SEARCH · PubMed Health

Results for “Copper”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2023

The genetic basis of adaptation to copper pollution in Drosophila melanogaster.

Introduction: Heavy metal pollutants can have long lasting negative impacts on ecosystem health and can shape the evolution of species. The persistent and ubiquitous nature of heavy metal pollution provides an opportunity to characterize the genetic mechanisms that contribute to metal resistance in natural populations. Methods: We examined variation in resistance to copper, a common heavy metal contaminant, using wild collections of the model organism Drosophila melanogaster. Flies were collected from multiple sites that varied in copper contamination risk. We characterized phenotypic variation in copper resistance within and among populations using bulked segregant analysis to identify regions of the genome that contribute to copper resistance. Results and Discussion: Copper resistance varied among wild populations with a clear correspondence between resistance level and historical exposure to copper. We identified 288 SNPs distributed across the genome associated with copper resistance. Many SNPs had population-specific effects, but some had consistent effects on copper resistance in all populations. Significant SNPs map to several novel candidate genes involved in refolding disrupted proteins, energy production, and mitochondrial function. We also identified one SNP with consistent effects on copper resistance in all populations near CG11825, a gene involved in copper homeostasis and copper resistance. We compared the genetic signatures of copper resistance in the wild-derived populations to genetic control of copper resistance in the Drosophila Synthetic Population Resource (DSPR) and the Drosophila Genetic Reference Panel (DGRP), two copper-naïve laboratory populations. In addition to CG11825, which was identified as a candidate gene in the wild-derived populations and previously in the DSPR, there was modest overlap of copper-associated SNPs between the wild-derived populations and laboratory populations. Thirty-one SNPs associated with copper resistance in wild-derived populations fell within regions of the genome that were associated with copper resistance in the DSPR in a prior study. Collectively, our results demonstrate that the genetic control of copper resistance is highly polygenic, and that several loci can be clearly linked to genes involved in heavy metal toxicity response. The mixture of parallel and population-specific SNPs points to a complex interplay between genetic background and the selection regime that modifies the effects of genetic variation on copper resistance.

Drosophila↗

PubMed2026

Copper-Containing Surface Engineering for Soft-Tissue Biomedical Devices: Structure-Function Relationships and Ion Release-Driven Biological Performance, A Systematic Review.

Copper and copper-based materials have gained increasing attention for the functional modification of implantable medical devices intended for prolonged soft-tissue contact, including vascular stents, catheters, and intrauterine devices. Owing to their broad-spectrum antimicrobial activity, redox reactivity, and involvement in angiogenesis and cellular signaling, copper-based systems offer significant potential for multifunctional surface engineering. However, achieving a balance between antibacterial efficacy, corrosion behavior, controlled ion release, and cytocompatibility remains a critical challenge. This PRISMA-compliant systematic review analyzes copper-containing materials and surface modification strategies for soft-tissue biomedical applications. A structured search of Scopus, Web of Science, and PubMed (2015-2025) identified 65 eligible studies. The review encompasses bulk copper-containing alloys, electrochemical and chemical surface modification techniques, physical vapor deposition approaches, and advanced hybrid systems integrating copper with polymers, hydrogels, or metal-phenolic networks. Across the reviewed literature, antibacterial performance was strongly dependent on copper concentration, microstructural distribution, and spatiotemporal ion release profiles. Moderate, well-controlled copper incorporation frequently improved antibacterial efficacy while maintaining acceptable hemocompatibility and cytocompatibility, particularly in vascular and blood-contacting devices. In contrast, excessive copper loading often accelerated corrosion and induced adverse cellular responses. Emerging multifunctional architectures demonstrated improved regulation of biological interactions, enabling simultaneous antibacterial, antithrombotic, and proendothelial effects. Overall, copper-based surface technologies represent a versatile platform for soft-tissue implant modification. Future translational progress will require precise control of copper release kinetics and comprehensive long-term in vivo validation to ensure safety and sustained therapeutic performance. From the authors' perspective, the most promising future direction involves multifunctional copper-based hybrid coatings capable of dynamically regulating ion release, host tissue integration, and antibacterial performance simultaneously. Strategies integrating hierarchical architectures, stimulus-responsive release systems, and clinically scalable fabrication methods are expected to play a key role in translating copper-containing surfaces from experimental concepts toward commercially viable soft-tissue biomedical devices.

