Role of copper chelating agents: between old applications and new perspectives in neuroscience

The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays an important role in the central nervous system, where it is associated with glutamatergic signaling, and it is widely involved in inflammatory processes. Thus, diseases involving copper(Ⅱ) dyshomeostasis often have neurological symptoms, as exemplified by Alzheimer's and other diseases(such as Parkinson's and Wilson's diseases). Moreover, imbalanced copper ion concentrations have also been associated with diabetes and certain types of cancer, including glioma. In this paper, we propose a comprehensive overview of recent results that show the importance of these metal ions in several pathologies, mainly Alzheimer's disease, through the lens of the development and use of copper chelators as research compounds and potential therapeutics if included in multi-target hybrid drugs. Seeing how copper homeostasis is important for the well-being of animals as well as humans, we shortly describe the state of the art regarding the effects of copper and its chelators in agriculture, livestock rearing, and aquaculture, as ingredients for the formulation of feed supplements as well as to prevent the effects of pollution on animal productions.

Role of copper in central nervous system physiology and pathology

Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.

Effects of wood species and retention levels on removal of copper,chromium,and arsenic from CCA-treated wood using sodium hypochlorite

Chemical extraction, bioremediation, and electrodialytic processes have been extensively studied for removal of copper, chromium, and arsenic from wood treated with chromated copper arsenate （CCA）. However, one problem has not been addressed： the effects of wood species and retention levels on remediation efficiency. The objectives of this study were to investigate the effects of wood species and retention levels on removal of copper, chromium, and arsenic from CCA-treated wood samples using sodium hypochlorite. Our results showed that sodium hypochlorite （NaOC1） was very effective for removal of copper, chromium, and arsenic from CCA-C treated milled wood samples for all three species used in this study. The Cu, Cr, and As extraction efficiencies for red pine were 95 % Cu, 97 % Cr and 94 % As, for maple were 95 % Cu, 97 % Cr, and 98 % As at 4.0 kg m-3 retention levels, and for aspen were 95 % Cu, 92% Cr, and 91% As at 9.6 kg m-3 retention level, respectively. However, the results showed that wood species and initial retention levels of CCA-treated wood products played very impor- tant roles in terms of removal of Cu, Cr, and As.

Copper Metabolism and Cuproptosis:Molecular Mechanisms and Therapeutic Perspectives in Neurodegenerative Diseases

Copper is an essential trace element,and plays a vital role in numerous physiological processes within the human body.During normal metabolism,the human body maintains copper homeostasis.Copper deficiency or excess can adversely affect cellular function.Therefore,copper homeostasis is stringently regulated.Recent studies suggest that copper can trigger a specific form of cell death,namely,cuproptosis,which is triggered by excessive levels of intracellular copper.Cuproptosis induces the aggregation of mitochondrial lipoylated proteins,and the loss of iron-sulfur cluster proteins.In neurodegenerative diseases,the pathogenesis and progression of neurological disorders are linked to copper homeostasis.This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases.This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.

Influences of copper on solidification structure and hardening behavior of high chromium cast irons

The influences of copper on microstructure and the hardening behavior of high chromium cast irons subjected to sub-critical treatment were investigated. The results show that the microstructure of the as-cast high chromium cast irons consists of retained austenite, martensite and M1C3 type eutectic carbide. When copper is added into high chromium cast irons, austenite and carbide contents are increased. The increased addition of copper content from 0% to 1.84% leads to the increase of austenite and carbide from 15.9% and 20. 0% to 61.0% and 35.5% , respectively. In the process of sub-critical treatment, the retained austenite in the matrix can be precipitated into secondary carbides and then transforms into martensite in cooling process, which causes the secondary hardening of the alloy under sub-critical treatment. High chromium cast irons containing copper in sub-critical treatment appear the second hardening curve peak due to the precipitation of copper from supersaturated matrix.

Adsorption of copper(Ⅱ) and chromium(Ⅵ) on diaspore

The adsorption of Cu(Ⅱ)and Cr(Ⅵ)on diaspore was studied with the help of X-ray diffraction analysis,BET measurement,zeta potential measurement and atomic adsorption spectrometry.The adsorption equilibrium almost reaches within 60 min.The adsorption isotherms of Cu(Ⅱ)and Cr(Ⅵ)could be well described by the Langmuir equation.The adsorption capacities of Cu(Ⅱ)and Cr(Ⅵ)are 1.944 and 1.292 mg/g,respectively.The adsorption percentage of Cr(Ⅱ)increases with the increment of solution pH,but the adsorption percentage of Cr(Ⅵ)decreases.This could be explained by zeta potential theoretical and electrostatic attraction between metal ions and diaspore surface.

