Ferroptosis and endoplasmic reticulum stress in ischemic stroke

Ferroptosis is a form of non-apoptotic programmed cell death,and its mechanisms mainly involve the accumulation of lipid peroxides,imbalance in the amino acid antioxidant system,and disordered iron metabolism.The primary organelle responsible for coordinating external challenges and internal cell demands is the endoplasmic reticulum,and the progression of inflammatory diseases can trigger endoplasmic reticulum stress.Evidence has suggested that ferroptosis may share pathways or interact with endoplasmic reticulum stress in many diseases and plays a role in cell survival.Ferroptosis and endoplasmic reticulum stress may occur after ischemic stroke.However,there are few reports on the interactions of ferroptosis and endoplasmic reticulum stress with ischemic stroke.This review summarized the recent research on the relationships between ferroptosis and endoplasmic reticulum stress and ischemic stroke,aiming to provide a reference for developing treatments for ischemic stroke.

Ferroptosis mechanism and Alzheimer's disease

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.

High-rate electrochemical H_(2)O_(2) production over multimetallic atom catalysts under acidic–neutral conditions

Hydrogen peroxide(H_(2)O_(2))production by the electrochemical 2-electron oxygen reduction reaction(2e−ORR)is a promising alternative to the energy-intensive anthraquinone process,and single-atom electrocatalysts show the unique capability of high selectivity toward 2e−ORR against the 4e−one.The extremely low surface density of the single-atom sites and the inflexibility in manipulating their geometric/electronic configurations,however,compromise the H_(2)O_(2) yield and impede further performance enhancement.Herein,we construct a family of multiatom catalysts(MACs),on which two or three single atoms are closely coordinated to form high-density active sites that are versatile in their atomic configurations for optimal adsorption of essential*OOH species.Among them,the Cox–Ni MAC presents excellent electrocatalytic performance for 2e−ORR,in terms of its exceptionally high H_(2)O_(2) yield in acidic electrolytes(28.96 mol L^(−1) gcat.^(−1) h^(−1))and high selectivity under acidic to neutral conditions in a wide potential region(>80%,0–0.7 V).Operando X-ray absorption and density functional theory analyses jointly unveil its unique trimetallic Co2NiN8 configuration,which efficiently induces an appropriate Ni–d orbital filling and modulates the*OOH adsorption,together boosting the electrocatalytic 2e−ORR capability.This work thus provides a new MAC strategy for tuning the geometric/electronic structure of active sites for 2e−ORR and other potential electrochemical processes.

Metformin alleviates spinal cord injury by inhibiting nerve cell ferroptosis through upregulation of heme oxygenase-1 expression

Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox homeostasis.Metformin is a classic drug used to treat type 2 diabetes that can inhibit ferroptosis.Previous studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 expression.Therefore,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord injury.To test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord injury.Next,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell ferroptosis.Continuous intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord injury.Subsequently,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord injury.Taken together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.

Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence and development of primary liver cancer

As a highly aggressive tumor,the pathophysiological mechanism of primary liver cancer has attracted much attention.In recent years,factors such as ferroptosis regulation,lipid peroxidation and metabolic abnormalities have emerged in the study of liver cancer,providing a new perspective for understanding the development of liver cancer.Ferroptosis regulation,lipid peroxidation and metabolic abnormalities play important roles in the occurrence and development of liver cancer.The regulation of ferroptosis is involved in apoptosis and necrosis,affecting cell survival and death.Lipid peroxidation promotes oxidative damage and promotes the invasion of liver cancer cells.Metabolic abnormalities,especially the disorders of glucose and lipid metabolism,directly affect the proliferation and growth of liver cancer cells.Studies of ferroptosis regulation and lipid peroxidation may help to discover new therapeutic targets and improve therapeutic outcomes.The understanding of metabolic abnormalities can provide new ideas for the prevention of liver cancer,and reduce the risk of disease by adjusting the metabolic process.This review focuses on the key roles of ferroptosis regulation,lipid peroxidation and metabolic abnormalities in this process.

Hydrometallurgical processing of chalcopyrite:A review of leaching techniques

Copper,an essential metal for the energy transition,is primarily obtained from chalcopyrite through hydrometallurgical and pyrometallurgical methods.The risks and harmful impacts of these processes pose significant concerns for environmental and human safety,highlighting the need for more efficient and eco-friendly hydrometallurgical methods.This review article emphasizes current pro-cesses such as oxidative leaching,bioleaching,and pressure leaching that have demonstrated efficiency in overcoming the complicated chalcopyrite network.Oxidative leaching operates under benign conditions within the leaching media;nevertheless,the introduction of oxidizing agents provides benefits and advantages.Bioleaching,a non-aggressive method,has shown a gradual increase in copper extrac-tion efficiency and has been explored using both primary and secondary sources.Pressure leaching,known for its effectiveness and se-lectivity in copper extraction,is becoming commercially more viable with increased research investments.This research also provides im-portant data for advancing future research in the field.

