Copper homeostasis and neurodegenerative diseases

Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and COX17.Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue.Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative disorders.However,the exact mechanisms underlying these processes are not known.Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress.Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction.Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory pathways.Additionally,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell death.This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis.By synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders,such as Wilson's disease,Menkes'disease,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,and multiple sclerosis.Potential clinically significant therapeutic targets,including superoxide dismutase 1,D-penicillamine,and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline,along with their associated therapeutic agents,are further discussed.Ultimately,we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.

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.

Metabolomic Changes in Mice Induced by Copper Exposure:Systematic Analysis and Exploration of Toxicity Mechanisms

Copper is one of the essential trace elements for living beings,influencing several critical processes like cellular energy production,antioxidant defense,communication within cells,and the functioning of enzymes[1].The daily intake of copper is 0.7−3.0 mg/d,and copper homeostasis is strictly regulated by physiological processes,including duodenal and small intestinal uptake,blood transport,liver storage and release,and bile excretion,thereby maintaining copper homeostasis in the body[2],and many studies have confirmed that copper disorders in the body are associated with neurodegenerative,metabolic,and genetic diseases[3].

2024 Annual Report of China Mineral Resources (copper, gold, coal, etc.)

In October 2024,the Ministry of Natural Resources of PRC released the 2024 China Mineral Resources Report,which focuses on new progress since 2023 in the geological and mineral survey and evaluation,mineral resource exploration and development,mine ecological restoration,green mine construction,new changes in mineral resource policies and regulations,new measures in mineral resource management,new situations in scientific and technological innovation,as well as the new achievements of the international geological and mineral cooperation.

Numerical Simulation of Flow and Temperature Distribution in a Bottom-Blown Copper Bath

Smelting with oxygen bottom blowing is one of the main methods used in the frame of copper pyrometallurgy.With this approach,feed materials and oxygen-enriched air are introduced in reversed order to enhance multiphaseflow within the furnace.Understanding the flow structure and temperature distribution in this setup is crucial foroptimizing production.In this study,gas-liquid interactions,and temperature profiles under varying air-injectionconditions are examined by means of numerical simulation for a 3.2 m×20 m furnace.The results indicate that thehigh-velocity regions are essentially distributed near the lance within the reaction region and the flue gas outlet,while low-velocity regions are located close to the furnace walls on both side of the reaction region.Dead regionsappear in the sedimentation region,with gas velocities surpassing those of the molten phase.As the injection rateincreases from 0.50 to 0.80 Nm3/s,the stabilization time of the average liquid surface velocity decreases from 2.6 sto 1.9 s,exhibiting a similar trend to the gas holdup.During stabilization,the average liquid surface velocity risesfrom 0.505 to 0.702 m/s.The average turbulent kinetic energy(TKE)of the fluid in the molten bath increases from0.095 to 0.162 m^(2)/s^(2).The proportion of the area distribution with TKE greater than 0.10 m^(2)/s^(2) and the gas holdupat steady state both rise with an increase in the injection quantity.The maximum splashing height of the melt growsfrom approximately 0.756 to 1.154 m,with the affected area expanding from 14.239 to 20.498 m^(2).Under differentworking conditions with varying injection quantities,the average temperature changes in melt zone and flue gaszone of the furnace are small.The temperature in the melt and in the flue-gas zone spans the interval 1200℃–1257℃,and 1073℃–1121℃,respectively.The temperature distribution of the melt and flue gas reveals a patterncharacterized by elevated temperatures in the reaction zone,gradually transitioning to lower temperatures in thesedimentation region.

Numerical Simulation of Blood Flow Dynamics in a Stenosed Artery Enhanced by Copper and Alumina Nanoparticles

Nanotechnology holds immense importance in the biomedical field due to its ability to revolutionize healthcare on a molecular scale.Motivated by the imperative of enhancing patient outcomes,a comprehensive numerical simulation study on the dynamics of blood flow in a stenosed artery,focusing on the effects of copper and alumina nanoparticles,is conducted.The study employs a 2-dimensional Newtonian blood flow model infused with copper and alumina nanoparticles,considering the influence of a magnetic field,thermal radiation,and various flow parameters.The governing differential equations are first non-dimensionalized to facilitate analysis and subsequently solved using the 4th order collocation method,bvp4c module in MATLAB.This approach obtains velocity and temperature profiles,revealing the impact of relevant parameters crucial in the biomedical field.The findings of this study underscore the significance of understanding blood flow dynamics in stenosed arteries and the potential benefits of utilizing copper and alumina nanoparticles in treatment strategies.The incorporation of nanoparticles introduces novel avenues for enhancing therapeutic interventions,particularly in mitigating the effects of stenosis.The elucidation of velocity and temperature profiles provides valuable insights into the behavior of blood flow under different conditions,thereby informing the development of targeted biomedical applications.The arterial curvature flow parameter influences temperature profiles,with increased parameters promoting more efficient heat dissipation.The elevated values of Prandtl number and thermal radiation parameter showcase the diminished temperature profiles,indicating stronger dominance of momentum diffusion over thermal diffusion and radiative heat transfer mechanism.Sensitivity analysis of the pertinent physical parameters reveals that the Prandtl number has the most significant impact on blood flow dynamics.A statistical analysis of the present results and existing literature has also been included in the study.Overall,this research contributes to advancing our understanding of vascular health and lays the groundwork for innovative approaches in stenosis treatment and related biomedical fields.

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.

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.

