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.

Single-atom catalysts for the electrochemical reduction of carbon dioxide into hydrocarbons and oxygenates

The electrochemical reduction of carbon dioxide offers a sound and economically viable technology for the electrification and decarbonization of the chemical and fuel industries.In this technology,an electrocatalytic material and renewable energy-generated electricity drive the conversion of carbon dioxide into high-value chemicals and carbon-neutral fuels.Over the past few years,single-atom catalysts have been intensively studied as they could provide near-unity atom utilization and unique catalytic performance.Single-atom catalysts have become one of the state-of-the-art catalyst materials for the electrochemical reduction of carbon dioxide into carbon monoxide.However,it remains a challenge for single-atom catalysts to facilitate the efficient conversion of carbon dioxide into products beyond carbon monoxide.In this review,we summarize and present important findings and critical insights from studies on the electrochemical carbon dioxide reduction reaction into hydrocarbons and oxygenates using single-atom catalysts.It is hoped that this review gives a thorough recapitulation and analysis of the science behind the catalysis of carbon dioxide into more reduced products through singleatom catalysts so that it can be a guide for future research and development on catalysts with industry-ready performance for the electrochemical reduction of carbon dioxide into high-value chemicals and carbon-neutral fuels.

p-d Orbital Hybridization Engineered Single-Atom Catalyst for Electrocatalytic Ammonia Synthesis

The rational design of metal single-atom catalysts(SACs)for electrochemical nitrogen reduction reaction(NRR)is challenging.Two-dimensional metal-organic frameworks(2DMOFs)is a unique class of promising SACs.Up to now,the roles of individual metals,coordination atoms,and their synergy effect on the electroanalytic performance remain unclear.Therefore,in this work,a series of 2DMOFs with different metals and coordinating atoms are systematically investigated as electrocatalysts for ammonia synthesis using density functional theory calculations.For a specific metal,a proper metal-intermediate atoms p-d orbital hybridization interaction strength is found to be a key indicator for their NRR catalytic activities.The hybridization interaction strength can be quantitatively described with the p-/d-band center energy difference(Δd-p),which is found to be a sufficient descriptor for both the p-d hybridization strength and the NRR performance.The maximum free energy change(ΔG_(max))andΔd-p have a volcanic relationship with OsC_(4)(Se)_(4)located at the apex of the volcanic curve,showing the best NRR performance.The asymmetrical coordination environment could regulate the band structure subtly in terms of band overlap and positions.This work may shed new light on the application of orbital engineering in electrocatalytic NRR activity and especially promotes the rational design for SACs.

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.

Rational design of MXene-based vacancy-confined single-atom catalyst for efficient oxygen evolution reaction

Two-dimensional transition metal carbides(MXenes) have been demonstrated to be promising supports for single-atom catalysts(SACs) to enable efficient oxygen evolution reaction(OER).However,the rational design of MXene-based SACs depends on an experimental trial-and-error approach.A theoretical guidance principle is highly expected for the efficient evaluation of MXene-based SACs.Herein,highthroughput screening was performed through first-principles calculations and machine learning techniques.Ti_(3)C_(2)(OH)_(x),V_(3)C_(2)(OH)_(x),Zr_(3)C_(2)(OH)_(x),Nb_(3)C_(2)(OH)_(x),Hf_(3)C_(2)(OH)_(x),Ta_(3)C_(2)(OH)_(x),and W_(3)C_(2)(OH)_(x) were screened out based on their excellent stability.Zn,Pd,Ag,Cd,Au,and Hg were proposed to be promising single atoms anchored in MXenes based on cohesive energy analysis.Hf_(3)C_(2)(OH)_(x) with a Pd single atom delivers a theoretical overpotential of 81 mV.Both moderate electron-deficient state and high covalency of metal-carbon bonds were critical features for the high OER reactivity.This principle is expected to be a promising approach to the rational design of OER catalysts for metal-air batteries,fuel cells,and other OER-based energy storage devices.

Two-dimensional C_(2)N-based single-atom catalyst with complex microenvironment for enhanced electrochemical nitrogen reduction:A descriptor-based design

