Background:This study evaluated the use of dietary vitamin E and polyphenols on growth,immune and oxidative status of weaned pigs fed peroxidized lipids.A total of 192 piglets(21 days of age and body weight of 6.62...Background:This study evaluated the use of dietary vitamin E and polyphenols on growth,immune and oxidative status of weaned pigs fed peroxidized lipids.A total of 192 piglets(21 days of age and body weight of 6.62±1.04 kg)were assigned within sex and weight blocks to a 2×3 factorial arrangement using 48 pens with 4 pigs per pen.Dietary treatments consisted of lipid peroxidation(6%edible soybean oil or 6%peroxidized soybean oil),and antioxidant supplementation(control diet containing 33 IU/kg DL-α-tocopheryl-acetate;control with 200 IU/kg additional dl-α-tocopheryl-acetate;or control with 400 mg/kg polyphenols).Pigs were fed in 2 phases for 14 and 21 days,respectively.Results:Peroxidation of oil for 12 days at 80°C with exposure to 50 L/min of air substantially increased peroxide values,anisidine value,hexanal,and 2,4-decadienal concentrations.Feeding peroxidized lipids decreased(P<0.001)body weight(23.16 vs.18.74 kg),daily gain(473 vs.346 g/d),daily feed intake(658 vs.535 g/d)and gain:feed ratio(719 vs.647 g/kg).Lipid peroxidation decreased serum vitamin E(P<0.001)and this decrease was larger on day 35(1.82 vs.0.81 mg/kg)than day 14(1.95 vs.1.38 mg/kg).Supplemental vitamin E,but not polyphenols,increased(P≤0.002)serum vitamin E by 84%and 22%for control and peroxidized diets,respectively(interaction,P=0.001).Serum malondialdehyde decreased(P<0.001)with peroxidation on day 14,but not day 35 and protein carbonyl increased(P<0.001)with peroxidation on day 35,but not day 14.Serum 8-hydroxydeoxyguanosine was not affected(P>0.05).Total antioxidant capacity decreased with peroxidation(P<0.001)and increased with vitamin E(P=0.065)and polyphenols(P=0.046)for the control oil diet only.Serum cytokine concentrations increased with feeding peroxidized lipids on day 35,but were not affected by antioxidant supplementation(P>0.05).Conclusion:Feeding peroxidized lipids negatively impacted growth performance and antioxidant capacity of nursery pigs.Supplementation of vitamin E and polyphenols improved total antioxidant capacity,especially in pigs fed control diets,but did not restore growth performance.展开更多
Mouse peritoneal macrophages were incubated in DMEM with pox-LDL and Rradlx Salviae Miltiorrhizae (RSM) to investigate the effects of RSM on the internalization of peroxidized low density lipoprotein (pox-LDL) by usin...Mouse peritoneal macrophages were incubated in DMEM with pox-LDL and Rradlx Salviae Miltiorrhizae (RSM) to investigate the effects of RSM on the internalization of peroxidized low density lipoprotein (pox-LDL) by using lipid analysis and electron microscopy. Lipid peroxide (LPO) concentrations were increased slightly in the medium after incubation of macrophages with normal LDL (n-LDL), while decreased significantly in the media after incubation of macrophages with pox-LDL. In the three groups with pox-LDL, it could be found that there was a dose-dependent decrease of concentrations of LPO and total cholesterol (TCH) in the two RSM groups, and the decrease in the two RSM groups was much greater than in the group without RSM. RSM accelerated a more decrease of LPO than cholesterol contents in the media containing pox-LDL. The ultrastructural studies also showed that RSM induced the accumulation of lipid droplets in the cytoplasm of mouse peritoneal macrophages. The results suggested that RSM could accelerate the phagocytosis and degradation of pox-LDL by macrophages.展开更多
This study investigated the effect of peroxidized lipids on piglets’ growth performance, intestinal morphology, inflammatory reactions, oxidative stress in the liver, duodenum, jejunum, ileum, and colon,and ileal mic...This study investigated the effect of peroxidized lipids on piglets’ growth performance, intestinal morphology, inflammatory reactions, oxidative stress in the liver, duodenum, jejunum, ileum, and colon,and ileal microbiota. Twenty piglets (Duroc×[Landrace×Yorkshire];age=21 d old, BW=6.5±1 kg)were randomly assigned to two groups with 10 replicates per group and one piglet per replicate. The control group was fed 6%fresh soybean oil and the peroxidized soybean oil (PSO) group fed 6%PSO. The experimental feeding period lasted 24 d. The study found no impact on ADFI, ADG and gain to feed ratio(P> 0.05). However, the PSO group increased the diarrhea index and the serum levels of lactate dehydrogenase triglycerides, cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (P <0.05), along with decreased concentrations of alanine aminotransferase and blood urea nitrogen (P <0.05). For oxidative enzymes, PSO increased the concentration of F2-isoprostane in urine(P=0.032), malondialdehyde (MDA) in the duodenum (P=0.001) and jejunum (P=0.004), decreased thiobarbituric acid reactive substances (TBARS) in the liver (P=0.001) but increased TBARS in duodenum(P=0.001), and carbonylated proteins in the duodenum (P=0.003). For antioxidant enzymes, PSO decreased superoxide dismutase (SOD) in the liver (P=0.001), colon (P=0.002), and jejunum(P=0.015), along