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Copper (Cu) is a redox-active micronutrient that is both essential and toxic. Its cellular homeostasis is critical for supporting cuproprotein maturation while avoiding excessive oxidative stress. The Cu importer CcoA is the prototype of the widespread CalT subfamily of the MFS-type transporters. Hence, understanding its molecular mechanism of function is significant. Here, we show that CcoA undergoes a thiol:disulfide oxidoreduction cycle, which is important for its Cu import activity. CcoA belongs to the widely distributed bacterial copper (Cu) importer subfamily CalT ( C co A - l ike T ransporters) of the Major Facilitator Superfamily (MFS) and provides cytoplasmic Cu needed for cbb 3 -type cytochrome c oxidase ( cbb 3 -Cox) biogenesis. Earlier studies have supported a 12-transmembrane helix (TMH) topology of CcoA with the well-conserved Met 233 xxxMet 237 and His 261 xxxMet 265 motifs in its TMH7 and TMH8, respectively. Of these residues, Met 233 and His 261 are essential for Cu uptake and cbb 3 -Cox production, whereas Met 237 and Met 265 contribute partly to these processes. CcoA also contains five Cys residues of unknown role and, remarkably, its structural models predict that three of these are exposed to the highly oxidizing periplasm. Here, we first demonstrate that elimination of both Met 237 and Met 265 completely abolishes Cu uptake and cbb 3 -Cox production, indicating that CcoA requires at least one of these two Met residues for activity. Second, using scanning mutagenesis to probe plausible metal-interacting Met, His, and Cys residues of CcoA, we found that the periplasm-exposed Cys 49 located at the end of TMH2, the Cys 247 on a surface loop between TMH7 and THM8, and the C 367 located at the end of TMH11 are important for CcoA function. Analyses of the single and double Cys mutants revealed the occurrence of a disulfide bond in CcoA in vivo , possibly related to conformational changes it undergoes during Cu import as MFS-type transporter. Our overall findings suggest a model linking Cu import for cbb 3 -Cox biogenesis with a thiol:disulfide oxidoreduction step, advancing our understanding of the mechanisms of CcoA function. IMPORTANCE Copper (Cu) is a redox-active micronutrient that is both essential and toxic. Its cellular homeostasis is critical for supporting cuproprotein maturation while avoiding excessive oxidative stress. The Cu importer CcoA is the prototype of the widespread CalT subfamily of the MFS-type transporters. Hence, understanding its molecular mechanism of function is significant. Here, we show that CcoA undergoes a thiol:disulfide oxidoreduction cycle, which is important for its Cu import activity.

Copper (Cu) could be seriously hazardous when present at excessive levels, despite its vital contribution to various cellular processes. Selenium-enriched yeast (SeY) was reported to improve the health and metabolic status in broiler chicken. Hence, our study was endeavored to illustrate the mitigating efficacy of SeY on Cu-induced hepatic and renal damage. Cobb chicks aged 1 day were allocated into four experimental groups and offered a basal diet, SeY (0.5 mg/kg), CuSO 4 (300 mg/kg), or SeY plus CuSO 4 in their diets for 42 days. Our results revealed that SeY supplement antagonized significantly the Cu accumulation in livers and kidneys of exposed birds. Marked declines were also detected in the AST, ALT, urea, and creatinine levels, besides marked increases in total protein, glycerides, and cholesterol in the SeY-supplemented group. Moreover, enhancement of cellular antioxidant biomarkers (superoxide dismutase, CAT, GPx, and GSH) along with lowered MDA contents were achieved by SeY in hepatic and renal tissues. Further, SeY exerted a noteworthy anti-inflammatory action as indicated by decreased inflammatory biomarkers (IL-1β and TNF-α) and NO levels in both organs. Noticeable histopathological alterations of both organs further validated the changes in the markers mentioned above. To sum up, our findings indicate that SeY can be considered a potential feed supplement for alleviating Cu-induced hepatic and renal damage in broilers, possibly via activation of antioxidant molecules and lessening the inflammatory stress.

The study was conducted to investigate the effects of copper sources and levels on lipid profiles, immune parameters, antioxidant defenses, and trace element contents of meat and liver in Arbor Acres broilers. A total of 504 male broilers were randomly divided into 7 groups with 6 replicates per group and 12 broilers per replicate. The experiment was used in a 3 × 2 + 1 factorial experiment design; broilers in the control group were fed a basal diet, and broilers in the other six groups were fed basal diets supplemented with 3 sources (copper sulfate, tribasic copper chloride, and copper methionate) and 2 levels (10 and 20 mg/kg). The results showed that the levels of cholesterol and low-density lipoprotein cholesterol in broilers were significantly decreased with the increase of dietary copper level ( P <  0.05). Serum IL-6 and IgA contents, ceruloplasmin and GSH-Px activities, and liver copper contents of broilers increased significantly with dietary copper levels ( P <  0.05). Compared with the control group, dietary copper supplementation significantly decreased serum cholesterol ( P <  0.05) and significantly increased serum IL-6, ceruloplasmin, SOD, GSH-Px, and liver copper ( P <  0.05). Dietary supplementation of basic copper chloride and copper methionate significantly decreased low-density lipoprotein cholesterol content and liver iron content ( P  < 0.05). In conclusion, dietary copper supplementation can effectively reduce serum cholesterol content and improve immune and antioxidant functions in broilers. Adding 20 mg/kg copper to broiler diet can increase the copper content in the liver, but it will not affect the copper content in the chicken.

