Zinc and manganese homeostasis closely interact in mammalian cells.

Understanding the homeostatic interactions among essential trace metals is important for explaining their roles in cellular systems. Recent studies in vertebrates suggest that cellular Mn metabolism is related to Zn metabolism in multifarious cellular processes. However, the underlying mechanism remains unclear. In this study, we examined the changes in the expression of proteins involved in cellular Zn and/or Mn homeostatic control and measured the Mn as well as Zn contents and Zn enzyme activities to elucidate the effects of Mn and Zn homeostasis on each other. Mn treatment decreased the expression of the Zn homeostatic proteins metallothionein (MT) and ZNT1 and reduced Zn enzyme activities, which were attributed to the decreased Zn content. Moreover, loss of Mn efflux transport protein decreased MT and ZNT1 expression and Zn enzyme activity without changing extracellular Mn content. This reduction was not observed when supplementing with the same Cu concentrations and in cells lacking Cu efflux proteins. Furthermore, cellular Zn homeostasis was oppositely regulated in cells expressing Zn and Mn importer ZIP8, depending on whether Zn or Mn concentration was elevated in the extracellular milieu. Our results provide novel insights into the intricate interactions between Mn and Zn homeostasis in mammalian cells and facilitate our understanding of the physiopathology of Mn, which may lead to the development of treatment strategies for Mn-related diseases in the future.

Assessment of radio-activation using spectroscopy in medical linear accelerators.

In radiotherapy, when photon energy exceeding 8 MV is utilized, photoneutrons can activate the components within the gantry of the linear accelerator (linac). At the end of the linac's lifecycle, radiation workers are tasked with its dismantling and disposal, potentially exposing them to unintentional radiation. This study aims to identify and measure the radioisotopes generated by this activation through spectroscopy, and to evaluate the effective dose rate. We selected nine medical linacs, considering various factors such as manufacturer (Siemens, Varian, and Elekta), model, energy, period of operation, and workload. We identified the radionuclides in the linac head by employing an in situ high-purity germanium (HPGe) detector. Spectroscopy and dose-rate measurements were conducted post-shutdown. We also measured the dose rates at the beam-exit window following irradiation with 10 MV and 15 MV photon beams. As a result of the spectroscopy, we identified approximately 20 nuclides including those with half-lives of 100 days or longer, such as 54Mn, 60Co, 65Zn, 122Sb, and 198Au. The dose rate measurements after 10 MV irradiation decreased to the background level in 10 min. By contrast, on 15 MV irradiation, the dose rate was 628 nSv/h after 10 min and decreased to 268 nSv/h after 1.5 hours. It was confirmed that the difference in the level of radiation and the type of nuclide depends on the period of use, energy, and workload. However, the type of nuclide does not differ significantly between the linacs. It is necessary to propose appropriate guidelines for the safety of workers, and disposal/move-install should be planned while taking into consideration the equipment's energy usage rate.

The Influence of Copper and Zinc on Photosynthesis and Phenolic Levels in Basil (Ocimum basilicum L.), Borage (Borago officinalis L.), Common Nettle (Urtica dioica L.) and Peppermint (Mentha piperita L.).

This work is aimed at relationships which govern zinc and copper uptake by four popular medicinal herbs: basil (Ocimum basilicum L.), borage (Borago officinalis L.), common nettle (Urtica dioica L.) and peppermint (Mentha piperita L.). They are often grown in soils with significant copper or zinc levels. Herbs were cultivated by a pot method in controlled conditions. Manganese, iron, copper and zinc concentrations were determined by High-Resolution Continuum Source Flame Atomic Absorption Spectrometry. The efficiency of photosynthesis was estimated by measuring the chlorophyll content, water use efficiency, net photosynthesis, intercellular CO2, stomatal conductance, and transpiration rate. Phenolic compounds were determined by the Folin-Ciocalteu method. Analysis of variance showed that herbs grown in soil treated with copper exhibited a lower iron content in roots, while manganese behaved in the opposite way. The only exception was borage, where a decrease in the manganese content in roots was observed. Both copper and zinc supplementations increased the total content of phenolics, while the highest increases were observed for common nettle and basil. Peppermint and borage responded less to supplementation. In the majority of samples, zinc and copper did not significantly affect the photosynthesis. Herbal extracts from common nettle and basil had unique antioxidant properties and may be good free radical scavengers.