with glutathione peroxidase (GSH-Px) in the liver (P=0.008) and NAD(P)H:quinone oxidoreductase 1 (NQO1) in ileum (P=0.001). For inflammatory reactions, PSO increased interleukin(IL)-1β concentrations in the duodenum and colon, and IL-10 in the jejunum, while decreasing IL-4concentration in the duodenum (P <0.05). For intestinal morphology and ileal microbiota, PSO increased ileal crypt depth, while decreasing the crypt-to-villus ratio (P <0.05). Peroxidized soybean oil increased the relative abundance of Prevotella, Clostridium_sensu_stricto_1, Clostridium_sensu_stricto_6,Pasteurella and Klebsiella (P <0.05). In conclusion, this study revealed that PSO worsened diarrhea,increasing the ileal crypt depth and the relative abundance of harmful microbiota, and induced oxidative stress and inflammation in the intestines and liver, primarily in the jejunum and ileum.展开更多
Dynamic melt modification of polyethylene via the direct grafting of peroxide fragments shows promise for the development of processable functionalized materials.In this study,four linear low-density polyethylenes(LLD...Dynamic melt modification of polyethylene via the direct grafting of peroxide fragments shows promise for the development of processable functionalized materials.In this study,four linear low-density polyethylenes(LLDPEs)with comparable molecular weights but different short-chain branch(SCB)contents(ranging of 5-66 per 1000 carbon atoms)were modified via dynamic melt mixing using 2 wt% benzoyl peroxide at 145℃ and 50 r/min for 30 min.The influence of SCB content on the processability and structure of the resulting products was systematically investigated.All modified products exhibited good melt processability with melt flow rates(MFR)ranging from 0.46 g/10min to 1.07 g/10min.Products derived from low-SCB LLDPEs showed a lower MFR,higher cross-linking content,a larger number of long-chain branches,and a higher degree of benzoyl grafting.In contrast,those produced from high-SCB LLDPEs exhibited improved processability,reduced cross-linking,fewer long-chain branches,and lower benzoyl grafting levels.A detailed structural investigation of the soluble and insoluble fractions,which were separated using trichlorobenzene fractionation,was conducted to analyze the structural features of various modified products and demonstrate that the SCB content(i.e.,tertiary carbon density)significantly influences radical coupling during dynamic modification.Elevated tertiary carbon density,by introducing greater steric hindrance,suppresses radical coupling during dynamic modification,thereby reducing the efficiency of both crosslinking and peroxide fragment grafting.These findings provide new insights into the structure-reactivity relationships in peroxide-induced polyethylene modification and lay the foundation for tailoring material properties via dynamic processing.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithel...BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.展开更多
The efficient and sustainable removal of refractory high ionization potential(high-IP)organic pollutants remains challenging due to their redox inertness and poor interfacial electron transfer.Herein,we report a suspe...The efficient and sustainable removal of refractory high ionization potential(high-IP)organic pollutants remains challenging due to their redox inertness and poor interfacial electron transfer.Herein,we report a suspended photo-Fenton membrane (2D-C_(3)N_(4)/Fe-N-C/GO) that circumvents these limitations via a self-sufficient oxidant generation pathway,enabling low-carbon abatement of high-IP pollutants.This multifunctional architecture couples the visible-light-driven production of hydrogen peroxide(H_(2)O_(2)) by two-dimensional carbon nitride(2D-C_(3)N_(4)) with the Fe-N-C mediated adsorption and activation of electron-deficient species via pyridinic N-Fe^(2+)/Fe^(3+) redox pairs.Under light irradiation,photogenerated electrons continuously regenerate Fe^(2+) from Fe^(3+),sustaining reactive oxygen species(·OH)production and promoting efficient oxidative mineralization.The system demonstrates robust long-term performance in both synthetic and real wastewater matrices,achieving superior degradation and chemical oxygen demand(COD)removal.Life cycle assessment(LCA)confirms its environmental superiority over conventional homogeneous Fenton processes,with markedly reduced carbon emissions and ecological impacts.This work offers a mechanistically insightful and practically viable platform for the green,efficient,and durable remediation of high-IP organic pollutants,providing conceptual guidance for next-generation catalytic wastewater treatment technologies.展开更多
Lipid peroxidation of polyunsaturate fatty acid is the main reason for the production of toxic materials in putrid food oil. The free radicals and other products produced from the peroxidation process can damage the m...Lipid peroxidation of polyunsaturate fatty acid is the main reason for the production of toxic materials in putrid food oil. The free radicals and other products produced from the peroxidation process can damage the membrane, protein and DNA and may induce cancer and other brain, myocardial and vascular diseases. Lipid peroxidation is also an important reason for aging. So it has raised a wide interest and attention of biological and展开更多
