Metallomics最新文献

Brassica cultivars have the ability to hyperaccumulate thallium when growing on soils contaminated with this element. Earlier research identified the presence of crystalline thallium deposits in the leaves of Brassica oleracea var. acephala. The aim of this study was to investigate the nature of these thallium crystals. A combination of synchrotron-based methods was used involving micro-X-ray fluorescence (µXRF) for the elemental distribution in the leaves and micro-X-ray diffraction mapping (µXDM) for the identification of the crystals. Thallium concentrates along the foliar margins, especially near vascular bundles, and dense congregations of minute thallium-rich crystals are observed in these areas. The thallium speciation is revealed to be nearly exclusively monovalent thallium, whilst the crystals are largely cubic thallium chloride, TlCl(s). The formation of thallium-rich crystals in the form of thallium chloride appears to be a tolerance mechanism similar to that of halophytes, and possibly a way in which excess thallium is expelled from leaves.

Metal ions play key roles in both physiological and pathological processes. The activity of nearly all nucleases depends on metal ions as cofactors. CRISPR-Cas system is widely used in gene editing and nucleic acid detection, and its ongoing development and frontier research have attracted significant attention. This study aims to explore and elucidate the effects of various metal ions on Cas12a-catalysed cleavage reactions including their specificity and regulatory mechanisms. Here, we found that certain metal ions significantly affected both the cleavage activity and the reaction specificity of Cas12a. Metal ions mediate enzyme-substrate binding by increasing the affinity between Cas12a and single-stranded DNA (ssDNA). In particular, unlike other metal ions, Mn2+ can achieve cleavage of ssDNA by only activating the catalytic domain without requiring the entire Cas12a. Structural alignment and site-directed mutagenesis of the active site revealed the structural basis of Cas12a catalysis and elucidated how metal ions influence its catalytic reaction in terms of specificity and regulatory mechanism. These results provide a theoretical foundation and offer innovative perspectives for the application of Cas12a-based enzyme technology.

THGP [3-(trihydroxygermyl) propanoic acid], an organogermanium compound, has been confirmed to exert multifaceted effects in mammalian and eukaryotic cells. Focusing on the characteristic trihydroxyl germanium moiety of THGP, we aimed to discover its novel pharmacological abilities and effects against multidrug-resistant Acinetobacter baumannii, a prokaryote with critical implications on global public health. In all assays, spectrometric determinations (OD) were conducted using a 96-well microtiter plate: OD489 for β-lactamase activity, OD600 for bacterial mass, OD570 for biofilm mass, OD340 for alcohol dehydrogenase (ADH) activity, and OD460 for dehydrogenases-NAD(P)-NAD(P)H system activity. THGP was observed to exhibit β-lactamase activity inhibition ability, which actually presents synergistic effects with cephem antibiotics against A. baumannii. We also revealed ADH activity inhibition ability, which contributes to the antiproliferative effect of THGP, a weak organic acid, against A. baumannii. However, low permeability of THGP through the bacterial cell because of its high hydrophilicity seemed to attenuate this intracellular effect. Furthermore, THGP was postulated to possess preventive effects on biofilm formation at sub-MIC (below the minimum inhibitory concentration) via an unknown mechanism. To our knowledge, this study is the first to report the antimicrobial effects of an organogermanium compound and demonstrates the inhibition abilities of THGP against two ubiquitous enzymes in pathogenic bacteria. However, the findings of this study are insufficient for clinical applications. Further studies are warranted to promote the development of clinically useful organogermanium compounds. Nevertheless, our findings provide important baseline information for future exploratory studies.

Phosphorus (P) is central to biology, yet it remains unclear whether P limitation acts as an isolated nutrient constraint or as a perturbation to a dynamical elemental network. We tested this using the rainbow trout liver cell line RTL-W1 by manipulating phosphorus supply (0%, 10%, and 100% of normal supply; P0, P10, and P100) and quantifying proliferation, protein content, metabolic activity, membrane integrity, and multielement composition. Phosphorus supply significantly altered cell proliferation and protein accumulation, with higher P supporting greater growth. Metabolic activity was affected by P supply, whereas membrane integrity remained largely stable, indicating altered allocation rather than generalized cellular damage. Compositional ionomic analysis revealed that phosphorus perturbation restructured the multielement network. At Day 3, treatment effects were strongest for P, K, and S. By Day 6, additional elements, including Sr and Mn, exhibited coordinated shifts relative to the P100 reference. Compositional data analysis showed that elemental imbalances shifted through time, consistent with flux rebalancing in an open system rather than static homeostasis. If phosphorus limitation were mechanistically independent, multielement composition would remain stable aside from P itself. Instead, phosphorus perturbation induced coordinated shifts across the ionome, consistent with rebalancing in open material systems.