Association between Multiple Trace Elements, Executive Function, and Cognitive Impairment with No Dementia in Older Adults.

Many studies suggest a significant association between individual essential trace elements (ETEs) and cognitive impairment in older adults, but evidence of the synchronized effect of multiple ETEs on cognitive function is lacking. We investigated the association between multiple ETEs, cognitive impairment with no dementia (CIND), and executive function in older Korean adults, using the Bayesian kernel machine regression (BKMR) model. Three hundred and thirty-six older adults were included as the study population and classified as the CIND and control groups. Blood manganese (Mn), copper (Cu), zinc (Zn), selenium (Se), and molybdenum (Mo) were measured as relevant ETEs. The frontal/executive tests included digit symbol coding (DSC), the Korean color word Stroop test (K-CWST), a controlled oral word association test (COWAT), and a trial-making test (TMT). Overall, the BKMR showed a negative association between multiple ETEs and the odds of CIND. Mn was designated as the most dominant element associated with the CIND (PIP = 0.6184), with a U-shaped relationship. Cu and Se levels were positively associated with the K-CWST percentiles (ß = 31.78; 95% CI: 13.51, 50.06) and DSC percentiles (ß = 25.10; 95% CI: 7.66, 42.53), respectively. Our results suggest that exposure to multiple ETEs may be linked to a protective mechanism against cognitive impairment in older adults.

Mesoporous cobalt-manganese layered double hydroxides promote the activation of calcium sulfite for degradation and detoxification of metronidazole.

Metronidazole (MNZ), a commonly used antibiotic, poses risks to water bodies and human health due to its potential carcinogenic, mutagenic, and genotoxic effects. In this study, mesoporous cobalt-manganese layered double hydroxides (CoxMny-LDH) with abundant oxygen vacancies (Ov) were successfully synthesized using the co-precipitation method and used to activate calcium sulfite (CaSO3) with slight soluble in water for MNZ degradation. The characterization results revealed that Co2Mn-LDH had higher specific areas and exhibited good crystallinity. Co2Mn-LDH/CaSO3 exhibited the best catalytic performance under optimal conditions, achieving a remarkable MNZ degradation efficiency of up to 98.1 % in only 8 min. Quenching experiments and electron paramagnetic resonance (EPR) tests showed that SO4•- and 1O2 played pivotal roles in the MNZ degradation process by activated CaSO3, while the redox cycles of Co2+/Co3+ and Mn3+/Mn4+ on the catalyst surface accelerated electron transfer, promoting radical generation. Three MNZ degradation routes were put forward based on the density functional theory (DFT) and liquid chromatography-mass spectrometer (LC-MS) analysis. Meanwhile, the toxicity analysis result demonstrated that the toxicity of intermediates post-catalytic reaction was decreased. Furthermore, the Co2Mn-LDH/CaSO3 system displayed excellent stability, reusability, and anti-interference capability, and achieved a comparably high removal efficiency across various organic pollutant water bodies. This study provides valuable insights into the development and optimization of effective heterogeneous catalysts for treating antibiotic-contaminated wastewater.

A cross-sectional analysis of the PURE study on minerals intake among Malaysian adult population with hypertension.

Hypertension (HPT) is the leading modifiable risk factor for cardiovascular diseases and premature death worldwide. Currently, attention is given to various dietary approaches with a special focus on the role of micronutrient intake in the regulation of blood pressure. This study aims to measure the dietary intake of selected minerals among Malaysian adults and its association with HPT. This cross-sectional study involved 10,031 participants from the Prospective Urban and Rural Epidemiological study conducted in Malaysia. Participants were grouped into HPT if they reported having been diagnosed with high blood pressure [average systolic blood pressure (SBP)/average diastolic blood pressure (DBP) ≥ 140/90 mm Hg]. A validated food frequency questionnaire (FFQ) was used to measure participants' habitual dietary intake. The dietary mineral intake of calcium, copper, iron, magnesium, manganese, phosphorus, potassium, sodium, and zinc was measured. The chi-square test was used to assess differences in socio-demographic factors between HPT and non-HPT groups, while the Mann-Whitney U test was used to assess differences in dietary mineral intake between the groups. The participants' average dietary intake of calcium, copper, iron, magnesium, manganese, phosphorus, potassium, selenium, sodium, and zinc was 591.0 mg/day, 3.8 mg/day, 27.1 mg/day, 32.4 mg/day, 0.4 mg/day, 1431.1 mg/day, 2.3 g/day, 27.1 µg/day, 4526.7 mg/day and 1.5 mg/day, respectively. The intake was significantly lower among those with HPT than those without HPT except for calcium and manganese. Continuous education and intervention should be focused on decreasing sodium intake and increasing potassium, magnesium, manganese, zinc, and calcium intake for the general Malaysian population, particularly for the HPT patients.