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. Oxid...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.展开更多
Ferroptosis,a type of programmed cell death,represents a distinct paradigm in cell biology.It is characterized by the iron-dependent accumulation of reactive oxygen species,which induce lipid peroxidation(LPO),and is ...Ferroptosis,a type of programmed cell death,represents a distinct paradigm in cell biology.It is characterized by the iron-dependent accumulation of reactive oxygen species,which induce lipid peroxidation(LPO),and is orchestrated by the interplay between iron,lipid peroxides,and glutathione.In this review,we emphasize the frequently overlooked role of iron in LPO beyond the classical iron-driven Fenton reaction in several crucial processes that regulate cellular iron homeostasis,including iron intake and export as well as ferritinophagy,and the emerging roles of endoplasmic reticulum-resident flavoprotein oxidoreductases,especially P450 oxidoreductases,in modulating LPO.We summarize how various types of fatty acids(FAs),including saturated,monounsaturated,and polyunsaturated FAs,differentially influence ferroptosis when incorporated into phospholipids.Furthermore,we highlight the therapeutic potential of targeting LPO to mitigate ferroptosis and discuss the regulatory mechanisms of endogenous lipophilic radical-trapping antioxidants that confer resistance to ferroptosis,shedding light on therapeutic avenues for ferroptosis-associated diseases.展开更多
Ulcerative colitis has baffled researchers since the early 20th century.The pre-vailing explanation attributes the chronic recurring episodes of bloody diarrhea and abdominal pain to some form of immune abnormality,de...Ulcerative colitis has baffled researchers since the early 20th century.The pre-vailing explanation attributes the chronic recurring episodes of bloody diarrhea and abdominal pain to some form of immune abnormality,despite the lack of supporting evidence.This highlights the critical need for innovative research directions and methodologies to uncover the cause and develop a cure for this disease.By analyzing existing data from less than a dozen previously published studies,a novel,evidence-based pathogenesis was constructed,implicating colonic epithelial hydrogen peroxide as a causal factor in the development of this disease.This newly identified mechanism informed the creation of a ground-breaking class of therapeutics,known as reducing agents,which have demon-strated remarkable success in resolving colonic inflammation and restoring colonic health in patients with refractory ulcerative colitis.This paper outlines the timeline of these publications and reinterprets the findings within the context of contemporary biomedical science.展开更多
Gastric Carcinoma(GC)is a highly fatal malignant tumor with a poor prognosis.Its elevated mortality rates are primarily due to its proclivity for late-stage metastasis.Exploring the metabolic interactions between tumo...Gastric Carcinoma(GC)is a highly fatal malignant tumor with a poor prognosis.Its elevated mortality rates are primarily due to its proclivity for late-stage metastasis.Exploring the metabolic interactions between tumor microenvironment and the systemic bloodstream could help to clearly understand the mechanisms and identify precise biomarkers of tumor growth,proliferation,and metastasis.In this study,an integrative approach that combines plasma metabolomics with mass spectrometry imaging of tumor tissue was developed to investigate the global metabolic landscape of GC tumorigenesis and metastasis.The results showed that the oxidized glutathione to glutathione ratio(GSSH/GSH)became increased in non-distal metastatic GC(M0),which means an accumulation of oxidative stress in tumor tissues.Furthermore,it was found that the peroxidation of polyunsaturated fatty acids,such as 9,10-EpOMe,9-HOTrE,etc.,were accelerated in both plasma and tumor tissues of distal metastatic GC(M1).These changes were further confirmed the potential effect of CYP2E1 and GGT1 in metastatic potential of GC by mass spectrometry imaging(MSI)and immunohistochemistry(IHC).Collectively,our findings reveal the integrated multidimensional metabolomics approach is a clinical useful method to unravel the bloodtumor metabolic crosstalk,illuminate reprogrammed metabolic networks,and provide reliable circulating biomarkers.展开更多