Isotopes of calcium (Ca) in blood and urine have been introduced as a potential clinical tool for monitoring bone mineral balance (BMB). While several works support the ability of Ca isotope composition (δ44/42Ca) to capture a shift in BMB in response to external forcings (e.g. bed rest) or disease (e.g. osteoporosis), the influence of an individual's demographic, health status, diet or lifestyle on δ44/42CaUrine/Blood remains largely unconstrained. To gauge the effects of several variables among these four broader categories, we present a population study of δ44/42CaUrine from 103 individuals (age 18-76). Age is negatively correlated with δ44/42CaUrine, and we identify three other attributes (active vitamin D deficiency, vegetarian diet, and being post-menopausal) that lead to systematic differences in an individual's δ44/42CaUrine. Fluctuations in Ca reabsorption generate significant intra-individual δ44/42CaUrine variability. Within a typical range of reabsorption rates, however, the initial isotope composition (δ44/42CaSerum) exerts the strongest control on inter-individual δ44/42CaUrine variability. Using a simple Rayleigh model to express isotopic fractionation associated with Ca reabsorption in the kidneys, we find that a fractionation factor of 0.99972 reproduces the range of isotope ratios and excretion values for several, healthy individuals across three different studies and nearly a 30-year age span. Importantly, δ44/42CaUrine variations in three post-menopausal women from three separate studies cannot be explained by the same model, pointing to a different mechanistic control of δ44/42CaUrine in these subjects.

Zinc is an essential trace element, yet how graded dietary zinc intake reshapes tissue-specific distributions of zinc and other essential metals remains incompletely understood. This study investigated the impact of dietary zinc ranging from deficiency to high supplementation on the metallomic profile of C57BL/6 J mice. Mice were fed one of five zinc diets for 3 or 6 weeks, after which zinc status and related elements (copper, iron, manganese, calcium, and magnesium) were quantified in serum and multiple tissues by inductively coupled plasma-optical emission spectrometry, alongside expression of zinc transporter and metal-related genes in intestinal segments. Tissue zinc responses differed strongly across organs. Serum zinc increased only after prolonged supplementation, the colon and small intestine showed rapid and pronounced shifts with both deficiency and excess, brain and skeletal muscle regions displayed selective sensitivity, and liver and kidney zinc remained comparatively stable, consistent with strong homeostatic control. Dietary zinc did not deplete tissue copper but instead showed positive associations between zinc and copper in several tissues. We also observed co-ordinated and tissue-dependent relationships between zinc and iron, manganese, calcium, and magnesium, which challenges the traditional view that mineral interactions are uniformly antagonistic. When we integrated elemental and gene expression data and explicitly linked metal responses to measured tissue zinc levels, we identified segment-specific and transporter-specific adaptations that support a model in which dietary zinc reorganizes local and systemic mineral balance. This reorganization reflects both changes in tissue zinc levels and additional regulatory mechanisms in metal transport and storage that are not apparent from whole-tissue zinc measurements alone.

Understanding how chalcogen elements taken up by biological systems change their chemical speciation is essential for elucidating their intracellular behaviour. However, knowledge of the uptake and transformation of selenium and tellurium oxyanions in unicellular algae remains limited. In this study, selenium and tellurium oxyanions in different oxidation states (VI or IV) were added to two unicellular algae, Chlamydomonas reinhardtii and Pseudococcomyxa simplex, and their intracellular accumulation and chemical speciation were systematically investigated. X-ray absorption fine structure analysis revealed that both selenium and tellurium underwent intracellular reduction irrespective of their initial oxidation states. However, the extent of reduction, accumulation efficiency, and final chemical speciation differed markedly depending on both the oxidation state of the added oxyanion and the algal species, indicating shared yet species-dependent intracellular transformation patterns. In particular, tetravalent oxyanions (selenite and tellurite) underwent more rapid reduction and exhibited higher cellular accumulation than the corresponding hexavalent species in both algae, although the extent and kinetics of reduction differed markedly between species. Scanning and transmission electron microscopy demonstrated that selenium was immobilized as spherical elemental nanoparticles, whereas tellurium formed needle-like metallic nanorods within algal cells. Under hexavalent selenate exposure, higher-valent and organoselenium species remained detectable, and the formation of elemental selenium nanoparticles was limited. These results demonstrated speciation- and species-dependent intracellular transformation and accumulation of selenium and tellurium in unicellular algae, providing chemical speciation-based insights into algal chalcogen metabolism and detoxification processes.