Copper↗

PubMed2026

Copper is an intestinal habitat filter affecting the gut microbiota interactions with Salmonella Typhimurium.

BACKGROUND: Foodborne pathogens, including Salmonella enterica serovar Typhimurium (S. Typhimurium), pose a significant threat to both human health and livestock productivity. The pandemic S. Typhimurium ST34 clone acquired a genomic island (SGI-4) conferring high copper resistance, an adaptation relevant in the context of the widespread use of copper sulphate at therapeutic levels in pig farming. We investigated how high dietary copper influences the piglet gut microbiota and Salmonella-microbiota interactions that may explain the global spread of S. Typhimurium ST34. RESULTS: An on-farm study combined with faecal shotgun metagenomics revealed that several potential Salmonella competitor species, including Bifidobacterium, Escherichia, and Lactobacillus, were less abundant in piglets on high-copper diets. Anaerobic and aerobic culturing alongside whole genome sequencing of 131 species and copper sulphate susceptibility testing identified copper resistance gene acquisition in selected microbes, particularly within Escherichia. Niche competition assays demonstrated that copper resistance is critical for inter-species competition under high-copper conditions, with Salmonella's Type VI Secretion System providing a distinct advantage over Escherichia in the copper-modified niche. CONCLUSIONS: Our findings suggest that copper supplementation alters the piglet gut environment, impacting competitive dynamics between pathogenic and commensal bacteria, likely to influence the zoonotic transmission of pathogens. Video Abstract.

Animals↗

PubMed2025

Host genetics predominates over gut microbiota in serum copper levels in boars.

Copper is an essential trace element in numerous biological processes; maintaining its homeostasis is crucial for pig health and productivity. In this study, we employed a mixed-effects model to investigate the contributions of host genetics, gut microbiota, and their interactions with serum copper levels in pigs. We further explored potential candidate genes and microbiota associated with copper metabolism. The results demonstrated that host genetics exert a dominant influence on serum copper regulation compared to the effects of the gut microbiota. Furthermore, genome-wide association analysis identified 4 candidate genes, CPHL1, CP, NCEH1, and PDE10A, strongly linked to copper metabolism. By applying multiple association approaches, 10 bacterial genera, such as Blautia, Lachnospiraceae UCG-008, and Ruminococcaceae UCG-007 were found to be significantly correlated with serum copper levels. This research offers novel insights into the genetic and microbial determinants of copper variation in pigs, establishing a foundation for future genetic and microbiota-based strategies aimed at enhancing copper homeostasis and overall livestock health.

Animals↗

PubMed2026

Copper and iron engage distinct metabolic programs for cellular survival.

Copper and iron are redox-active micronutrients with tightly coupled homeostasis, yet how copper modulates iron-dependent stress responses remains unclear. Using Saccharomyces cerevisiae under nutrient-limited conditions, we uncoupled proliferative growth from long-term survival to dissect metal-dependent adaptation. Copper selectively preserved survival without affecting growth, whereas iron showed similar effects. Iron chelation impaired growth and suppressed electron transport chain gene expression; copper partially rescued these defects but required iron availability for its pro-survival activity. Despite this interdependence, copper and iron engaged distinct signaling programs. Iron-dependent survival required a Target of Rapamycin complex 1 (TORC1)-permissive state and was attenuated by rapamycin, whereas copper remained active under TORC1 inhibition. In contrast, copper promoted survival through AMP-activated protein kinase (AMPK) and antioxidant pathways, while iron exhibited context-dependent AMPK reliance. Together, these findings reveal that copper and iron support cellular survival through distinct metabolic programs and suggest that the consequences of micronutrient availability are shaped by the underlying nutrient-sensing and metabolic state of the cell. This framework provides insight into how alterations in micronutrient homeostasis and metabolic signaling may influence cellular resilience during aging.