Design of low-alloying and high-performance solid solution-strengthened copper alloys with element substitution for sustainable development

Solid solution-strengthened copper alloys have the advantages of a simple composition and manufacturing process,high mechanical and electrical comprehensive performances,and low cost;thus,they are widely used in high-speed rail contact wires,electronic component connectors,and other devices.Overcoming the contradiction between low alloying and high performance is an important challenge in the development of solid solution-strengthened copper alloys.Taking the typical solid solution-strengthened alloy Cu-4Zn-1Sn as the research object,we proposed using the element In to replace Zn and Sn to achieve low alloying in this work.Two new alloys,Cu-1.5Zn-1Sn-0.4In and Cu-1.5Zn-0.9Sn-0.6In,were designed and prepared.The total weight percentage content of alloying elements decreased by 43%and 41%,respectively,while the product of ultimate tensile strength(UTS)and electrical conductivity(EC)of the annealed state increased by 14%and 15%.After cold rolling with a 90%reduction,the UTS of the two new alloys reached 576 and 627MPa,respectively,the EC was 44.9%IACS and 42.0%IACS,and the product of UTS and EC(UTS×EC)was 97%and 99%higher than that of the annealed state alloy.The dislocations proliferated greatly in cold-rolled alloys,and the strengthening effects of dislocations reached 332 and 356 MPa,respectively,which is the main reason for the considerable improvement in mechanical properties.

Green-synthesized, biochar-supported nZVI from mango kernel residue for aqueous hexavalent chromium removal: Performance, mechanism and regeneration

A biochar-supported green nZVI(G-nZVI@MKB)composite was synthesized using mango kernel waste with“dual identity”as reductant and biomass of biochar.The G-nZVI@MKB with a Fe/C mass ratio of 2.0(G-nZVI@MKB2)was determined as the most favorable composite for hexavalent chromium(Cr(VI))removal.Distinct influencing parameters were discussed,and 99.0%of Cr(VI)removal occurred within 360 min under these optimized parameters.Pseudo-second order kinetic model and intra-particle diffusion model well depicted Cr(VI)removal process.The XRD,FTIR,SEM,and XPS analyses verified the key roles of G-nZVI and functional groups,as well as the primary removal mechanisms involving electrostatic attraction,reduction,and complexation.G-nZVI@MKB2 exhibited good stability and reusability with only a 16.4%decline in Cr(VI)removal after five cycles.This study offered evidence that mango kernel could be recycled as a beneficial resource to synthesize green nZVI-loaded biochar composite for efficient Cr(VI)elimination from water.

Editorial Commentary:Copper Homeostasis in Neurodegenerative Diseases

Copper,as an essential trace nutrient,plays a crucial role in biological processes such as mitochondrial respiration,antioxidant stress response,and the synthesis of biomolecules.Typically,cellular copper concentrations are maintained at very low levels,a pattern also observed in cancer cells to prevent adverse consequences of copper overload,such as cuproptosis.This involves copper dependency,accumulation of lipidated proteins,and a reduction in Fe-S cluster proteins[1].Various neurodegenerative diseases are associated with imbalances in copper homeostasis.

Solidification/Stabilization of Chromium in Red Mud-based Geopolymer

Up to 1.5wt%of Cr(Ⅲ)salts(CrCl_(3),and Cr_(2)O_(3))and Cr(Ⅵ)salts(Na_(2)CrO_(4),and CaCr_(2)O_(7))were incorporated into red mud-based geopolymers,respectively.The solidification/stabilization,compressive strength,and durability of the Cr-containing geopolymers were investigated.The experimental results indicate that the red mud-based geopolymer could effectively solidify/stabilize different types of Cr salts with solidification/stabilization rates of above 99.61%.Geopolymers are environmentally safe when the dosage of CaCr_(2)O_(7)is≤1.0wt%,or the dosage of CrCl_(3),Cr_(2)O_(3),and Na_(2)CrO_(4)is≤1.5wt%,respectively.The effects of Cr salts on the compressive strength varies with the type and content of Cr salts.The freeze-thaw cycle is more destructive to geopolymer properties than sulfate attack or acid rain erosion.The solidification/stabilization of Cr is mainly attributed to the following reasons:a)The chemical binding of Cr is related to the formation of Cr-containing hydrates(eg,magnesiochromite((Mg,Fe)(Cr,Al)_(2)O_(4)))and doping into N-A-S-H gel and C-A-S-H gel framework;b)The physical effect is related to the encapsulation by the hydration products(e g,N-A-S-H gel and C-A-S-H gel).This study provides a reference for the treatment of hazardous Cr-containing wastes by solid waste-based geopolymers.