BACKGROUND Fistula-in-ano is an abnormal tunnel formation linking the anal canal with the perineum and perianal skin.Multiple imagining methods are available to evaluate it,among which magnetic resonance imaging(MRI)i...BACKGROUND Fistula-in-ano is an abnormal tunnel formation linking the anal canal with the perineum and perianal skin.Multiple imagining methods are available to evaluate it,among which magnetic resonance imaging(MRI)is the most advanced nonin-vasive preoperative method.However,it is limited in its visualization function.AIM To investigate the use of intraluminal MRI for perianal fistulas via a novel direct MRI fistulography method.METHODS We mixed 3%hydrogen peroxide(HP)with gadolinium for HPMRI fistulogra-phy,retrospectively analyzing 60 cases of complex/recurrent fistula-in-ano using physical examination,trans-perineal ultrasonography(TPUS),low-spatial-reso-lution MRI,and high-resolution direct HPMRI fistulography.We assessed detec-tion rates of fistula tracks,internal openings,their relationship with anal sphinc-ters,and perianal abscesses using statistical analyses,including interobserver agreement(Kappa statistic),and compared results with intraoperative findings.RESULTS Surgical confirmation in 60 cases showed that high-resolution direct HPMRI fis-tulography provided superior detection rates for internal openings(153)and fistula tracks(162)compared to physical exams,TPUS,and low-spatial-resolution MRI(Z>5.7,P<0.05).The effectiveness of physical examination and TPUS was also inferior to that of our method for detecting perianal abscesses(54)(Z=6.773,3.694,P<0.05),whereas that of low-spatial-resolution MRI was not significantly different(Z=1.851,P=0.06).High-resolution direct HPMRI fistulography also achieved the highest interobserver agreement(Kappa:0.89,0.85,and 0.80),while low-spatial-resolution MRI showed moderate agreement(Kappa:0.78,0.74,and 0.69).TPUS and physical examination had lower agreement(Kappa range:0.33-0.63).CONCLUSION High-resolution direct HPMRI fistulography enhances the visualization of recurrent and complex fistula-in-ano,including branched fistulas,allowing for precise planning and improved surgical outcomes.展开更多
Selective electrocatalysis of two-electron oxygen reduction reaction(2e^(-)ORR)has been recognized as a sustainable and on-site process for hydrogen peroxide(H_(2)O_(2))production.Great progress has been achieved for ...Selective electrocatalysis of two-electron oxygen reduction reaction(2e^(-)ORR)has been recognized as a sustainable and on-site process for hydrogen peroxide(H_(2)O_(2))production.Great progress has been achieved for 2e^(-)ORR in alkaline media.However,it is challenged by insufficient activity and selectiv-ity of the catalysts in acidic electrolytes.Herein,we report sulfur-poisoned PtNi/C catalysts(PtNiSx/C)that could regulate ORR from the 4e^(-)to 2e^(-)pathway.The identified PtNiS0.6/C offers high activity in terms of onset potential of∼0.69 V(vs.RHE)and∼80%selectivity.The mass activity is also compara-ble and outperforms representative Pt-based precious and transition-metal-based catalysts.In addition,it is interestingly found that the Faradaic efficiency further increased to 95%during the long-term elec-trolysis test due to Ni atom surface migration.The electrochemical production of the H_(2)O_(2)system was applied to the electro-Fenton process,which has realized the effective degradation of organic pollutants.This work offers a strategy by sulfur poisoning PtNi/C catalyst to realize Pt-based 2e^(-)ORR active catalysts to electrolysis of H_(2)O_(2)in acidic media.展开更多
Hydrogen peroxide(H_(2)O_(2))is a crucial,eco-friendly oxidizing agent with a wide range of industrial,environmental,and biomedical applications.Traditional production methods,such as the anthraquinone process,face si...Hydrogen peroxide(H_(2)O_(2))is a crucial,eco-friendly oxidizing agent with a wide range of industrial,environmental,and biomedical applications.Traditional production methods,such as the anthraquinone process,face significant challenges in terms of energy consumption and environmental impact.As a sustainable alternative,photocatalytic H_(2)O_(2) production,driven by solar energy,has emerged as a promising approach.This review discusses the key advancements in photocatalytic H_(2)O_(2) synthesis,focusing on overcoming challenges such as charge recombination,selectivity for the two-electron oxygen reduction reaction(2e^(-)ORR),and catalyst stability.Recent innovations in photocatalyst design,including high-entropy materials,single-atom catalysts,and covalent organic frameworks(COFs),have significantly enhanced efficiency and stability.Furthermore,novel strategies for optimizing charge separation,light harvesting,and mass transfer are explored.The integration of artificial intelligence and bioinspired systems holds potential for accelerating progress in this field.This review provides a comprehensive overview of current challenges and cutting-edge solutions,offering valuable insights for the development of scalable,decentralized H_(2)O_(2) production systems that contribute to a more sustainable future.展开更多
Electrocatalytic hydrogen peroxide(H_(2)O_(2))production via the two-electron oxygen reduction reaction(2e−ORR)is promising,but non-metal catalysts with high selectivity are lacking.Herein,a high content of pyrrolic N...Electrocatalytic hydrogen peroxide(H_(2)O_(2))production via the two-electron oxygen reduction reaction(2e−ORR)is promising,but non-metal catalysts with high selectivity are lacking.Herein,a high content of pyrrolic N doped carbon(HPNC)with small mesopores is constructed.Over 80%H_(2)O_(2) selectivity at a wide potential of 0.2–0.6 V is achieved.The finite element simulation reveals that small pore-size mesopores are beneficial to O_(2) adsorption.And in-situ characterization proves that HPNC suppresses the breakage of Osingle bondO bond and enhances the stabilization of *OOH intermediates,thus improving the 2e−ORR performance.This work highlights the combination of non-metal active sites and geometry for 2e−ORR electrocatalysis.展开更多