One stone two birds:electrochemical and colorimetric dual-mode biosensor based on copper peroxide/covalent organic framework nanocomposite for ultrasensentive norovirus detection

Norovirus(NoV)is regarded as one of the most common causes of foodborne diarrhea in the world.It is urgent to identify the pathogenic microorganism of the diarrhea in short time.In this work,we developed an electrochemical and colorimetric dual-mode detection for NoV based on the excellent dual catalytic properties of copper peroxide/COF-NH_(2)nanocomposite(CuO_(2)@COF-NH_(2)).For the colorimetric detection,NoV can be directly detected by the naked eye based on CuO_(2)@COF-NH_(2)as a laccase-like nonazyme using“peptide-NoV-antibody”recognition mode.The colorimetric assay displayed a wide and quality linear detection range from 1 copy/mL to 5000 copies/mL of NoV with a low limit of detection(LOD)of 0.125 copy/mL.For the electrochemical detection of NoV,CuO_(2)@COF-NH_(2)showed an oxidation peak of copper ion from Cu^(+)to Cu^(2+)using“peptide-NoV-antibody”recognition mode.The electrochemical assay showed a linear detection range was 1-5000 copies/mL with a LOD of 0.152 copy/mL.It's worthy to note that this assay does not need other electrical signal molecule,which provide the stable and sensitive electrochemial detection for NoV.The electrochemical and colorimetric dual-mode detection was used to detect NoV in foods and faceal samples,which has the potential for improving food safety and diagnosing of NoV-infected diarrhea.

An in-situ hybrid laser-induced integrated sensor system with antioxidative copper

Integration of sensors with engineering thermoplastics allows to track their health and surrounding stimuli.As one of vital backbones to construct sensor systems,copper(Cu)is highly conductive and cost-effective,yet tends to easily oxidize during and after processing.Herein,an in-situ integrated sensor system on engineering thermoplastics via hybrid laser direct writing is proposed,which primarily consists of laser-passivated functional Cu interconnects and laser-induced carbon-based sensors.Through a one-step photothermal treatment,the resulting functional Cu interconnects after reductive sintering and passivation are capable of resisting long-term oxidation failure at high temperatures(up to 170℃)without additional encapsulations.Interfacing with signal processing units,such an all-in-one system is applied for long-term and real-time temperature monitoring.This integrated sensor system with facile laser manufacturing strategies holds potentials for health monitoring and fault diagnosis of advanced equipment such as aircrafts,automobiles,high-speed trains,and medical devices.

Additive manufacturing of pure copper via vat photopolymerization with slurry

Stereolithography(SLA)combined with a two-step post-processing method“oxidation−reduction”was developed to fabricate pure copper with high complexity.The copper slurries for SLA were prepared,and particularly the influence of volume fraction of copper on the properties of copper slurries was investigated.In the two-step post-treatment process,organics were removed by oxidation and copper powder was oxidized simultaneously,and then the oxidized copper was reduced into highly reactive copper particles,improving the sintering activity of the copper green body and enhancing the relative density of the sintered part.The results show that curing depth of the copper slurries decreased with the increase of volume fraction of copper.The viscosity of the pure copper slurry rises exponentially as the volume fraction of copper exceeded 50%.The highest volume fraction of pure copper slurry for SLA is 55%.The specimens exhibited an increase in hardness and electrical conductivity with the increase of volume fraction of copper.Specifically,the maximum values of hardness and conductivity of samples with 55 vol.%copper were HV 52.7 and 57.1%(IACS),respectively.

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.

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.

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.

Using Electrodeposition of Carboxylated Chitosan for Green Preparation of Copper Nanoclusters and Nanocomposite Films

On the basis of coordinated electrodeposition of carboxylated chitosan(CCS),we presented a green method to prepare Cu NCs and Cu NCs/CCS nanocomposite films.The method shows a range of benefits,such as the convenient and eco-friendly process,mild conditions,and simple post-treatment.The experimental results reveal that a homogeneous deposited film(Cu NCs/CCS nanocomposite film)is generated on the Cu plate(the anode)after electrodeposition,which exhibits an obvious red florescence.The results from TEM observation suggest there are nanoparticles(with the average particle size of 2.3 nm)in the deposited film.Spectral analysis results both demonstrate the existence of Cu NCs in the deposited film.Moreover,the Cu NCs/CCS film modified electrode is directly created through electrodeposition of CCS,which enables promising application in the electrochemical sensing.By means of fluorescence properties of Cu NCs,the Cu NCs/CCS film also owns the potential in fluorescence detection.Therefore,this work builds a novel method for the green synthesis of Cu NCs,meanwhile it offers a convenient and new electrodeposition strategy to prepare polysaccharide-based Cu NCs nanocomposites for uses in functional nanocomposites and bioelectronic devices.

pH-responsive corrosion protection of chitosan-coated hollow mesoporous silica microspheres loaded with 2-mercaptobenzothiazole coating on copper substrates

An active protection coating for pH-responsive was prepared.The hollow mesoporous silica microspheres(HMSNs)were loaded with 2-mercaptobenzothiazole(MBT),and then they were coated with chitosan(CS).The composite microspheres were in the range of 650−750 nm in diameter.CS-HMSN-MBT coating had a faster repair rate under acidic conditions by synergistic effect between CS and MBT.The repair rate under alkaline conditions was slowed down.The active protection performance reached the strongest after 3 d immersion.The corrosion inhibitor release mechanism was optimized to extend the service life of the coating and to achieve long-term service of the copper substrate.

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.