AMPK↗

PubMed2026

scRNA-seq and bulk RNA-seq reveal the characteristics of macrophage copper metabolism and establish a risk signature in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent malignancy with an urgent need for improved prognostic stratification and treatment-response prediction. This study aimed to explore a macrophage copper metabolism-associated prognostic model and to investigate the relationship between this risk model and the tumor immune microenvironment. METHODS: The FindClusters function was used to analyze cell clusters, and CellChat and CellPhoneDB/LIANA were employed for cell-cell communication analysis. Copper metabolism-related genes were sourced from the MSigDB database. A prognostic risk model was established using least absolute shrinkage and selection operator (LASSO) analysis and multivariate Cox regression analysis, and a nomogram was constructed by integrating the prognostic model with clinicopathological factors. Additional analyses were performed to map the seven model genes in single-cell data, assess model uncertainty and robustness, evaluate macrophage/copper/cuproptosis-related transcriptional programs, and examine the correlations between risk score, immune infiltration and predicted drug sensitivity. RESULTS: Using single-cell RNA sequencing (scRNA-seq) data, we identified four macrophage subpopulations. Macrophages with high SPP1 expression showed close interaction with T cell populations and were associated with copper ion metabolism. By incorporating 141 copper metabolism-related genes and using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort, we constructed a seven-gene risk prediction model. Additional single-cell mapping showed that the model genes were detectable in the HCC single-cell dataset and showed a macrophage-associated expression pattern. The model showed moderate prognostic discrimination in TCGA-LIHC, whereas its external performance was heterogeneous and remained evaluable across external cohorts, with performance varying among datasets. Immune and mechanism-related analyses suggested that the risk signature was associated with macrophage-related infiltration, copper metabolism and cuproptosis-related transcriptional programs. Drug sensitivity analysis nominated Daporinad as a computationally predicted candidate compound, supporting Daporinad as a pharmacogenomic candidate for follow-up investigation. CONCLUSIONS: By integrating scRNA-seq and bulk RNA sequencing (RNA-seq) data, we constructed a macrophage copper metabolism-associated prognostic signature for HCC. The risk score was associated with survival, immune microenvironment features and predicted drug response, providing a transcriptomic framework for risk stratification and therapeutic hypothesis generation.

Hepatocellular carcinoma (HCC)↗

PubMed2026

Ant abaecin-2 is a context-dependent copper-binding effector that can be either inhibitory or protective.

Host defense peptides (HDPs) are important components of the innate immune system that are used to combat pathogens and often rely on binding trace nutrient metals for their function. However, controlling nutrient metals may have other roles in host-symbiont interactions beyond poisoning harmful pathogens. This study characterizes the evolution, structural properties, and biochemical activity of the novel hymenopteran HDP abaecin-2. In myrmicine ants such as the fungus-growing tribe Attini, abaecin-2 has evolved to include an Amino-Terminal Cu(ii) and Ni(ii)-binding (ATCUN) motif, which we hypothesize binds copper, a trace nutrient that is enriched in attine ant colonies. Combined results from mass spectrometry, competitive binding assays, circular dichroism, and NMR indicate that the abaecin-2 peptide lacks a defined secondary structure and can associate with up to 2 Cu(ii) ions, one strongly bound at the ATCUN motif and another weakly bound, likely at a conserved histidine residue. Despite its copper-binding activity, abaecin-2 alone does not exhibit antibacterial activity against Escherichia coli or Bacillus subtilis (models for bacteria that live in ant fungus gardens). However, it synergizes with a model pore-forming peptide cecropin A to inhibit the growth of E. coli, similar to the related peptide abaecin-1. The copper-binding activity conferred by the ATCUN motif also protects copper-sensitive E. coli from excess copper toxicity. The dual context-dependent inhibitory and protective roles for abaecin-2 indicate that this previously under-characterized HDP may be used by attine ants to regulate both harmful and beneficial symbionts.