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 under...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).展开更多
Ferroptosis can serve as a potent strategy for regulating cell death via lipid peroxidation and the imbalance of the antioxidant system resulting from iron accumulation in triple-negative breast cancer(TNBC)therapy.Ho...Ferroptosis can serve as a potent strategy for regulating cell death via lipid peroxidation and the imbalance of the antioxidant system resulting from iron accumulation in triple-negative breast cancer(TNBC)therapy.However,the ferroptosis accompanied with down-regulation of glutathione peroxidase 4(GPX4)lead to CD36-mediated tumor-infiltrating CD8^(+)T cells uptaking fatty acids,resulting in the negative action on immunotherapeutic efficacy.Herein,the albumin nanoparticles,abbreviated as LHS NPs,were designed by co-assembly of hemin,linoleic acid-cystamine,and a CD36 inhibitor sulfosuccinimide oleate,to bi-directionally manipulated ferroptosis in tumor and CD8^(+)T cells for TNBC therapy.LHS NPs exerted more efficient reactive oxygen species generation,glutathione depletion and malondialdehyde production by the combinatory strategy of classical and non-classical ferroptosis modes,which amplified the positive action on ferroptosis in tumor cells.Meanwhile,LHS manipulated the negative action of ferroptosis by inhibiting the CD36 mediated-lipid peroxidation in CD8^(+)T cells,thereby activating the immunotherapeutic efficacy with the improvements on induction of immunogenic cell death,proliferation of CD4+CD8^(+)T cells and natural killer cells,alleviation immunosuppressive regulatory T cells and myeloid-derived suppressor cells,and repolarization of the M2-to M1-phenotype tumor-associated macrophages.Thus,LHS NPs demonstrated an improved antitumor efficacy in suppressing the tumor growth and lungmetastasis of 4T1-tumormice.Our work gives novel insights for the bi-directionally manipulating ferroptosis in tumor and CD8^(+)T cells on TNBC chemoimmunotherapy.展开更多
Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an imp...Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an important member of the glutathione S-transferase(GSTs)family,which plays an important role in maintaining cell homeostasis and detoxification.This study investigated the role and mechanism of GSTM1 in post-MI fibrosis.Methods:Multi-omics approaches(proteomics/scRNA-seq)identified GSTM1 as a dysregulated target in post-MI fibroblasts.Using a murine coronary ligation model,we assessed GSTM1 dynamics via molecular profiling,such as Western blotting,immunofluorescence,and real-time quantitative polymerase chain reaction.Adeno-associated virus serotype 9(AAV9)-mediated cardiac-specific GSTM1 overexpression was achieved through systemic delivery.In vitro studies employed transforming growth factor-β(TGF-β)-stimulated primary fibroblasts with siRNA/plasmid interventions.Mechanistic insights were derived from transcriptomics and lipid peroxidation assays.Results:The expression of GSTM1 in mouse CFs after MI was significantly down-regulated at both transcriptional and protein levels.In human dilated cardiomyopathy(DCM)patients with severe heart failure,GSTM1 expression was decreased alongside aggravated fibrosis.Overexpression of GSTM1 in post-MI mice improved cardiac function,while significantly reducing infarct size and fibrosis compared with the control group.In vitro models demonstrated that GSTM1 markedly attenuated collagen secretion and activation of fibroblasts,as well as suppressed their proliferation and migration.Further studies revealed that GSTM1 overexpression significantly inhibited the generation of intracellular and mitochondrial reactive oxygen species(ROS)under pathological conditions,suggesting that GSTM1 exerts an antioxidative stress effect in post-infarction fibroblasts.Further investigation of molecular mechanisms indicated that GSTM1 may suppress the initiation and progression of fibrosis by modulating lipid metabolism and ferroptosis-related pathways.Overexpression of GSTM1 significantly reduced lipid peroxidation and free ferrous iron levels in fibroblasts and mitochondria,markedly decreased ferroptosis-related indicators,and alleviated oxidative lipid levels[such as 12-hydroxyeicosapentaenoic acid(HEPE)and 9-,10-dihydroxy octadecenoic acid(DHOME)]under fibrotic conditions.GSTM1 enhanced the phosphorylation of signal transducer and activator of transcription 3(STAT3),thereby upregulating the downstream expression of glutathione peroxidase 4(GPX4),reducing ROS production,and mitigating fibroblast activation and phenotypic transformation by inhibiting lipid peroxidation.Conclusions:This study identifies GSTM1 as a key inhibitor of fibroblast activation and cardiac fibrosis,highlighting its ability to target ferroptosis through redox regulation.AAV-mediated GSTM1 therapy demonstrates significant therapeutic potential for improving outcomes post-MI.展开更多