Independent Mutation of Two Bridging Carboxylate Ligands Stabilizes Alternate Conformers of the Photosynthetic O2-Evolving Mn4CaO5 Cluster in Photosystem II.

The O2-evolving Mn4CaO5 cluster in photosystem II is ligated by six carboxylate residues. One of these is D170 of the D1 subunit. This carboxylate bridges between one Mn ion (Mn4) and the Ca ion. A second carboxylate ligand is D342 of the D1 subunit. This carboxylate bridges between two Mn ions (Mn1 and Mn2). D170 and D342 are located on opposite sides of the Mn4CaO5 cluster. Recently, it was shown that the D170E mutation perturbs both the intricate networks of H-bonds that surround the Mn4CaO5 cluster and the equilibrium between different conformers of the cluster in two of its lower oxidation states, S1 and S2, while still supporting O2 evolution at approximately 50% the rate of the wild type. In this study, we show that the D342E mutation produces much the same alterations to the cluster's FTIR and EPR spectra as D170E, while still supporting O2 evolution at approximately 20% the rate of the wild type. Furthermore, the double mutation, D170E + D342E, behaves similarly to the two single mutations. We conclude that D342E alters the equilibrium between different conformers of the cluster in its S1 and S2 states in the same manner as D170E and perturbs the H-bond networks in a similar fashion. This is the second identification of a Mn4CaO5 metal ligand whose mutation influences the equilibrium between the different conformers of the S1 and S2 states without eliminating O2 evolution. This finding has implications for our understanding of the mechanism of O2 formation in terms of catalytically active/inactive conformations of the Mn4CaO5 cluster in its lower oxidation states.

Temperature-resilient and sustainable Mn-MOF oxidase-like nanozyme (UoZ-4) for total antioxidant capacity sensing in some citrus fruits: Breaking the temperature barrier.

Current nanozyme applications rely heavily on peroxidase-like nanozymes and are limited to a specific temperature range, despite notable advancements in nanozyme development. In this work, we designed novel Mn-based metal organic frameworks (UoZ-4), with excellent oxidase mimic activity towards common substrates. UoZ-4 showed excellent oxidase-like activity (with Km 0.072 mM) in a wide range of temperature, from 10 °C to 100 °C with almost no activity loss, making it a very strong candidate for psychrophilic and thermophilic applications. Ascorbic acid, cysteine, and glutathione could quench the appearance of the blue color of oxTMB, led us to design a visual-based sensing platform for detection of total antioxidant capacity (TAC) in cold, mild and hot conditions. The visual mode successfully assessed TAC in citrus fruits with satisfactory recovery and precisions. Cold/hot adapted and magnetic property will broaden the horizon of nanozyme applications and breaks the notion of the temperature limitation of enzymes.

Manganese-Doped Potassium Chloride Nanoelectrodes to Potentiate Electrochemical Immunotherapy.

Hypochlorous acid (HClO), as a powerful oxidizer, is obtained from the oxidation of Cl- ions during the electrochemical therapy (EChT) process for cancer therapy. However, the extracellular generated HClO is inadequate to inhibit effective tumor cell death. Herein, manganese-doped potassium chloride nanocubes (MPC NCs) fabricated and modified with amphipathic polymer PEG (PMPC NCs) to function as massive three-dimensional nanoelectrodes (NEs) were developed to enhance the generation of HClO for electrochemical immunotherapy under an alternating electric field. Under an square-wave alternating current (AC) electric field, the generation of HClO was boosted by PMPC NEs due to the enlarged active surface area, enhanced mass transfer rate, and improved electrocatalytic activity. Notably, PMPC NEs upregulated the intracellular HClO concentration to induce robust immunogenic cell death (ICD) under an AC electric field. Meanwhile, the electric-triggered release of Mn2+ effectively stimulated dendritic cells (DCs) maturation. In vivo results illustrated that PMPC-mediated EChT inhibited tumor growth and triggered the promotion of the immune response to regulate the tumor immune microenvironment. Based on the potent antitumor immunity, PMPC-mediated EChT was further combined with an immune checkpoint inhibitor (αCTLA-4) to realize combined EChT-immunotherapy, which demonstrated enhanced tumor inhibition of the primary tumors and an abscopal effect on distant tumors. To summarize, our work highlights the application of electrochemical-immunotherapy technology in tumor therapy.