Mechanisms and active substances of targeting lipid peroxidation in ferroptosis regulation

Ferroptosis is a novel form of cell death driven by iron-dependent lipid peroxidation and it is implicated in various diseases,such as liver disease,acute kidney injury,cardiovascular disease,neurodegenerative disease and cancer.Lipid-based reactive oxygen species(ROS),particularly lipid hydroperoxides in the cellular membrane can lead to membrane disruption and cell death mediated by ferroptosis.There are three necessary stages involving in the process of lipid peroxidation regulation in ferroptosis,including the synthesis of membrane phospholipids,initiation of lipid peroxidation and clearance of lipid peroxides.In this review,we summarized the molecular modulation mechanisms of lipid peroxidation in ferroptosis from the above three stages,as well as various ferroptosis modulators targeting lipid peroxidation,including commonly used products,natural bioactive compounds and selenocompounds.Collectively,these findings suggest the vital role of lipid peroxidation in ferroptosis,and targeting lipid peroxidation in ferroptosis is potential to treat ferroptosis-associated diseases.

New insights on the role of chondroitin sulfate proteoglycans in neural stem cell–mediated repair in spinal cord injury

Extensive neurodegeneration is a hallmark of traumatic spinal cord injury (SCI) that underlies permanent sensorimotor and autonomic impairments (Alizadeh et al.,2019).Following the primary impact,the spinal cord undergoes a cascade of secondary injury mechanisms that are driven by disruption of the blood-spinal cord ba rrier,vascula r inju ry,glial reactivity,neu roinfla mmation,oxidative stress,lipid peroxidation,and glutamate excitotoxicity that culminate in neuronal and oligodendroglial cell death,demyelination,and axonal damage(Alizadeh et al.,2019).To achieve a meaningful functional recovery after SCI,regeneration of new neurons and oligodendrocytes and their successful growth and integration within the neural network are critical steps for reconstructing the damaged spinal cord tissue (Fischer et al.,2020).

Flower-like tin oxide membranes with robust three-dimensional channels for efficient removal of iron ions from hydrogen peroxide

Membrane technology has become the mainstream process for the production of electronic grade hydrogen peroxide(H_(2)O_(2)).But due to the oxidation degradation of the organic membranes(e.g.polyamide)by the strong oxidative radicals(e.g.OH)generated via the activation of H_(2)O_(2)by iron ions(Fe^(3+)),the short effective lifetime of membranes remains a challenge.Inorganic nano tin oxide(SnO_(2))has great potential for the removal of Fe^(3+)in strongly oxidative H_(2)O_(2)because of its ability to stabilize H2O_(2)and preferentially adsorb Fe^(3+).Herein,we have designed for the first time a flower-like robust SnO_(2)membrane on the ceramic support by in situ template-free one-step hydrothermal method.The three-dimensional loose pore structure in the membrane built by interlacing SnO_(2)nanosheets endows the SnO_(2)membrane with a high specific surface area and abundant adsorption sites(AOH).Based on the coordination complexation and electrostatic attraction between the SnO_(2)surface and Fe^(3+),the membrane shows a high Fe3+removal efficiency(83%)and permeability(24 L·m^(-2)·h^(-1)·MPa^(-1))in H_(2)O_(2).This study provides an innovative and simple approach to designing robust SnO_(2)membranes for highly efficient removal of Fe^(3+)in harsh environments,such as strong oxidation conditions.

Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.

Pilot Test of Preparing 2-Alkylanthraquinone Using Alkylation-Oxidation Technology

To expedite the development of industrial technology for producing 2-alkylanthraquinone,a novel pilot test of alkylation-oxidation technology was conducted.The process mainly included anthracene alkylation,separation of anthracene and 2-alkylanthracene,oxidation of 2-alkylanthracene,and product purification.Optimal alkylation conditions yielded a 91.1%conversion of anthracene and a 71.73%selectivity for 2-alkylanthracene.To address the separation problem of anthracene and 2-alkylanthracene,solvent-assisted distillation technology was developed,resulting in a 98.9%purity of 2-alkylanthracene and a 91.82%separation yield.When the molar ratio of H2O_(2) to 2-alkylanthracene was 7:1,a 98.96%conversion of 2-alkylanthracene and a 99.94%selectivity for 2-alkylanthraquinone were achieved.A novel composition of 2-alkylanthraquinone,including 2-tert-butylanthraquinone,2-tert-amylanthraquinone,and 2-hexylanthraquinone,was developed.This composition could be effectively separated and purified through a combination of crystallization and washing processes.The elemental composition of the product met the existing standards,and its hydrogenation performance closely matched that of commercially available 2-tert-amylanthraquinone products.