Journal Article↗

PubMed2026

Ant abaecin-2 is a context-dependent copper-binding effector that can be either inhibitory or protective.

Host defense peptides (HDPs) are important components of the innate immune system that are used to combat pathogens and often rely on metal binding for their function. However, controlling trace nutrients such as transition metals may have other roles in host-symbiont interactions beyond poisoning harmful pathogens. This study characterizes the evolution, structural properties, and biochemical activity of the novel hymenopteran HDP abaecin-2. In myrmicine ants such as the fungus-growing tribe Attini, abaecin-2 has evolved to include an Amino-Terminal Cu(II) and Ni(II)-binding (ATCUN) motif, which we hypothesize may bind copper, a trace nutrient that is enriched in attine ant colonies. Combined results from mass spectrometry, competitive binding assays, circular dichroism, and NMR indicate that the abaecin-2 peptide lacks a defined secondary structure and can associate with up to 2 Cu(II) ions, one strongly bound at the ATCUN motif and another weakly bound, likely at a conserved histidine residue. Despite its copper-binding activity, abaecin-2 alone does not exhibit antibacterial activity against Escherichia coli or Bacillus subtilis (models for bacteria that live in ant fungus gardens). However, it synergizes with a model pore-forming peptide cecropin A to inhibit the growth of E. coli, similar to the related peptide abaecin-1. The copper-binding activity conferred by the ATCUN motif also protects copper-sensitive E. coli from excess copper toxicity. The dual, context-dependent inhibitory and protective roles we propose for abaecin-2 indicate that this previously under-characterized HDP may be used by attine ants to regulate both harmful and beneficial symbionts.

Journal Article↗

PubMed2026

Engineering copper ferrite (CuFe2O4) nanocomposites for enhanced eco-friendly photocatalysis: a systematic critical review on mechanisms, performance, and environmental applications.

Water pollution caused by organic and inorganic contaminants, particularly dyes and pharmaceuticals, represents a major environmental challenge. Advanced oxidation processes based on photocatalysts have emerged as efficient and sustainable approaches for water and wastewater treatment. Copper ferrite (CuFe2O4) is considered a promising photocatalyst owing to its narrow bandgap, visible-light activity, chemical stability, and magnetic properties. Despite extensive experimental investigations, a comprehensive systematic comparison of CuFe2O4-based photocatalysts under diverse operational conditions has remained limited. In this study, a systematic review following PRISMA guidelines was conducted using studies published between January 2014 and November 2025 indexed in Scopus, PubMed, Web of Science, and ScienceDirect. From an initial pool of 397 studies, 98 articles met the inclusion criteria. Key parameters - including pollutant type, pH, catalyst dosage, initial pollutant concentration, irradiation time, light source, and degradation efficiency - were quantitatively compared to identify performance trends and operational optima. The results demonstrate that CuFe2O4-based nanocomposites, particularly heterojunction, Z-scheme, and S-scheme architectures combined with TiO2, g-C3N4, graphene, and metal oxides, achieve high degradation efficiencies (often >90 %) for a wide range of organic pollutants and selected inorganic contaminants (e.g., Cr(VI)). Enhanced charge separation and suppressed electron-hole recombination were identified as the primary factors contributing to improved photocatalytic activity. In addition, the intrinsic magnetic properties of these nanocomposites enable facile catalyst recovery and reuse. In conclusion, CuFe2O4-based nanocomposites, especially those incorporating advanced heterojunction architectures, emerge as highly efficient and magnetically recoverable photocatalytic platforms for sustainable water and wastewater treatment, with strong potential for scalable implementation and real-wastewater applications.

Catalysis↗

PubMed2026

UBE2D4 Upregulation Promotes Cuproptosis Sensitivity in Colorectal Cancer.