A genome-wide association study provides insights into the genetic etiology of 57 essential and non-essential trace elements in humans.

Trace elements are important for human health but may exert toxic or adverse effects. Mechanisms of uptake, distribution, metabolism, and excretion are partly under genetic control but have not yet been extensively mapped. Here we report a comprehensive multi-element genome-wide association study of 57 essential and non-essential trace elements. We perform genome-wide association meta-analyses of 14 trace elements in up to 6564 Scandinavian whole blood samples, and genome-wide association studies of 43 trace elements in up to 2819 samples measured only in the Trøndelag Health Study (HUNT). We identify 11 novel genetic loci associated with blood concentrations of arsenic, cadmium, manganese, selenium, and zinc in genome-wide association meta-analyses. In HUNT, several genome-wide significant loci are also indicated for other trace elements. Using two-sample Mendelian randomization, we find several indications of weak to moderate effects on health outcomes, the most precise being a weak harmful effect of increased zinc on prostate cancer. However, independent validation is needed. Our current understanding of trace element-associated genetic variants may help establish consequences of trace elements on human health.

Association of serum five heavy metals level with all-cause and cause-specific mortality: a large population-based cohort study.

The study aimed to explore the association between five heavy metals exposure (Cadmium, Lead, Mercury, Manganese, and Selenium) and mortality [all-cause, cardiovascular disease (CVD), and cancer-related]. We integrated the data into the National Health and Nutrition Examination Survey from 2011 to 2018 years. A total of 16,092 participants were recruited. The link between heavy metals exposure and mortality was analyzed by constructing a restricted cubic spline (RCS) curve, Cox proportional hazard regression model, and subgroup analysis. The RCS curve was used to show a positive linear relationship between Cadmium, Lead, and all-cause mortality. In contrast, there was a negative linear correlation between Mercury and all-cause mortality. Additionally, Manganese and Selenium also had a J-shaped and L-shaped link with all-cause mortality. The positive linear, positive linear, negative liner, J-shaped, and L-shaped relationships were observed for Cadmium, Lead, Mercury, Manganese, and Selenium and CVD mortality, respectively. Cadmium, Lead, Mercury, and Selenium were observed to exhibit positive linear, U-shaped, negative linear, and L-shaped relationships with cancer-related mortality, respectively. There was an increase and then a decrease in the link between Manganese and cancer-related morality. This study revealed the correlation between the content of different elements and different types of mortality in the U.S. general population.

Innovative porous mortar filters: wastewater purification for clean water.

Water scarcity is a major global challenge that affects both developed and developing countries, with Indonesia serving as a prime example. Indonesia's archipelagic nature, combined with its dense population, exacerbates the severity of water scarcity. The increased population density in these areas raises the demand for water resources, putting a strain on the available supply. The purpose of this research was to create porous mortar filters (PMFs) with different ratios (1:4, 1:5, and 1:6) by incorporating 10, 15, and 20% adsorbent material by weight of fine aggregate. The research was carried out in three stages: determining PMF properties, preparing synthetic wastewater, and assessing treatment effectiveness. Various PMF compositions consistently achieved notable success, with reductions in total dissolved solids and turbidity exceeding 25 and 75%, respectively. The PMF performed admirably in eliminating bacterial concentrations, achieving a 100% removal rate, and was critical in efficiently reducing metals, with compositions achieving over 80% reduction for manganese (Mn) and 38% reduction for iron (Fe). PMF emerges as a practical solution as a cost-effective and simple water treatment technology, particularly suitable for areas with limited technological infrastructure and resources, providing accessible water treatment for communities facing challenges in this regard.

Manganese reductive dissolution coupled to Sb mobilization in contaminated shooting range soil.