Suppressing a mitochondrial calcium uniporter activates the calcium signaling pathway and promotes cell elongation in cotton

Mitochondrial calcium uniporter(MCU)is a conserved calcium ion(Ca^(2+))transporter in the mitochondrial inner membrane of eukaryotic cells.How MCU proteins regulate Ca^(2+)flow and modulate plant cell development remain largely unclear.Here,we identified the gene GhMCU4 encoding a MCU protein that negatively regulates plant development and fiber elongation in cotton(Gossypium hirsutum).GhMCU4expressed constitutively in various tissues with the higher transcripts in elongating fiber cells.Knockdown of GhMCU4 in cotton significantly elevated the plant height and root length.The calcium signaling pathway was significantly activated and calcium sensor genes,including Ca^(2+)dependent modulator of interactor of constitutively active ROP(GhCMI1),calmodulin like protein(GhCML46),calciumdependent protein kinases(GhCPKs),calcineurin B-like protein(GhCBLs),and CBL-interacting protein kinases(GhCIPKs),were dramatically upregulated in GhMCU4-silenced plants.Metabolic processes were preferentially enriched,and genes related to regulation of transcription were upregulated in GhMCU4-silenced plants.The contents of Ca^(2+)and H_(2)O_(2)were significantly increased in roots and leaves of GhMCU4-silenced plants.Fiber length and Ca^(2+)and H_(2)O_(2)contents in fibers were significantly increased in GhMCU4-silenced plants.This study indicated that GhMCU4 plays a negative role in regulating cell elongation in cotton,thus expanding understanding in the role of MCU proteins in plant growth and development.

Unveiling the chemistry behind the electrolytic production of hydrogen peroxide by oxygenated carbon

Oxygenated carbon materials exhibit outstanding electrocatalytic performance in the production of hydrogen peroxide(H2O2)through a two-electron oxygen reduction reaction.The nature of the active functional group and underlying reaction mechanism,however,remain unclear.Here,a comprehensive workflow was established to identify the active sites from the numerous possible structures.The common hydroxyl group at the notched edge demonstrates a key role in the two-electron process.The local chemical environment weakens the binding of OOH intermediate to substrate while enhancing interaction with solution,thereby promoting the H_(2)O_(2)production.With increasing pH,the intramolecular hydrogen bond between OOH intermediate and hydroxyl decreases,facilitating OOH desorption.Furthermore,the rise in selectivity with increasing potential stems from the suppression of the four-electron process.The active site was further validated through experiments.Guided by theoretical understanding,optimal performance was achieved with high selectivity(>95%)and current density(2.06 mA/cm^(2))in experiment.

Identification of the highly active Zn-N_(4) sites with pyrrole/pyridine-N synergistic coordination by dz^(2)+s-band center for electrocatalytic H_(2)O_(2) production

Single metal atoms anchored on nitrogen-doped carbon materials(M-N_(4))have been identified as effective active sites for catalyzing the two-electron oxygen reduction reaction(2e-ORR).However,the relationship between the local atomic/electronic environments of the M-N_(4) sites(metal atoms coordinated with different types of N species)and their catalytic activity for 2e-ORR has rarely been elaborated clearly,which imposes significant ambiguity for the rational design of catalysts.Herein,guided by the comprehensive density-functional theory calculations and predictions,a series of Zn-N_(4) single-atom catalysts(SACs)are designed with pyrrole/pyridine-N(N_(Po)/N_(Pd))synergistic coordination and prepared by controlling the pyrolysis temperature(600,700,and 800℃),Among them,the dominated Zn-N_(4) configurations with rationally combined N_(Po)/N_(Pd)coordination show~*OOH adsorption strength close to the optimal value,much superior to those with mono N species.Thus,the as-prepared catalyst exhibits a high H_(2)O_(2) selectivity of over 90%both in neutral and alkaline environments,with a superb H_(2)O_(2) yield of up to 33.63 mol g^(-1)h^(-1)in an alkaline with flow cell.More importantly,a new descriptor,dz^(2)+s band center,has been proposed,which is especially feasible for predicting the activity for metal types with fully occupied s and d orbitals.This work thus presents clear guidance for the rational design of highly active SACs toward ORR and provides a complement to the d-band theory for more accurately predicting the catalytic activity of the materials.