BACKGROUND: Cuproptosis, a copper-dependent form of regulated cell death, represents a potential therapeutic vulnerability in colorectal cancer (CRC). However, the regulatory mechanisms governing cuproptosis in CRC remain largely unknown. METHODS: UBE2D4 expression was analyzed in the TCGA-COAD cohort and validated in CRC cell lines (HCT116, HT29) and normal colon epithelial cells (FHC) by qRT-PCR and western blot. Paired CRC and adjacent normal tissues (n = 5) were also examined by western blot. UBE2D4-knockdown HT29 cells were generated by transient siRNA transfection to assess cell viability (CCK-8), migration (wound healing assay), and expression of cuproptosis-related genes (DLAT, HSP70, LIAS) under copper overload conditions (elesclomol+CuSO4). RESULTS: UBE2D4 was significantly upregulated in CRC tissues and cell lines compared to normal controls. In paired clinical samples, western blot confirmed that UBE2D4 protein expression was elevated in tumor tissues, accompanied by increased DLAT, HSP70 and LIAS. Copper overload induced typical cuproptotic mitochondrial morphology and triggered a marked upregulation of UBE2D4, DLAT, and HSP70, alongside downregulation of LIAS. UBE2D4 silencing had no effect on baseline cell viability or migration but significantly rescued cells from copper-induced cytotoxicity. Genetically, UBE2D4 knockdown specifically attenuated the copper-induced elevation of DLAT, while restoring HSP70 and LIAS to near-baseline levels. CONCLUSION: These findings identify UBE2D4 as a genetically upregulated and functionally significant gene in colorectal cancer. Its upregulation correlates with altered expression of cuproptosis-related genes, particularly DLAT, suggesting that UBE2D4 expression status may represent a genetic determinant of cuproptosis sensitivity in CRC. This study provides a genetic basis for stratifying CRC patients who might benefit from copper-based therapeutic strategies.

Humans↗

PubMed2026

A SINE-like insertion in intron 13 of the ATP7A gene is associated with a mild form of Menkes-like disease in a Cavalier King Charles Spaniel.

A 7-month-old intact male Cavalier King Charles Spaniel was presented for persistent glucosuria despite normoglycemia, failure to thrive, chronic diarrhea, and cerebellar ataxia. Fanconi syndrome was diagnosed, but the neurologic abnormalities were not fully explained. As a consequence of the early onset Fanconi syndrome, a hereditary process was suspected. Whole genome sequencing identified a private hemizygous SINE-like insertion into the ATP7A gene, at the end of intron 13, near the start of exon 14. In humans, variants in ATP7A are associated with Menkes disease, a disorder of copper metabolism associated with a spectrum of clinical signs including progressive neurodegeneration and connective tissue abnormalities. Clinically affected dogs with variants in ATP7A have not been reported previously. Although this case appears to represent a mild phenotypic presentation of Menkes-like disease, it raises the possibility that copper disorders aside from copper-associated hepatitis might exist in dogs. Further genetic screening and phenotypic characterization of rare genetic variants associated with copper metabolism would be beneficial to expand our knowledge of copper disorders in dogs and allow potential early intervention and modeling for metabolic diseases in humans.

Animals↗

PubMed2025

Phylogenetically diverse introgression drives subtle population structure in Pacific rockfishes.

Genomic methods have shown that admixture and introgression is common across animal taxa. Pacific rockfishes, genus Sebastes, are group of commercially important species that primarily inhabit inshore, shelf, and slope habitats along the North American west coast. Among these, Copper and Quillback Rockfishes (abbreviated to Copper and Quillback) are closely related species known to hybridize, particularly within the Salish Sea in North America's Pacific Northwest. Here, we investigate genetic population structure and introgression patterns in Copper and Quillback from Alaska to California. Using whole-genome resequencing (WGS) across a broad geographic range, we seek to (1) compare population structure between these species, and (2) assess how introgression affects population structure patterns. Our analyses reveal that Copper exhibit much higher levels of population differentiation compared to Quillback, especially separating Salish Sea samples from all other populations. In contrast, Quillback populations appear to be nearly panmictic, with lower overall differentiation. Surprisingly, we detected signatures of introgression from 13 other rockfish species in Copper and 16 species in Quillback. This introgression was highly regional suggesting hybridization depended on geographic context and congener ranges. Yelloweye Rockfish introgression drives the strongest signal of regional population structure in Quillback. These findings provide novel insights into the range-wide genetic structure of these species and highlight that hybridization in Sebastes is phylogenetically broader than previously appreciated.