The catalytic descriptor with operational feasibility is highly desired towards rational design of high-performance catalyst especially the electrode/electrolyte solution interface working under mild conditions.Herein,we demonstrate that the descriptorΩparameterized by readily accessible intrinsic properties of metal center and coordination is highly operational and efficient in rational design of single-atom catalyst(SAC)for driving electrochemical nitrogen reduction(NRR).Using twodimensional metal(M)-B_(x)P_(y)S_(z)N_m@C_(2)N as prototype SAC models,we reveal that^(*)N_(2)+(H~++e~-)→^(*)N_(2)H acts predominantly as the potential-limiting step(PLS)of NRR on M-B_(2)P_(2)S_(2)@C_(2)N and M-B_(1)P_(1)S_(1)N_(3)@C_(2)N regardless of the distinction in coordination microenvironment.Among the 28 screened M active sites,withΩvalues close to the optimal 4,M-B_(2)P_(2)S_(2)@C_(2)N(M=V(Ω=3.53),Mo(Ω=5.12),and W(Ω=3.92))and M-B_(1)P_(1)S_(1)N_(3)@C_(2)N(M=V(Ω=3.00),Mo(Ω=4.34),and W(Ω=3.32))yield the lowered limiting potential(U_(L))as-0.45,-0.54.-0.36,-0.58,-0.25,and-0.24 V,respectively,thus making them the promising NRR catalysts.More importantly,these SACs are located around the top of volcano-shape plot of U_(L) versusΩ,re-validatingΩas an effective descriptor for accurately predicting the high-activity NRR SACs even with complex coordination.Our study unravels the relationship between active-site structure and NRR performance via the descriptorΩ,which can be applied to other important sustainable electrocatalytic reactions involving activation of small molecules viaσ-donation andπ^(*)-backdonation mechanism.

Cu single-atom electrocatalyst on nitrogen-containing graphdiyne for CO_(2) electroreduction to CH_(4)

Developing Cu single-atom catalysts(SACs)with well-defined active sites is highly desirable for producing CH4 in the electrochemical CO_(2) reduction reaction and understanding the structure-property relationship.Herein,a new graphdiyne analogue with uniformly distributed N_(2)-bidentate(note that N_(2)-bidentate site=N^N-bidentate site;N_(2)≠dinitrogen gas in this work)sites are synthesized.Due to the strong interaction between Cu and the N_(2)-bidentate site,a Cu SAC with isolated undercoordinated Cu-N_(2) sites(Cu1.0/N_(2)-GDY)is obtained,with the Cu loading of 1.0 wt%.Cu1.0/N_(2)-GDY exhibits the highest Faradaic efficiency(FE)of 80.6% for CH_(4) in electrocatalytic reduction of CO_(2) at-0.96 V vs.RHE,and the partial current density of CH_(4) is 160 mA cm^(-2).The selectivity for CH_(4) is maintained above 70% when the total current density is 100 to 300 mA cm^(-2).More remarkably,the Cu1.0/N_(2)-GDY achieves a mass activity of 53.2 A/mgCu toward CH4 under-1.18 V vs.RHE.In situ electrochemical spectroscopic studies reveal that undercoordinated Cu-N_(2) sites are more favorable in generating key ^(*)COOH and ^(*)CHO intermediate than Cu nanoparticle counterparts.This work provides an effective pathway to produce SACs with undercoordinated Metal-N_(2) sites toward efficient electrocatalysis.

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.

Boric Acid-Assisted Pyrolysis for High-Loading Single-Atom Catalysts to Boost Oxygen Reduction Reaction in Zn-Air Batteries

The emerging of single-atom catalysts(SACs)offers a great opportunity for the development of advanced energy storage and conversion devices due to their excellent activity and durability,but the actual mass production of high-loading SACs is still challenging.Herein,a facile and green boron acid(H_(3)BO_(3))-assisted pyrolysis strategy is put forward to synthesize SACs by only using chitosan,cobalt salt and H_(3)BO_(3)as precursor,and the effect of H_(3)BO_(3)is deeply investigated.The results show that molten boron oxide derived from H_(3)BO_(3)as ideal high-temperature carbonization media and blocking media play important role in the synthesis process.As a result,the acquired Co/N/B tri-doped porous carbon framework(Co-N-B-C)not only presents hierarchical porous structure,large specific surface area and abundant carbon edges but also possesses high-loading single Co atom(4.2 wt.%),thus giving rise to outstanding oxygen catalytic performance.When employed as a catalyst for air cathode in Zn-air batteries,the resultant Co-N-B-C catalyst shows remarkable power density and long-term stability.Clearly,our work gains deep insight into the role of H_(3)BO_(3)and provides a new avenue to synthesis of high-performance SACs.

Biomass-derived porous carbon with single-atomic cobalt toward high-performance aqueous zinc-sulfur batteries at room temperature

Aqueous zinc-sulfur batteries at room temperature hold great potential for next-generation energy storage technology due to their low cost,safety and high energy density.However,slow reaction kinetics and high activation energy at the sulfur cathode pose great challenges for the practical applications.Herein,biomass-derived carbon with single-atomic cobalt sites(MMPC-Co)is synthesized as the cathode in Zn-S batteries.The catalysis of single-atom Co sites greatly promotes the transform of cathode electrolyte interface(CEI)on the cathode surface,while offering accelerated charge transfer rate for high conversion reversibility and large electrochemical surface area(ECSA)for high electrocatalytic current.Furthermore,the rich pore structure not only physically limits sulfur loss,but also accelerates the transport of zinc ions.In addition,the large pore volume of MMPC-Co is able to relieve the stress effect caused by the volume expansion of Zn S during charge/discharge cycles,thereby maintaining the stability of electrode structure.Consequently,the sulfur cathode maintains a high specific capacity of 729.96 m A h g^(-1)after 500 cycles at4 A g^(-1),which is much better than most cathode materials reported in the literature.This work provides new insights into the design and development of room-temperature aqueous Zn-S batteries.