Detection of Al, Mg, Ca, and Zn in copper slag by LIBS combined with calibration curve and PLSR methods

The precise measurement of Al, Mg, Ca, and Zn composition in copper slag is crucial for effective process control of copper pyrometallurgy. In this study, a remote laser-induced breakdown spectroscopy(LIBS) system was utilized for the spectral analysis of copper slag samples at a distance of 2.5 m. The composition of copper slag was then analyzed using both the calibration curve(CC) method and the partial least squares regression(PLSR) analysis method based on the characteristic spectral intensity ratio. The performance of the two analysis methods was gauged through the determination coefficient(R^(2)), average relative error(ARE), root mean square error of calibration(RMSEC), and root mean square error of prediction(RMSEP). The results demonstrate that the PLSR method significantly improved both R^(2) for the calibration and test sets while reducing ARE, RMSEC, and RMSEP by 50% compared to the CC method. The results suggest that the combination of LIBS and PLSR is a viable approach for effectively detecting the elemental concentration in copper slag and holds potential for online detection of the elemental composition of high-temperature molten copper slag.

Interphase migration and enrichment of lead and zinc during copper slag depletion

An interphase migration and enrichment model of lead and zinc during molten copper slag depletion was established.The occurrence of various components in copper slag was predicted using sulfur-oxygen potential calculations and confirmed through high-temperature experiments.The recovery rate of copper can reach 90.13%under the optimal conditions of 1200°C,an iron to silicon mass ratio of 1.0,3 wt.%ferrous sulfide,and a duration of 45 min.Lead(54.07 wt.%)and zinc(17.42 wt.%)are found in the flue dust as lead sulfate,lead sulfide,and zinc oxide,while copper matte contains lead(14.44 wt.%)and zinc sulfide(1.29 wt.%).The remaining lead and zinc are encapsulated as oxides within the fayalite phase.

Effective Elimination of Hazardous Chromium (VI) Using Periodic Elements and Contemporary Adsorption Methods by Using Magnesium Ferrite Nanoparticle: A Review

A well-known hazardous metal and top contaminant in wastewater is hexavalent chromium. The two forms of most commonly found chromium are chromate ( CrO 4 2− ) and dichromate ( Cr 2 O 7 2− ). Leather tanning, cooling tower blow-down, plating, electroplating, rinse water sources, anodizing baths etc. are the main sources of Cr (VI) contamination. The Cr (VI) is not only non-biodegradable in the environment but also carcinogenic to living population. It is still difficult to treat Cr contaminated waste water effectively, safely, eco-friendly, and economically. As a result, many techniques have been used to treat Cr (VI)-polluted wastewater, including adsorption, chemical precipitation, coagulation, ion-exchange, and filtration. Among these practices, the most practical method is adsorption for the removal of Cr (VI) from aqueous solutions, which has gained widespread acceptance due to the ease of use and affordability of the equipment and adsorbent. It has been revealed that Fe-based adsorbents’ oxides and hydroxides have high adsorptive potential to lower Cr (VI) content below the advised threshold. Fe-based adsorbents were also discovered to be relatively cheap and toxic-free in Cr (VI) treatment. Fe-based adsorbents are commonly utilized in industry. It has been discovered that nanoparticles of Fe-, Ti-, and Cu-based adsorbents have a better capacity to remove Cr (VI). Cr (VI) was effectively removed from contaminated water using mixed element-based adsorbents (Fe-Mn, Fe-Ti, Fe-Cu, Fe-Zr, Fe-Cu-Y, Fe-Mg, etc.). Initial findings suggest that Cr (VI) removal from wastewater may be accomplished by using magnesium ferrite nanomaterials as an efficient adsorbent.

Pyrolysis of Copper Phthalocyanine as Non-noble Metal Electrocatalysts for Oxygen Reduction Reaction

We investigated the relationship between oxygen reduction reaction(ORR)activity and the pyrolysis temperature(650-850℃)of CuPc in alkaline solution.The highly active sites were formed through the decomposition of CuPc or Cu-N_(4) structure after releasing 4-nitrophthalonitrile.Cu-Nx incorporated with carbon were the main active sites.The XPS measurement results show that,at lower temperature,the contents of pyridinic-N and pyrrolic-N account for the most of the total N.As the temperature is higher than 750℃,the content of graphitic N(26.11%)increases and pyridinic-N(58.81%)becomes the dominant specie.When the temperature is higher than 850℃,the content of graphitic N increases remarkably and becomes the dominant species.Moreover,the specific surface areas decrease with increased pyrolysis temperature.Benefiting from the synergistic effect,the pyrolysis temperature at 750℃of CuPc displays superior electrocatalytic properties.The obtained results reveal that the fabricated non-noble metal catalysts can be used as low-cost,efficient catalyst for water splitting ORR in metal-air batteries and fuel cells.