Hydrogen peroxide(H_(2)O_(2)),as a green oxidant,plays a vital role in various applications,including environmental remediation,disinfection,and chemical synthesis[1].The conventional anthraquinone process,despite its...Hydrogen peroxide(H_(2)O_(2)),as a green oxidant,plays a vital role in various applications,including environmental remediation,disinfection,and chemical synthesis[1].The conventional anthraquinone process,despite its industrial maturity and high yield,suffers from high energy consumption,carbon emissions,safety risks,and reliance on precious metals[2].Despite ongoing optimizations,a more sustainable alternative is urgently needed.The direct synthesis of hydrogen peroxide from water and oxygen has long been considered as an ideal alternative due to its theoretical 100%atom efficiency and environmental sustainability.展开更多
Ferroptosis, an iron-dependent type of cell death, is being considered for new clinical treatments of malignant tumors that are difficult to treat with apoptosis inducers. Although several reports have attempted to in...Ferroptosis, an iron-dependent type of cell death, is being considered for new clinical treatments of malignant tumors that are difficult to treat with apoptosis inducers. Although several reports have attempted to increase the sensitivity of cells to cell death by combining ferroptosis and apoptosis inducers using a single treatment, detailed elucidation of the respective mechanisms of ferroptosis and apoptosis during cell death remains unclear. Here, we evaluated combined treatment effectiveness using the apoptosis-sensitive rat insulinoma INS-1 cell lines. DNA laddering, an indicator of camptothecin (CPT)-induced apoptosis, was abolished by adding RSL3 and ML-162, but not erastin. We found that when the cells were treated with the apoptosis inducer CPT or the ferroptosis inducer RSL3, respectively, the degree of cytotoxicity observed increased dose-dependently. However, a combined CPT and RSL3 treatment did not show a synergistic decrease in cell viability. Camptothecin did not significantly affect increases in intracellular lipid peroxidation and reactive oxygen species or increases in mitochondrial and cytoplasmic free iron levels that were induced by treatment with RSL3 alone. Moreover, deferoxamine and α-tocopherol were found to inhibit RSL3-induced cytotoxicity but did not protect against CPT or CPT and RSL3-induced cytotoxicity. Finally, the exogenous addition of tert-butyl hydroperoxide inhibited DNA ladder formation that is induced by CPT, while the addition of hydrogen peroxide or ferrous ammonium sulfate had no effect. Taken together, these results suggest that lipid peroxides generated during ferroptosis may suppress cell death induced by apoptotic mechanisms.展开更多
基金the Peruvian National Fund,for Scientific,Technological,and Technological Innovation Development(FONDECYT)the funding branch of the National Council for Science,Technological,and Technological Innovation Development(CONCYTEC)Peru(grant contract N°233-2015-FONDECYT)for providing a doctoral scholarship to Ysenia Victoria Silva-Guillen.
文摘Background:This study evaluated the use of dietary vitamin E and polyphenols on growth,immune and oxidative status of weaned pigs fed peroxidized lipids.A total of 192 piglets(21 days of age and body weight of 6.62±1.04 kg)were assigned within sex and weight blocks to a 2×3 factorial arrangement using 48 pens with 4 pigs per pen.Dietary treatments consisted of lipid peroxidation(6%edible soybean oil or 6%peroxidized soybean oil),and antioxidant supplementation(control diet containing 33 IU/kg DL-α-tocopheryl-acetate;control with 200 IU/kg additional dl-α-tocopheryl-acetate;or control with 400 mg/kg polyphenols).Pigs were fed in 2 phases for 14 and 21 days,respectively.Results:Peroxidation of oil for 12 days at 80°C with exposure to 50 L/min of air substantially increased peroxide values,anisidine value,hexanal,and 2,4-decadienal concentrations.Feeding peroxidized lipids decreased(P<0.001)body weight(23.16 vs.18.74 kg),daily gain(473 vs.346 g/d),daily feed intake(658 vs.535 g/d)and gain:feed ratio(719 vs.647 g/kg).Lipid peroxidation decreased serum vitamin E(P<0.001)and this decrease was larger on day 35(1.82 vs.0.81 mg/kg)than day 14(1.95 vs.1.38 mg/kg).Supplemental vitamin E,but not polyphenols,increased(P≤0.002)serum vitamin E by 84%and 22%for control and peroxidized diets,respectively(interaction,P=0.001).Serum malondialdehyde decreased(P<0.001)with peroxidation on day 14,but not day 35 and protein carbonyl increased(P<0.001)with peroxidation on day 35,but not day 14.Serum 8-hydroxydeoxyguanosine was not affected(P>0.05).Total antioxidant capacity decreased with peroxidation(P<0.001)and increased with vitamin E(P=0.065)and polyphenols(P=0.046)for the control oil diet only.Serum cytokine concentrations increased with feeding peroxidized lipids on day 35,but were not affected by antioxidant supplementation(P>0.05).Conclusion:Feeding peroxidized lipids negatively impacted growth performance and antioxidant capacity of nursery pigs.Supplementation of vitamin E and polyphenols improved total antioxidant capacity,especially in pigs fed control diets,but did not restore growth performance.