An air-stable supported Cu(I) catalyst, CuI@PS-Phen, was designed and synthesized. CuI@PS-Phen can efficiently catalyze the click polymerization of diynes a and diazides b to produce soluble and thermally stable polytriazoles with high molecular weights ( M w up to 30800), and low copper residue content (down to 190 ppm) in high yields (up to 94.2%) under mild reaction conditions without the exclusion of oxygen.

Waste copper-containing paint residue (WCPR) represents a typical hazardous waste containing both toxic organic substances and toxic heavy metals, but there are few reports on the recycling of heavy metals. The recovery of Cu from WCPR by H2SO4 leaching–extraction–stripping has the advantages of eco-friendliness, simplicity of operation, and high value-added product. The results show that under the optimal conditions, the leaching rate of Cu in WCPR is 94.31% (18.02 g/L), while the extraction and stripping rates of Cu in the leaching solution are 99.46 and 95.32%, respectively. Due to the high concentration of Cu2+ with fewer impurities in the stripping solution, the stripping solution is heated, evaporated, cooled, and crystallized to successfully produce high-purity dark blue CuSO4 crystal, accomplishing the high-value recycling of Cu in WCPR. In addition, the leach residue of WCPR contains acrylic resin and SiO2, which can be used in cement kilns for incineration, thus realizing the overall recycling and utilization of WCPR.

Copper smelting dust is a heterogeneous by-product of pyrometallurgical processing containing sulfate- and arsenic-bearing components, which accounts for its high chemical stability and environmental hazard. In this context, mechanochemical activation is considered a promising approach for initiating structural and phase transformations in such systems. The aim of this study was to investigate the effect of high-energy planetary milling in the “dust–Na2S” and “dust–Na2S–NaOH” systems on changes in the phase composition of arsenic-bearing dust. The samples were prepared by dry mechanochemical activation in a planetary mill for 15 and 30 min with varying reagent contents. According to X-ray diffraction analysis, PbSO4 and ZnSO4·H2O remain the major phases in the binary system, while the formation of elemental sulfur (S6) and the arsenic sulfide phase (As4S4) is observed against a decrease in the As2O3 content. In the presence of NaOH, a more pronounced redistribution of arsenic species is observed, accompanied by the appearance of a Na-containing As–O–S phase, preliminarily identified as Na3AsO2S2, and a further decrease in the proportion of As2O3. Thermodynamic analysis indicates the energetic favorability of arsenic sulfidation when the oxidative contribution of the air atmosphere during milling is taken into account. The obtained results refine the possible mechanochemical pathways of arsenic transformation and may be used to substantiate preliminary activation regimes prior to subsequent leaching.

Copper anodic slime is often smelted with lead to improve silver and gold recovery, generating a fine lead-rich fly ash that contains notable amounts of selenium and tellurium. Due to its high lead content and sub-micron particle size, this residue poses significant environmental and occupational health risks. This study evaluates sodium carbonate (Na2CO3) leaching as an environmentally benign pre-treatment aimed at partially removing selenium and tellurium while stabilizing lead through carbonate formation. The goal is detoxification rather than maximum metal recovery, enabling safer disposal or subsequent recycling. A central composite design (CCD) in Design-Expert software (Version 12) was used to assess the effects of Na2CO3 concentration, temperature, solid-to-liquid ratio, and time on selenium and tellurium dissolution. Selenium recovery reached up to 53.9%, while tellurium recovery peaked at approximately 33.9%. Scanning electron microscopy showed the dust to consist mainly of semi-spherical and elongated particles, with lead carbonate forming preferentially on particle surfaces during leaching. Energy-dispersive spectroscopy confirmed conversion of lead sulfate phases to lead carbonate, which increasingly restricted selenium and tellurium dissolution. Kinetic evaluation suggested selenium leaching follows mixed control involving both surface reaction and diffusion through product layers, whereas tellurium dissolution lacked consistent kinetic behavior. Thermodynamic calculations supported the stabilization of lead as cerussite (PbCO3), indicating improved environmental safety. The overall dissolution trends were successfully represented using an apparent Shrinking Core Model (SCM) based on measurements collected at 20 °C, 60 °C, and 100 °C.