A "redox-stat" RMnR bioreactor was employed to simulate moderately reducing conditions (+ 420 mV) in Sb-contaminated shooting range soils for approximately 3 months, thermodynamically favoring Mn(IV) reduction. The impact of moderately reducing conditions on elemental mobilization (Mn, Sb, Fe) and speciation [Sb(III) versus Sb(V); Fe2+/Fe3+] was compared to a control bioreactor RCTRL without a fixed redox potential. In both bioreactors, reducing conditions were accompanied by an increase in effluent Sb(V) and Mn(II) concentrations, suggesting that Sb(V) was released through microbial reduction of Mn oxyhydroxide minerals. This was underlined by multiple linear regression analysis showing a significant (p < 0.05) relationship between Mn and Sb effluent concentrations. Mn concentration was the sole variable exhibiting a statistically significant effect on Sb in RMnR, while under the more reducing conditions in RCTRL, pH and redox potential were also significant. Analysis of the bacterial community composition revealed an increase in the genera Azoarcus, Flavisolibacter, Luteimonas, and Mesorhizobium concerning the initial soil, some of which are possible key players in the process of Sb mobilization. The overall amount of Sb released in the RMnR (10.40%) was virtually the same as in the RCTRL (10.37%), which underlines a subordinate role of anoxic processes, such as Fe-reductive dissolution, in Sb mobilization. This research underscores the central role of relatively low concentrations of Mn oxyhydroxides in influencing the fate of trace elements. Our study also demonstrates that bioreactors operated as redox-stats represent versatile tools that allow quantifying the contribution of specific mechanisms determining the fate of trace elements in contaminated soils. KEY POINTS: • "Redox-stat" reactors elucidate Sb mobilization mechanisms • Mn oxyhydroxides microbial reductive dissolution has a major role in Sb mobilization in soils under moderately reducing conditions • Despite aging the soil exhibited significant Sb mobilization potential, emphasizing persistent environmental effects.

[Transcriptional analysis of the molecular response of Arabidopsis to manganese stress and recovery].

Manganese (Mn) is an essential element for plants and plays a role in various metabolic processes. However, excess manganese can be toxic to plants. This study aimed to analyze the changes in various physiological activities and the transcriptome of Arabidopsis under different treatments: 1 mmol/L MnCl2 treatment for 1 day or 3 days, and 1 day of recovery on MS medium after 3 days of MnCl2 treatment. During the recovery phase, minor yellowing symptoms appeared on the leaves of Arabidopsis, and the content of chlorophyll and carotenoid decreased significantly, but the content of malondialdehyde and soluble sugar increased rapidly. Transcriptome sequencing data shows that the expression patterns of differentially expressed genes exhibit three major models: initial response model, later response model, recovery response model. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis identified several affected metabolic pathways, including plant hormone signal transduction mitosolysis activates protein kinase (MAPK) phytohormone signaling, phenylpropanoid biosynthesis, ATP binding cassette transporters (ABC transporter), and glycosphingolipid biosynthesis. Differential expressed genes (DEGs) involved in phenylpropanoid biosynthesis, ABC transporter, and glycosphingolipid biosynthesis, were identified. Sixteen randomly selected DEGs were validated through qRT-PCR and showed consistent results with RNA-seq data. Our findings suggest that the phenylpropanoid metabolic pathway is activated to scavenge reactive oxygen species, the regulation of ABC transporter improves Mn transport, and the adjustment of cell membrane lipid composition occurs through glycerophospholipid metabolism to adapt to Mn stress in plants. This study provides new insights into the molecular response of plants to Mn stress and recovery, as well as theoretical cues for cultivating Mn-resistant plant varieties.

Multifunctional Manganese-Nucleotide Laccase-Mimicking Nanozyme for Degradation of Organic Pollutants and Visual Assay of Epinephrine via Smartphone.

As a natural green catalyst, laccase has extensive application in the fields of environmental monitoring and pollutant degradation. However, susceptibility to environmental influences and poor reusability seriously hinder its application. To address these concerns, for the first time, manganese ion replaced copper ion as the active center to coordinate with guanosine monophosphate (GMP) for synthesizing mimic laccase with high catalytic activity. Compared with natural laccase, the laccase-like nanozyme (Mn-GMPNS) demonstrated superior thermal stability, acid-base resistance, salt tolerance, reusability, and substrate universality. Benefiting from the high catalytic activity of Mn-GMPNS, epinephrine, a significant neurotransmitter and hormone associated with numerous diseases, was visually detected within 10 min and a portable assay by smartphone. More encouragingly, Mn-GMPNS can efficiently degrade dye pollutants, achieving a decolorization rate over 70% within 30 min. Thus, the coordination between manganese ion and nucleotide demonstrated the potential in rational design of nanozymes with high catalytic activity, low cost, good stability, and good biocompatibility.