Insight into demand-driven preparation of single-atomic mediators for lithium–sulfur batteries

Lithium-sulfur(Li-S) batteries have attracted considerable attention as one of the most appealing energy storage systems.Strenuous efforts have been devoted to tackling the tremendous challenges,mainly pertaining to the severe shuttle effect,sluggish redox kinetics and lithium dendritic growth.Single-atomic mediators as promising candidates exhibit impressive performance in addressing these intractable issues.Related research often utilizes a trial-and-error approach,proposing solutions to fabricate single-atomic materials with diversified features.However,comprehensive review articles especially targeting demand-driven preparation are still in a nascent stage.Inspired by these considerations,this review summarizes the design of single-atomic mediators based on the application case-studies in LiS batteries and other metal-sulfur systems.Emerging preparation routes represented by chemical vapor deposition technology are introduced in a demand-oriented classification.Finally,future research directions are proposed to foster the advancement of single-atomic mediators in Li-S realm.

Structural engineering of Fe single-atom oxygen reduction catalyst with high site density and improved mass transfer

Fe-N-C catalysts are widely considered as promising non-precious-metal candidates for electrocatalytic oxygen reduction reaction(ORR),Yet despite their high catalytic activity through rational modulation,challenges remain in their low site density and unsatisfactory mass transfer structure.Herein,we present a structural engineering approach employing a soft-template coating strategy to fabricate a hollow and hierarchically porous N-doped carbon framework anchored with atomically dispersed Fe sites(FeNCh) as an efficient ORR catalyst.The combination of hierarchical porosity and high exterior surface area is proven crucial for exposing more active sites,which gives rise to a remarkable ORR performance with a half-wave potential of 0.902 V in 0.1 m KOH and 0.814 V in 0.1 m HClO_(4),significantly outperforming its counterpart with solid structure and dominance of micropores(FeNC-s).The mass transfer property is revealed by in-situ electrochemical impedance spectroscopy(EIS) measurement.The distribution of relaxation time(DRT) analysis is further introduced to deconvolve the kinetic and mass transport processes,which demonstrates an alleviated mass transport resistance for FeNC-h,validating the effectiveness of structural engineering.This work not only provides an effective structural engineering approach but also contributes to the comprehensive mass transfer evaluation on advanced electrocatalyst for energy conversion applications.

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.

Single-atom modified graphene cocatalyst for enhanced photocatalytic CO_(2) reduction on halide perovskite

Metal halide perovskite(MHP)has become one of the most promising materials for photocatalytic CO_(2) reduction owing to the wide light absorption range,negative conduction band position and high reduction ability.However,photoreduction of CO_(2) by MHP remains a challenge because of the slow charge separation and transfer.Herein,a cobalt single-atom modified nitrogen-doped graphene(Co-NG)cocatalyst is prepared for enhanced photocatalytic CO_(2) reduction of bismuth-based MHP Cs_(3)Bi_(2)Br_(9).The optimal Cs_(3)Bi_(2)Br_(9)/Co-NG composite exhibits the CO production rate of 123.16μmol g^(-1)h^(-1),which is 17.3 times higher than that of Cs_(3)Bi_(2)Br_(9).Moreover,the Cs_(3)Bi_(2)Br_(9)/Co-NG composite photocatalyst exhibits nearly 100% CO selectivity as well as impressive long-term stability.Charge carrier dynamic characterizations such as Kelvin probe force microscopy(KPFM),single-particle PL microscope and transient absorption(TA)spectroscopy demonstrate the vital role of Co-NG cocatalyst in accelerating the transfer and separation of photogenerated charges and improving photocatalytic performance.The reaction mechanism has been demonstrated by in situ diffuse reflectance infrared Fourier-transform spectroscopy measurement.In addition,in situ X-ray photoelectron spectroscopy test and theoretical calculation reveal the reaction reactive sites and reaction energy barriers,demonstrating that the introduction of Co-NG promotes the formation of ^(*)COOH intermediate,providing sufficient evidence for the highly selective generation of CO.This work provides an effective single-atom-based cocatalyst modification strategy for photocatalytic CO_(2) reduction and is expected to shed light on other photocatalytic applications.

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.

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.

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.