文摘Mouse peritoneal macrophages were incubated in DMEM with pox-LDL and Rradlx Salviae Miltiorrhizae (RSM) to investigate the effects of RSM on the internalization of peroxidized low density lipoprotein (pox-LDL) by using lipid analysis and electron microscopy. Lipid peroxide (LPO) concentrations were increased slightly in the medium after incubation of macrophages with normal LDL (n-LDL), while decreased significantly in the media after incubation of macrophages with pox-LDL. In the three groups with pox-LDL, it could be found that there was a dose-dependent decrease of concentrations of LPO and total cholesterol (TCH) in the two RSM groups, and the decrease in the two RSM groups was much greater than in the group without RSM. RSM accelerated a more decrease of LPO than cholesterol contents in the media containing pox-LDL. The ultrastructural studies also showed that RSM induced the accumulation of lipid droplets in the cytoplasm of mouse peritoneal macrophages. The results suggested that RSM could accelerate the phagocytosis and degradation of pox-LDL by macrophages.
基金funded by National Natural Science Foundation of China(32130099).
文摘This study investigated the effect of peroxidized lipids on piglets’ growth performance, intestinal morphology, inflammatory reactions, oxidative stress in the liver, duodenum, jejunum, ileum, and colon,and ileal microbiota. Twenty piglets (Duroc×[Landrace×Yorkshire];age=21 d old, BW=6.5±1 kg)were randomly assigned to two groups with 10 replicates per group and one piglet per replicate. The control group was fed 6%fresh soybean oil and the peroxidized soybean oil (PSO) group fed 6%PSO. The experimental feeding period lasted 24 d. The study found no impact on ADFI, ADG and gain to feed ratio(P> 0.05). However, the PSO group increased the diarrhea index and the serum levels of lactate dehydrogenase triglycerides, cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (P <0.05), along with decreased concentrations of alanine aminotransferase and blood urea nitrogen (P <0.05). For oxidative enzymes, PSO increased the concentration of F2-isoprostane in urine(P=0.032), malondialdehyde (MDA) in the duodenum (P=0.001) and jejunum (P=0.004), decreased thiobarbituric acid reactive substances (TBARS) in the liver (P=0.001) but increased TBARS in duodenum(P=0.001), and carbonylated proteins in the duodenum (P=0.003). For antioxidant enzymes, PSO decreased superoxide dismutase (SOD) in the liver (P=0.001), colon (P=0.002), and jejunum(P=0.015), along with glutathione peroxidase (GSH-Px) in the liver (P=0.008) and NAD(P)H:quinone oxidoreductase 1 (NQO1) in ileum (P=0.001). For inflammatory reactions, PSO increased interleukin(IL)-1β concentrations in the duodenum and colon, and IL-10 in the jejunum, while decreasing IL-4concentration in the duodenum (P <0.05). For intestinal morphology and ileal microbiota, PSO increased ileal crypt depth, while decreasing the crypt-to-villus ratio (P <0.05). Peroxidized soybean oil increased the relative abundance of Prevotella, Clostridium_sensu_stricto_1, Clostridium_sensu_stricto_6,Pasteurella and Klebsiella (P <0.05). In conclusion, this study revealed that PSO worsened diarrhea,increasing the ileal crypt depth and the relative abundance of harmful microbiota, and induced oxidative stress and inflammation in the intestines and liver, primarily in the jejunum and ileum.