Preparation of PrFe_(x)Co_(1-x)O_(3)/Mt catalyst and study on degradation of 2-hydroxybenzoic acid wastewater by catalytic wet peroxide oxidation

In this study,the perovskite nanocomposite PrFe_(x)Co_(1-x)O_(3)(Pr(S))was successfully synthesized by the sol-gel method;PrFe_(x)Co_(1-x)O_(3)/Al-pillared montmorillonite(Pr(S)/Mt)catalysts were prepared by impregnation(D)method and solid-melting(G)method,respectively,with Pr(S)as the active component and Al-pillared montmorillonite as the carrier.The catalysts were applied to treat the 2-hydroxybenzoic acid(2-HA)-simulated wastewater by catalytic wet peroxide oxidation(CWPO)technique,and the chemical oxygen demand(COD)removal rate and the 2-HA degradation rate were used as indicators to evaluate the catalytic performance.The results of the experiment indicated that the solid-melting method was more conducive to preparing the catalyst when the Co/Fe molar ratio of 7:3 and the optimal structural properties of the catalysts were achieved.The influence of operating parameters,including reaction temperature,catalyst dosage,H_(2)O_(2)dosage,pH,and initial 2-HA concentration,were optimized for the degradation of 2-HA by CWPO.The results showed that 97.64%of 2-HA degradation and 75.23%of COD removal rate were achieved under more suitable experimental conditions.In addition,after the catalyst was used five times,the degradation rate of 2-HA could still reach 76.93%,which implied the high stability and reusability of the catalyst.The high catalytic activity of the catalyst was due to the doping of Co into PrFeO_(3),which could promote the generation of HO·,and the high stability could be attributed to the loading of Pr(S)onto Al-Mt,which reduced the leaching of reactive metals.The study of reaction mechanism and kinetics showed that the whole degradation process conformed to the pseudo-firstorder kinetic equation,and the Langmuir-Hinshelwood method was applied to demonstrate that catalysis was dominant in the degradation process.

Ferroptosis:Iron-mediated cell death linked to disease pathogenesis

Ferroptosis is a pattern of iron-mediated regulatory cell death characterized by oxidative damage.The molecular regulatory mechanisms are related to iron metabolism,lipid peroxidation,and glutathione metabolism.Additionally,some immunological signaling pathways,such as the cyclic GMP-AMP synthase-stimulator of the interferon gene axis,the Janus kinase-signal transducer and activator of transcription 1 axis,and the transforming growth factor beta 1-Smad3 axis,may also participate in the regulation of ferroptosis.Studies have shown that ferroptosis is significantly associated with many diseases such as cancer,neurodegenerative diseases,inflammatory diseases,and autoimmune diseases.Considering the pivotal role of ferroptosis-regulating signaling in the pathogenesis of diverse diseases,the development of ferroptosis inducers or inhibitors may have significant clinical potential for the treatment of aforementioned conditions.

Fibroblast growth factor 21 inhibits ferroptosis following spinal cord injury by regulating heme oxygenase-1

Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.

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.

Correction to“Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence of primary liver cancer”

Correction to“Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence and development of primary liver cancer”in World J Gastrointest Oncol 2024;16:2335-2349,published by Shu YJ,Lao B,and Qiu YY.In this article,we added the correct citations of images.

UV-Based Advanced Oxidation Processes for Antibiotic Resistance Control: Efficiency, Influencing Factors, and Energy Consumption

Antibiotic resistant bacteria(ARB)with antibiotic resistance genes(ARGs)can reduce or eliminate the effectiveness of antibiotics and thus threaten human health.The United Nations Environment Programme considers antibiotic resistance the first of six emerging issues of concern.Advanced oxidation processes(AOPs)that combine ultraviolet(UV)irradiation and chemical oxidation(primarily chlorine,hydrogen peroxide,and persulfate)have attracted increasing interest as advanced water and wastewater treatment technologies.These integrated technologies have been reported to significantly elevate the efficiencies of ARB inactivation and ARG degradation compared with direct UV irradiation or chemical oxidation alone due to the generation of multiple reactive species.In this study,the performance and underlying mechanisms of UV/chlorine,UV/hydrogen peroxide,and UV/persulfate processes for controlling ARB and ARGs were reviewed based on recent studies.Factors affecting the process-specific efficiency in controlling ARB and ARGs were discussed,including biotic factors,oxidant dose,UV fluence,pH,and water matrix properties.In addition,the cost-effectiveness of the UV-based AOPs was evaluated using the concept of electrical energy per order.The UV/chlorine process exhibited a higher efficiency with lower energy consumption than other UV-based AOPs in the wastewater matrix,indicating its potential for ARB inactivation and ARG degradation in wastewater treatment.Further studies are required to address the trade-off between toxic byproduct formation and the energy efficiency of the UV/chlorine process in real wastewater to facilitate its optimization and application in the control of ARB and ARGs.