Predicting Redox Conditions in Groundwater at a National Scale Using Random Forest Classification.

Redox conditions in groundwater may markedly affect the fate and transport of nutrients, volatile organic compounds, and trace metals, with significant implications for human health. While many local assessments of redox conditions have been made, the spatial variability of redox reaction rates makes the determination of redox conditions at regional or national scales problematic. In this study, redox conditions in groundwater were predicted for the contiguous United States using random forest classification by relating measured water quality data from over 30,000 wells to natural and anthropogenic factors. The model correctly predicted the oxic/suboxic classification for 78 and 79% of the samples in the out-of-bag and hold-out data sets, respectively. Variables describing geology, hydrology, soil properties, and hydrologic position were among the most important factors affecting the likelihood of oxic conditions in groundwater. Important model variables tended to relate to aquifer recharge, groundwater travel time, or prevalence of electron donors, which are key drivers of redox conditions in groundwater. Partial dependence plots suggested that the likelihood of oxic conditions in groundwater decreased sharply as streams were approached and gradually as the depth below the water table increased. The probability of oxic groundwater increased as base flow index values increased, likely due to the prevalence of well-drained soils and geologic materials in high base flow index areas. The likelihood of oxic conditions increased as topographic wetness index (TWI) values decreased. High topographic wetness index values occur in areas with a propensity for standing water and overland flow, conditions that limit the delivery of dissolved oxygen to groundwater by recharge; higher TWI values also tend to occur in discharge areas, which may contain groundwater with long travel times. A second model was developed to predict the probability of elevated manganese (Mn) concentrations in groundwater (i.e., ≥50 µg/L). The Mn model relied on many of the same variables as the oxic/suboxic model and may be used to identify areas where Mn-reducing conditions occur and where there is an increased risk to domestic water supplies due to high Mn concentrations. Model predictions of redox conditions in groundwater produced in this study may help identify regions of the country with elevated groundwater vulnerability and stream vulnerability to groundwater-derived contaminants.

Catalytic oxidation of toluene by manganese oxides: Effect of K+ doping on oxygen vacancy.

Alkali metal potassium was beneficial to the electronic regulation and structural stability of transition metal oxides. Herein, K ions were introduced into manganese oxides by different methods to improve the degradation efficiency of toluene. The results of activity experiments indicated that KMnO4-HT (HT: Hydrothermal method) exhibited outstanding low-temperature catalytic activity, and 90% conversion of toluene can be achieved at 243°C, which was 41°C and 43°C lower than that of KNO3-HT and Mn-HT, respectively. The largest specific surface area was observed on KMnO4-HT, facilitating the adsorption of toluene. The formation of cryptomelane structure over KMnO4-HT could contribute to higher content of Mn3+ and lattice oxygen (Olatt), excellent low-temperature reducibility, and high oxygen mobility, which could increase the catalytic performance. Furthermore, two distinct degradation pathways were inferred. Pathway Ⅰ (KMnO4-HT): toluene → benzyl → benzoic acid → carbonate → CO2 and H2O; Pathway ⅠⅠ (Mn-HT): toluene → benzyl alcohol → benzoic acid → phenol → maleic anhydride → CO2 and H2O. Fewer intermediates were detected on KMnO4-HT, indicating its stronger oxidation capacity of toluene, which was originated from the doping of K+ and the interaction between KOMn. More intermediates were observed on Mn-HT, which can be attributed to the weaker oxidation ability of pure Mn. The results indicated that the doping of K+ can improve the catalytic oxidation capacity of toluene, resulting in promoted degradation of intermediates during the oxidation of toluene.

An exploratory study on the association of multiple metals in serum with preeclampsia.