OsMYB84,a transcriptional regulator of OsCOPT2 and OsHMA5,modulates copper uptake and transport and yield production in rice

Transcription factors regulating crop uptake and translocation of the micronutrient Cu have not been identified.We isolated a novel R2R3-MYB transcription factor,OsMYB84,and showed that it was a positive regulator involved in uptake and transport of Cu via activation of OsCOPT2 and OsHMA expression.OsMYB84 was highly expressed in roots and anthers and induced by Cu.Overexpression of OsMYB84 promoted uptake and root-to-shoot translocation of Cu in rice,facilitated Cu distribution into grain and increased grain yield.In contrast,mutation of OsMYB84 reduced Cu concentration in xylem sap.OsMYB84 bound to the promoter region of OsCOPT2 and OsHMA5 and upregulated their expression.OsCOPT2 mutants showed reduced uptake of Cu and OsHMA5 overexpression lines showed increased root-to-shoot translocation of Cu.

Purification of copper foils driven by single crystallization

High-purity copper(Cu) with excellent thermal and electrical conductivity, is crucial in modern technological applications, including heat exchangers, integrated circuits, and superconducting magnets. The current purification process is mainly based on the zone/electrolytic refining or anion exchange, however, which excessively relies on specific integrated equipment with ultra-high vacuum or chemical solution environment, and is also bothered by external contaminants and energy consumption. Here we report a simple approach to purify the Cu foils from 99.9%(3N) to 99.99%(4N) by a temperature-gradient thermal annealing technique, accompanied by the kinetic evolution of single crystallization of Cu.The success of purification mainly relies on(i) the segregation of elements with low effective distribution coefficient driven by grain-boundary movements and(ii) the high-temperature evaporation of elements with high saturated vapor pressure.The purified Cu foils display higher flexibility(elongation of 70%) and electrical conductivity(104% IACS) than that of the original commercial rolled Cu foils(elongation of 10%, electrical conductivity of ~ 100% IACS). Our results provide an effective strategy to optimize the as-produced metal medium, and therefore will facilitate the potential applications of Cu foils in precision electronic products and high-frequency printed circuit boards.

Copper slag assisted coke reduction of phosphogypsum for sulphur dioxide preparation

The reduction of phosphogypsum(PG)to lime slag and SO_(2)using coke can effectively alleviate the environmental problems caused by PG.However,the PG decomposition temperature remains high and the product yield remains poor.By adding additives,the decomposition temperature can be further reduced and PG decomposition rate and product yield can be improved.However,the use of current additives such as Fe_(2)O_(3)and SiO_(2)brings the problem of increasing economic cost.Therefore,it is proposed to use solid waste copper slag(CS)as a new additive to reduce PG to prepare SO2,which can reduce the cost and meet the environmental benefits at the same time.The effects of proportion,temperature and thermostatic time on PG decomposition are investigated by experimental and kinetic analysis combined with FactSage thermodynamic calculations to optimize the roasting conditions.Finally,the reaction mechanism is proposed.It is found that adding CS to the coke and PG system can increase the rate of PG decomposition and SO_(2)yield while lowering the PG decomposition temperature.For example,when the CS/PG mass ratio increases from 0 to 1,PG decomposition rate increases from 83.38%to 99.35%,SO_(2)yield increases from 78.62%to 96.81%,and PG decomposition temperature decreases from 992.4℃to 949.6℃.The optimal reaction parameters are CS/PG mass ratio of 1,Coke/PG mass ratio of 0.06 at 1100℃for 20 min with 99.35%PG decomposition rate and 96.81%SO_(2) yield.The process proceeds according to the following reactions:2CaSO_(4)+ 0.7C + 0.8Fe_(2)SiO_(4)→0.8Ca_(2)SiO_(4)+ 0.2Ca_(2)Fe_(2)O_(5)+ 0.4Fe_(3)O_(4)+2SO_(2)+ 0.7CO_(2)Finally,a process for decomposing PG with coke and CS is proposed.

