed severe bilateral lower extremity weakness and upper extremity tremor in the setting of profound hypomagnesemia (serum magnesium level of 1.0 mg/dL) after an acute diarrheal illness. The patient's weakness and tremor rapidly improved with intravenous magnesium supplementation. This case highlights the importance of considering hypomagnesemia in the differential diagnosis of acute bilateral lower extremity weakness and the potential for rapid reversal with magnesium repletion.

The distal convoluted tubule (DCT) plays an indispensable role in magnesium (Mg2+) reabsorption in the kidney. Yet, the extrusion mechanism of Mg2+ has not been identified. The solute carrier 41A3 (SLC41A3) has been suggested to be involved in Mg2+ extrusion, but this has never been conclusively demonstrated.

Using available RNA-sequencing data and real-time quantitative PCR, expression of two alternative Slc41a3 transcripts, encoding isoform (Iso) 1 or 2, were assessed in kidney and isolated DCT tubules. HEK293 or HAP1 cells were transfected with plasmids expressing either of the isoforms, followed by 25Mg2+ transport studies. Identification of cis-regulatory elements (CRE) was achieved by combining data from publicly available ATAC sequencing data and luciferase assays.

Gene expression studies revealed a distinct transcript of Slc41a3 in the DCT with an alternative promoter, leading to a protein with a unique N-terminus; SLC41A3-Iso 2. HEK293 cells overexpressing SLC41A3-Iso 2, but not -Iso 1, exhibited 2.7-fold and 1.6-fold higher 25Mg2+ uptake and extrusion, compared to mock, respectively. The transport was independent of Na+, of the Mg2+ channel TRPM7 or of transporters CNNM3 and -4. We identified a CRE accessible in the DCT, ±2.8kb upstream of the transcript. The presence of the CRE increased the Slc41a3-Iso 2 promoter activity 3.8-fold following luciferase assays, indicating the CRE contains an enhancer function.

In conclusion, we identified two alternative transcripts of Slc41a3 in mouse. Slc41a3-Iso 2 is enriched within the DCT using specific gene regulatory elements. We speculate that specifically in the DCT, SLC41A3-Iso 2 orchestrates Mg2+ extrusion.