Background: Individual metal levels are potential risk factors for the development of preeclampsia (PE). However, understanding of relationship between multiple metals and PE remains elusive. Purpose: The purpose of this study was to explore whether eight metals [zinc (Zn), manganese (Mn), copper (Cu), nickel (Ni), lead (Pb), arsenic (As), cadmium (Cd), and mercury (Hg)] in serum had a certain relationship with PE. Methods: A study was conducted in Dongguan, China. The concentrations of metals in maternal serum were assessed using inductively coupled plasma mass spectrometry (ICP-MS). Data on various factors were collected through a face-to-face interview and hospital electronic medical records. The unconditional logistic regression model, principal component analysis (PCA) and Bayesian Kernel Machine Regression (BKMR) were applied in our study. Results: The logistic regression model revealed that the elevated levels of Cu, Pb, and Hg were associated with an increased risk of PE. According to PCA, principal component 1 (PC1) was predominated by Hg, Pb, Mn, Ni, Cu, and As, and PC1 was associated with an increased risk of PE, while PC2 was predominated by Cd and Zn. The results of BKMR indicated a significant positive cumulative effect of serum metals on PE risk, with Ni and Cu exhibiting a significant positive effect. Moreover, BKMR results also revealed the nonlinear effects of Ni and Cd. Conclusion: The investigation suggests a potential positive cumulative impact of serum metals on the occurrence of PE, with a particular emphasis on Cu as a potential risk factor for the onset and exacerbation of PE. These findings offer valuable insights for guiding future studies on this concern.

Lipophilic Group-Modified Manganese(II)-Based Contrast Agents for Vascular and Hepatobiliary Magnetic Resonance Imaging.

Effective vascular and hepatic enhancement and better safety are the key drivers for exploring gadolinium-free hepatobiliary contrast agents. Herein, a facile strategy proposes that the high lipophilicity may be favorable to enhancing sequentially vascular and hepatobiliary signal intensity based on the structure-activity relationship that both hepatic uptake and interaction with serum albumins partly depend on lipophilicity. Therefore, 11 newly synthesized derivatives of manganese o-phenylenediamine-N,N,N',N'-tetraacetic acid (MnLs) were evaluated as vascular and hepatobiliary agents. The maximum signal intensities of the heart, liver, and kidneys were strongly correlated with log P, a key indicator of lipophilicity. The most lipophilic agent, MnL6, showed favorable relaxivity when binding with serum albumin, good vascular enhancement, rapid excretion, and reliable hepatobiliary phases comparable to a classic hepatobiliary agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for in vivo liver tumor imaging. Inhibition experiments confirmed the hepatic targeting of MnL6 is mediated by organic anion-transporting polypeptides.

Joint and interactive effects of metal mixtures on liver damage: Epidemiological evidence from repeated-measures study.

BACKGROUND: The impact of heavy metals on liver function has been examined in numerous epidemiological studies. However, these findings lack consistency and longitudinal validation. METHODS: In this study, we conducted three follow-up surveys with 426 participants from Northeast China. Blood and urine samples were collected, along with questionnaire information. Urine samples were analyzed for concentrations of four metals (chromium [Cr], cadmium [Cd], lead [Pb], and manganese [Mn]), while blood samples were used to measure five liver function indicators (alanine aminotransferase [ALT], aspartate aminotransferase [AST], albumin [ALB], globulin [GLB], and total protein [TP]). We utilized a linear mixed-effects model (LME) to explore the association between individual heavy metal exposure and liver function. Joint effects of metal mixtures were investigated using quantile g-computation and Bayesian kernel machine regression (BKMR). Furthermore, we employed BKMR and Marginal Effect models to examine the interaction effects between metals on liver function. RESULTS: The LME results demonstrated a significant association between urinary heavy metals (Cr, Cd, Pb, and Mn) and liver function markers. BKMR results indicated positive associations between heavy metal mixtures and ALT, AST, and GLB, and negative associations with ALB and TP, which were consistent with the g-comp results. Synergistic effects were observed between Cd-Cr on ALT, Mn-Cr and Cr-Pb on ALB, while an antagonistic effect was found between Mn-Pb and Mn-Cd on ALB. Additionally, synergistic effects were observed between Mn-Cr on GLB and Cd-Cr on TP. Furthermore, a three-way antagonistic effect of Mn-Pb-Cr on ALB was identified. CONCLUSION: Exposure to heavy metals (Cr, Cd, Mn, Pb) is associated with liver function markers, potentially leading to liver damage. Moreover, there are joint and interaction effects among these metals, which warrant further investigation at both the population and mechanistic levels.