The role of copper in cancer treatment is multifaceted, with copper homeostasis-related genes associated with both breast cancer prognosis and chemotherapy resistance. Interestingly, both elimination and overload of copper have been reported to have therapeutic potential in cancer treatment. Despite these findings, the exact relationship between copper homeostasis and cancer development remains unclear, and further investigation is needed to clarify this complexity. The pan-cancer gene expression and immune infiltration analysis were performed using the Cancer Genome Atlas Program (TCGA) dataset. The R software packages were employed to analyze the expression and mutation status of breast cancer samples. After constructing a prognosis model to separate breast cancer samples by LASSO-Cox regression, we examined the immune statement, survival status, drug sensitivity and metabolic characteristics of the high- and low-copper related genes scoring groups. We also studied the expression of the constructed genes using the human protein atlas database and analyzed their related pathways. Finally, copper staining was performed with the clinical sample to investigate the distribution of copper in breast cancer tissue and paracancerous tissue. Pan-cancer analysis showed that copper-related genes are associated with breast cancer, and the immune infiltration profile of breast cancer samples is significantly different from that of other cancers. The essential copper-related genes of LASSO-Cox regression were ATP7B (ATPase Copper Transporting Beta) and DLAT (Dihydrolipoamide S-Acetyltransferase), whose associated genes were enriched in the cell cycle pathway. The low-copper related genes scoring group presented higher levels of immune activation, better probabilities of survival, enrichment in pathways related to pyruvate metabolism and apoptosis, and higher sensitivity to chemotherapy drugs. Immunohistochemistry staining showed high protein expression of ATP7B and DLAT in breast cancer samples. The copper staining showed copper distribution in breast cancer tissue. This study displayed the potential impacts of copper-related genes on the overall survival, immune infiltration, drug sensitivity and metabolic profile of breast cancer, which could predict patients' survival and tumor statement. These findings may serve to support future research efforts aiming at improving the management of breast cancer.

Cuproptosis caused by copper overload is mediated by a novel regulatory mechanism that differs from previously documented mechanisms regulating cell death. Cells dependent on mitochondrial respiration showed increased sensitivity to a copper ionophore elesclomol that induced cuproptosis. Maternal embryonic leucine zipper kinase(MELK) promotes tumorigenesis and tumor progression through the PI3K/mTOR pathway, which exerts its effects partly by targeting the pyruvate dehydrogenase complex(PDHc) and reprogramming the morphology and function of mitochondria. However, the role of MELK in cuproptosis remains unclear. Here, we validated that elevated MELK expression enhanced the activity of PI3K/mTOR signaling and subsequently promoted Dihydrolipoamide S-Acetyltransferase (DLAT) expression and stabilized mitochondrial function. This regulatory effect helped to improve mitochondrial respiration, eliminate excessive intracellular reactive oxygen species (ROS), reduce intracellular oxidative stress/damage and the possibility of mitochondria-induced cell fate alternations, and ultimately promote the progression of HCC. Meanwhile, elesclomol reduced translocase of outer mitochondrial membrane 20(TOM 20) expression and increased DLAT oligomers. Moreover, the above changes of MELK to HCC were abolished by elesclomol. In conclusion, MELK enhanced the levels of the cuproptosis-related signature(CRS) gene DLAT (especially the proportion of DLAT monomer) by activating the PI3K/mTOR pathway, thereby promoting elesclomol drug resistance, altering mitochondrial function, and ultimately promoting HCC progression.

Copper is a trace element essential for numerous biological activities, whereas the mitochondria serve as both major sites of intracellular copper utilization and copper reservoir. Here, we investigated the impact of mitochondrial copper overload on the tricarboxylic acid cycle, renal senescence and fibrosis. We found that copper ion levels are significantly elevated in the mitochondria in fibrotic kidney tissues, which are accompanied by reduced pyruvate dehydrogenase (PDH) activity, mitochondrial dysfunction, cellular senescence and renal fibrosis. Conversely, lowering mitochondrial copper levels effectively restore PDH enzyme activity, improve mitochondrial function, mitigate cellular senescence and renal fibrosis. Mechanically, we found that mitochondrial copper could bind directly to lipoylated dihydrolipoamide acetyltransferase (DLAT), the E2 component of the PDH complex, thereby changing the interaction between the subunits of lipoylated DLAT, inducing lipoylated DLAT protein dimerization, and ultimately inhibiting PDH enzyme activity. Collectively, our study indicates that mitochondrial copper overload could inhibit PDH activity, subsequently leading to mitochondrial dysfunction, cellular senescence and renal fibrosis. Reducing mitochondrial copper overload might therefore serve as a strategy to rescue renal fibrosis.