Journal Article↗

PubMed2024

Macrothrombocytopenia with leukocyte inclusions in a patient with Wilson disease: a case report and literature review.

BACKGROUND: Wilson disease (WD) is an autosomal recessive disorder caused by homozygous or compound heterozygous mutations in ATP7B. Clinical manifestations primarily involve liver and nervous system lesions, with rarely observed hematologic manifestations. CASE PRESENTATION: In the present case, a patient with WD presented with thrombocytopenia, giant platelets, and Döhle-like cytoplasmic inclusions in the leukocytes. Initially, the May-Hegglin anomaly was considered; however, whole-exome sequencing did not reveal any mutation in the MYH9 gene but a heterozygous mutation was found in (C.2804 C > T, p.T935M) in the ATP7B gene. After two years, the patient developed tremors in his hands, lower limb stiffness, and foreign body sensation in the eyes. Additionally, Kayser-Fleischer rings in the corneal limbus were detected by slit-lamp examination. Copper metabolism test indicated a slight decrease in serum ceruloplasmin. Transmission electron microscopy revealed that the inclusion bodies of leukocytes were swollen mitochondria. Mass spectrometry analysis showed that the copper levels were almost 20-fold higher in the leukocytes of the patient than in those of the control group. Based on the Leipzig scoring system, a diagnosis of WD was confirmed. Zinc sulfate treatment ameliorated the patient's symptoms and enhanced platelet, serum ceruloplasmin, and albumin levels. CONCLUSIONS: In conclusion, this case represents the first documented instance of WD presenting as thrombocytopenia, giant platelets, and Döhle-like cytoplasmic inclusions in the leukocytes. Excessive cellular copper accumulation likely underlies these findings; however, understanding precise mechanisms warrants further investigation.

Humans↗

PubMed2024

Urinary Metal Levels, Cognitive Test Performance, and Dementia in the Multi-Ethnic Study of Atherosclerosis.