Chromatin remodeling by SWI/SNF complexes is essential for transcriptional regulation, yet how distinct SWI/SNF subcomplexes contribute to cellular stress responses remains incompletely understood. Here, we identify a specific role for the PBAF subunit Baf180 in regulating metal-responsive transcription and adaptation to metal stress in proliferating myoblasts. While knockdown (KD) of the BAF-specific subunit Baf250a or the ncBAF-specific subunit Brd9 significantly impairs myoblast proliferation, KD of the PBAF-specific subunit Baf180 has no effect under basal conditions. Notably, supplementation with copper (Cu) or zinc (Zn) restores proliferative capacity in Baf250a- and Brd9-deficient myoblasts. In contrast, Baf180-depleted myoblasts exhibit impaired proliferation upon metal exposure, accompanied by selective dysregulation of genes involved in Cu and Zn homeostasis. Transcriptomic and chromatin profiling further reveal that loss of Baf180 alters the activity of metal-regulatory transcription factor 1 (MTF1), including reduced chromatin occupancy at metal-responsive loci. Together, these findings support a model in which PBAF promotes metal-responsive gene regulation to maintain metal homeostasis and sustain myoblast proliferation, uncovering a previously unrecognized link between nucleosome remodeling and metal homeostasis during muscle cell proliferation.

In recent years, in addition to their potential diagnostic and therapeutic properties, the immunogenic cell death (ICD) induction activity of iridium(III) and rhenium(I) complexes has been extensively reported. 4-Phenylimidazole (4-PIM), as an indoleamine 2,3-dioxygenase (IDO) inhibitor, can improve the immunosuppressive environment and enhance the efficacy of chemotherapy drugs. In this study, a series of Ir(III)/Re(I)-PIM complexes [Ir-PIM-(1-3) and Re-PIM-(1-3)] by coordination 4-PIM with iridium(III)/rhenium(I) metal centers were designed and synthesized to study their antitumor mechanisms. Among the six complexes screened, four compounds Ir-PIM-(1-3) and Re-PIM-1 showed good antitumor activity against human triple negative breast cancer (MDA-MB-231) cells. And Ir-PIM-(1-3)/Re-PIM-1 exhibited potential IDO inhibitory activity, which can suppress the expression of IDO protein. Further mechanistic studies indicate that Ir-PIM-(1-3)/Re-PIM-1 can effectively enter MDA-MB-231 cells, and induce the depolarization of mitochondrial membrane potential, the elevation of reactive oxygen species, G2/M phase cell cycle arrest and the release of damage-related molecular patterns, exhibiting dual activity in inducing both apoptosis and ICD.

Chronic exposure to copper ions, Cu(II), induces organ-specific oxidative damage and mitochondrial dysfunction, with distinct temporal and biochemical profiles across tissues. This study evaluated the protective effects of vitamin E (α-tocopherol) against Cu(II)-induced phospholipid and protein oxidation, redox imbalance, and bioenergetic disruption in rats. Cu(II) treatment led to early lipid peroxidation in the brain, heart, and lung, followed by delayed oxidative damage in the liver and kidney. Vitamin E effectively prevented phospholipid oxidation in all organs, but its protection against protein oxidation and mitochondrial respiratory impairment was organ-specific and time-dependent. Mitochondrial respiration declined in brain and heart tissues, with partial recovery in the heart after prolonged vitamin E supplementation. Electron transport chain activity was altered by Cu(II), notably with increased complex I activity in the liver and decreased complex I and II activity in the lung and kidney. Vitamin E failed to prevent these changes in most tissues. Glutathione modulation revealed adaptive redox responses in the lung and oxidative depletion in kidney. These findings highlight the complexity of Cu(II)-induced oxidative damage and the limited but significant protective role of vitamin E, emphasizing the need for targeted antioxidant strategies to preserve mitochondrial integrity and cellular function under metal-induced stress.