A Multi-Stage Differential-Multifactorial Evolutionary Algorithm for Ingredient Optimization in the Copper Industry

Ingredient optimization plays a pivotal role in the copper industry,for which it is closely related to the concentrate utilization rate,stability of furnace conditions,and the quality of copper production.To acquire a practical ingredient plan,which should exhibit long duration time with sufficient utilization and feeding stability for real applications,an ingredient plan optimization model is proposed in this study to effectively guarantee continuous production and stable furnace conditions.To address the complex challenges posed by this integer programming model,including multiple coupling feeding stages,intricate constraints,and significant non-linearity,a multi-stage differential-multifactorial evolution algorithm is developed.In the proposed algorithm,the differential evolutionary(DE)algorithm is improved in three aspects to efficiently tackle challenges when optimizing the proposed model.First,unlike traditional time-consuming serial approaches,the multifactorial evolutionary algorithm is utilized to optimize multiple complex models contained in the population of evolutionary algorithm caused by the feeding stability in a parallel manner.Second,a repair algorithm is employed to adjust infeasible ingredient lists in a timely manner.In addition,a local search strategy taking feedback from the current optima and considering the different positions of global optimum is developed to avoiding premature convergence of the differential evolutionary algorithm.Finally,the simulation experiments considering different planning horizons using real data from the copper industry in China are conducted,which demonstrates the superiority of the proposed method on feeding duration and stability compared with other commonly deployed approaches.It is practically helpful for reducing material cost as well as increasing production profit for the copper industry.

Breaking the Fe_(3)O_(4)-wrapped copper microstructure to enhance copper-slag separation

The precipitation of Fe_(3)O_(4)particles and the accompanied formation of Fe_(3)O_(4)-wrapped copper structure are the main obstacles to copper recovery from the molten slag during the pyrometallurgical smelting of copper concentrates.Herein,the commercial powdery pyrite or anthracite is replaced with pyrite-anthracite pellets as the reductants to remove a large amount of Fe_(3)O_(4)particles in the molten slag,resulting in a deep fracture in the Fe_(3)O_(4)-wrapped copper microstructure and the full exposure of the copper matte cores.When 1wt%composite pellet is used as the reductant,the copper matte droplets are enlarged greatly from 25μm to a size observable by the naked eye,with the copper content being enriched remarkably from 1.2wt%to 4.5wt%.Density functional theory calculation results imply that the formation of the Fe_(3)O_(4)-wrapped copper structure is due to the preferential adhesion of Cu_(2)S on the Fe_(3)O_(4)particles.X-ray photoelectron spectroscopy,Fourier transform infrared spectrometer(FTIR),and Raman spectroscopy results all reveal that the high-efficiency conver-sion of Fe_(3)O_(4)to FeO can decrease the volume fraction of the solid phase and promote the depolymerization of silicate network structure.As a consequence,the settling of copper matte droplets is enhanced due to the lowered slag viscosity,contributing to the high efficiency of copper-slag separation for copper recovery.The results provide new insights into the enhanced in-situ enrichment of copper from mol-ten slag.

ZNT1 Involves Cuproptosis through Regulating MTF1-conduced Expression of MT1X under Copper Overload

Industrial activities such as smelting emissions,mineral combustion and industrial wastewater discharge might lead to copper pollution in the environment.This kind of copper pollution has harmful effects on aquatic o rganisms,plants and animals through direct or indirect exposure.However,the current understanding of the toxicity of copper is rather limited.Copper overload can perturb intracellular homeostasis and induce oxidative stress and e ven cell death.Recently,cuproptosis has been identified as a copper-dependent form of cell death induced by o xidative stress in mitochondria.We uncover here that zinc transporter 1(ZNT1)is an important regulator involved in cuproptosis.Firstly,we established the copper overload-induced cell death model with the overexpression of copper importer SLC31A1 in HeLa cells.Using this model,we conducted unbiased genome-wide CRISPR-Cas9 screens in cells treated with copper.Our results revealed a significant enrichment of ZNT1 gene in both library A and library B plasmids.Knocking out of ZNT1 in HeLa cells notably prevented cuproptosis.Subsequent knockout of metal transcription factor 1(MTF1)in ZNT1-deficient cells nearly abolished their ability to resist copper-induced cell death.However,overexpression of metallothionein 1X(MT1X)in the double-knockout cells could p artially restored the resistance to cuproptosis by loss of MTF1.Mechanistically,knockout of ZNT1 could promote MT1X expression by activating MTF1.As a consequence,the interaction between MT1X and copper was e nhanced,reducing the flow of copper into mitochondria and eliminating mitochondria damage.Taken together,this study reveals the important role of ZNT1 in cuproptosis and shows MTF1-MT1X axis mediated resistance to c uproptosis.Moreover,our study will help to understand the regulatory mechanism of cellular and systemic copper homeostasis under copper overload,and present insights into novel treatments for damages caused by both genetic copper overload diseases and environmental copper contamination.