IMPORTANCE: Metals are established neurotoxicants, but evidence of their association with cognitive performance at low chronic exposure levels is limited. OBJECTIVE: To investigate the association of urinary metal levels, individually and as a mixture, with cognitive tests and dementia diagnosis, including effect modification by apolipoprotein ε4 allele (APOE4). DESIGN, SETTING, AND PARTICIPANTS: The multicenter prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA) was started from July 2000 to August 2002, with follow-up through 2018. A total of 6303 MESA participants were included. Data analysis was performed from October 12, 2023, to June 13, 2024. EXPOSURE: Urine samples were collected at baseline (2000-2002), and arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc levels were measured in 2020-2022. MAIN OUTCOMES AND MEASURES: Digit Symbol Coding (DSC) (n = 3819) (possible score range, 0-133), Cognitive Abilities Screening Instrument (CASI) (n = 3918) (possible score range, 0-100), and Digit Span (DS) (n = 4176) (possible score range, 0-30) cognitive tests were administered in 2010-2012; higher scores of each test indicate increasing levels of positive response. RESULTS: A total of 6303 participants were followed up for dementia diagnosis through 2018. The median age at baseline was 60 (IQR, 53-70) years, and 3303 participants (52.4%) were female. The median cognitive scores were 51 (IQR, 38-64) for DSC, 90 (IQR, 84-95) for CASI, and 15 (IQR, 12-18) for DS. There were 559 cases of dementia through the follow-up period. Inverse associations with DSC were identified: mean differences in z scores per IQR increase in metal levels were -0.03 (95% CI, -0.07 to 0.00) for arsenic, -0.05 (95% CI, -0.09 to -0.004) for cobalt, -0.05 (95% CI, -0.07 to -0.02) for copper, -0.04 (95% CI, -0.08 to -0.001) for uranium, and -0.03 (95% CI, -0.06 to -0.01) for zinc. Among 1058 APOE4 carriers, manganese was also inversely associated with DSC. The joint mean difference of DSC comparing percentile 95th with the 25th of the 9-metal mixture was -0.30 (95% CI, -0.47 to -0.14) for APOE4 carriers and -0.10 (95% CI, -0.19 to -0.01) for noncarriers. Arsenic, cadmium, cobalt, copper, tungsten, uranium, and zinc were individually associated with dementia, with hazard ratios per IQR of metal ranging from 1.15 (95% CI, 1.03-1.29) for tungsten to 1.46 (95% CI, 1.06-2.02) for uranium. The joint hazard ratio of dementia comparing percentiles 95th with the 25th of the 9-metal mixture was 1.71 (95% CI, 1.24-3.89), with no significant difference by APOE4 status. CONCLUSIONS AND RELEVANCE: In this study, participants with higher concentrations of metals in their urine, compared with those with lower concentrations, had worse performance on cognitive tests and greater likelihood of developing dementia. The findings of this multicenter multiethnic cohort study might inform screening and potential interventions for prevention of dementia based on individuals' metal exposure levels and genetic profiles.

Humans↗

PubMed2026

Covalent surface coordination enables efficient and stable formaldehyde-water co-electrolysis over non-stoichiometric cuprous oxide.

The activity-stability trade-off of copper-based oxide catalysts in formaldehyde oxidation remains a fundamental challenge. Here, we resolve this trade-off by grafting N-heterocyclic carbenes (NHCs) onto non-stoichiometric Cu2+1O nanocubes (denoted as Cu2+1O, a Cu+-rich single-phase oxide) through covalent CuC bonds. This molecular surface coordination strategy delivers two concurrent benefits. First, strong σ-electron donation from NHCs shifts the Cu d-band center from -2.106 eV to -2.416 eV, weakening intermediate adsorption and lowering the reaction free-energy change of the rate-determining step (CHOOH⁎ desorption) from 2.56 eV to 1.38 eV. Second, the covalent CuC anchors suppress copper leaching in alkaline electrolyte by a factor of 160 (from 8 mg L-1 to 0.05 mg L-1 over 100 h). The resulting Cu2+1O-NHC catalyst drives formaldehyde oxidation at an onset potential of 0.1 V vs. RHE (Tafel slope: 590 ± 2 mV dec-1, versus 96 ± 3 mV dec-1 for unmodified Cu2+1O; mean ± SD, n = 3), achieving near-unity Faradaic efficiency for both formate (98.65 ± 0.32%) and anodic H2 evolution from CH bond cleavage (99.14 ± 0.28%). Isotope-labeled DEMS confirms that anodic H₂ originates predominantly from the CH bond of formaldehyde, as no HD or D2 was detected when the reaction was performed in D2O. After 100 h of continuous operation, the cubic morphology remains largely intact. This work establishes covalent surface coordination as a promising molecular strategy to decouple activity and stability in oxide electrocatalysts, potentially extendable beyond the specific case of Cu2+1O for aldehyde oxidation.

Copper oxide catalyst↗

PubMed2025

Discovery of Isonitrile Lipopeptide Chalkophores from Pathogenic Mycobacteria.

The virulence-associated isonitrile lipopeptide (INLP) biosynthetic gene cluster is conserved across Mycobacterium tuberculosis and many nontuberculous mycobacteria (NTM) pathogens, yet the corresponding mycobacterial metabolites have not been fully characterized, and their biological functions are still debated. Here, we report a precursor neutral loss chromatography based mass spectrometry strategy that enables the targeted discovery of INLPs from Mycobacterium fortuitum, a fast-growing NTM pathogen. By monitoring a characteristic neutral loss of 27.1 Da corresponding to hydrogen cyanide, we identified a family of INLPs directly from bacterial culture extracts. Structural elucidation of a representative compound using NMR and high-resolution MS revealed a distinctive terminal methylated carboxyl group, contrasting with previously reported INLPs bearing linear alcohol, acetal, or cyclic motifs. Bioinformatic analysis and in vitro enzymatic assays identified a methyltransferase encoded within the INLP BGC responsible for methyl ester formation. Furthermore, metal-binding assays demonstrated selective chelation of Cu(I) and Cu(II) by the isolated INLP, but no detectable interaction with Zn(II), suggesting a role in copper homeostasis. These findings represent the first full structural characterization of an INLP from pathogenic mycobacteria, expand our understanding of the enzymes involved in INLP modification, and unequivocally support the copper-binding activity of INLPs from these pathogens.

Lipopeptides↗

PubMed2025

The molecular mechanism of cuproptosis and research progress in pancreatic diseases.

PURPOSE: Cuproptosis has been proven to be a novel mode of cell death, distinct from other types of cell death such as necrosis, ferroptosis, pyroptosis, and apoptosis. This study aims to systematically review the molecular mechanisms of cuproptosis in recent years and its research progress in pancreatic diseases. METHODS: By searching PubMed and Web of Science databases, 113 key literatures were included for thematic analysis, covering the molecular mechanism of cuproptosis and its role in the occurrence and development of pancreatic cancer, acute and chronic pancreatitis, diabetes, pancreatic cyst, pancreatic injury and pancreatic neuroendocrine tumor. RESULTS: Cuproptosis refers to the accumulation of copper ions in cells, which leads to instability of ferritin and aggregation of acylated proteins, resulting in oxidative stress-related cell death. Recent studies have shown that cuproptosis plays an important role in the occurrence and development of various pancreatic diseases, such as pancreatic cancer, acute and chronic pancreatitis, diabetes, pancreatic cysts, pancreatic injuries and pancreatic neuroendocrine tumor. The inducers of cuproptosis, such as disulfiram, chloroquinolones, and perilla phenols, alleviate pancreatic cancer by promoting cell cuproptosis. Copper chelators such as tetraethylenepentamine and tetrathiomolybdate promote the recovery of pancreatic injury by inhibiting cell cuproptosis. CONCLUSIONS: Cuproptosis plays a crucial role in the pathogenesis of pancreatic diseases. Further research on the cuproptosis pathway may become a potential target for the treatment of pancreatic diseases.

Animals↗

PubMed2025

MmoD and MmoG Are Crucial for the Synthesis of Soluble Methane Monooxygenase in Methanotrophs.

Soluble methane monooxygenase (sMMO) from methanotrophs has been extensively investigated for decades. However, major knowledge gaps persist regarding the synthesis mechanism of sMMO, particularly concerning the ambiguous roles of mmoD and mmoG in the sMMO gene cluster. Here, the functions of mmoD and mmoG were investigated in a model methanotrophic strain, Methylotuvimicrobium buryatense 5GB1C. Both genes were found to be essential for the functional expression of sMMO. Genetic and biochemical data supported the hypothesis that MmoG acts as a folding chaperone for both MmoX and MmoR, while MmoD serves as an assembly chaperone for the hydroxylase component. The functional expression of sMMO in Escherichia coli was achieved in an mmoD- and mmoG-dependent manner. In addition, deletion of mmoD dramatically reduced the transcription of the sMMO cluster in M. buryatense 5GB1C, implying that MmoD may regulate the sMMO cluster via an unknown mechanism. Knockout of neither mmoD nor mmoG abolished the essential feature of "copper switch", indicating that they do not serve as the initial regulators of "copper switch". These results demonstrate the crucial roles of mmoD and mmoG in sMMO synthesis and offer new insights into heterologous expression of sMMO.

Oxygenases↗