基金financially supported by the Science and Technology Project of PetroChina Company Limited,China(No.2022DJ6314)the National Natural Science Foundation of China(No.52173056)。
文摘Dynamic melt modification of polyethylene via the direct grafting of peroxide fragments shows promise for the development of processable functionalized materials.In this study,four linear low-density polyethylenes(LLDPEs)with comparable molecular weights but different short-chain branch(SCB)contents(ranging of 5-66 per 1000 carbon atoms)were modified via dynamic melt mixing using 2 wt% benzoyl peroxide at 145℃ and 50 r/min for 30 min.The influence of SCB content on the processability and structure of the resulting products was systematically investigated.All modified products exhibited good melt processability with melt flow rates(MFR)ranging from 0.46 g/10min to 1.07 g/10min.Products derived from low-SCB LLDPEs showed a lower MFR,higher cross-linking content,a larger number of long-chain branches,and a higher degree of benzoyl grafting.In contrast,those produced from high-SCB LLDPEs exhibited improved processability,reduced cross-linking,fewer long-chain branches,and lower benzoyl grafting levels.A detailed structural investigation of the soluble and insoluble fractions,which were separated using trichlorobenzene fractionation,was conducted to analyze the structural features of various modified products and demonstrate that the SCB content(i.e.,tertiary carbon density)significantly influences radical coupling during dynamic modification.Elevated tertiary carbon density,by introducing greater steric hindrance,suppresses radical coupling during dynamic modification,thereby reducing the efficiency of both crosslinking and peroxide fragment grafting.These findings provide new insights into the structure-reactivity relationships in peroxide-induced polyethylene modification and lay the foundation for tailoring material properties via dynamic processing.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.
基金supported by the National Natural Science Foundation of China(22325602,22521201,22176060,and 22406142)the"National Key R&D Program of China"(SQ2024YFA1211001)+3 种基金the Program of Shanghai Academic/Technology Research Leader(23XD1421000)Key Laboratory of Functional Inorganic Material Chemistry(Heilongjiang University)Ministry of Education(KIM-0-2025017)State Key Laboratory of Water Pollution Control and Green Resource Recycling Foundation(PCRRF250014).
文摘The efficient and sustainable removal of refractory high ionization potential(high-IP)organic pollutants remains challenging due to their redox inertness and poor interfacial electron transfer.Herein,we report a suspended photo-Fenton membrane (2D-C_(3)N_(4)/Fe-N-C/GO) that circumvents these limitations via a self-sufficient oxidant generation pathway,enabling low-carbon abatement of high-IP pollutants.This multifunctional architecture couples the visible-light-driven production of hydrogen peroxide(H_(2)O_(2)) by two-dimensional carbon nitride(2D-C_(3)N_(4)) with the Fe-N-C mediated adsorption and activation of electron-deficient species via pyridinic N-Fe^(2+)/Fe^(3+) redox pairs.Under light irradiation,photogenerated electrons continuously regenerate Fe^(2+) from Fe^(3+),sustaining reactive oxygen species(·OH)production and promoting efficient oxidative mineralization.The system demonstrates robust long-term performance in both synthetic and real wastewater matrices,achieving superior degradation and chemical oxygen demand(COD)removal.Life cycle assessment(LCA)confirms its environmental superiority over conventional homogeneous Fenton processes,with markedly reduced carbon emissions and ecological impacts.This work offers a mechanistically insightful and practically viable platform for the green,efficient,and durable remediation of high-IP organic pollutants,providing conceptual guidance for next-generation catalytic wastewater treatment technologies.
基金Project supported by the National Natural Science Foundation of China
文摘Lipid peroxidation of polyunsaturate fatty acid is the main reason for the production of toxic materials in putrid food oil. The free radicals and other products produced from the peroxidation process can damage the membrane, protein and DNA and may induce cancer and other brain, myocardial and vascular diseases. Lipid peroxidation is also an important reason for aging. So it has raised a wide interest and attention of biological and
基金supported by the National Natural Science Foundation of China,No.82071442 (to LS)a grant from the Jilin Provincial Department of Finance,No.JLSWSRCZX2021-004 (to LS)。
文摘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.
基金supported by grants from the National Natural Science Foundation of China(22076104)the“Taishan Scholars”Program for Young Expert of Shandong Province(tsqn202103105).
文摘Ferroptosis,a type of programmed cell death,represents a distinct paradigm in cell biology.It is characterized by the iron-dependent accumulation of reactive oxygen species,which induce lipid peroxidation(LPO),and is orchestrated by the interplay between iron,lipid peroxides,and glutathione.In this review,we emphasize the frequently overlooked role of iron in LPO beyond the classical iron-driven Fenton reaction in several crucial processes that regulate cellular iron homeostasis,including iron intake and export as well as ferritinophagy,and the emerging roles of endoplasmic reticulum-resident flavoprotein oxidoreductases,especially P450 oxidoreductases,in modulating LPO.We summarize how various types of fatty acids(FAs),including saturated,monounsaturated,and polyunsaturated FAs,differentially influence ferroptosis when incorporated into phospholipids.Furthermore,we highlight the therapeutic potential of targeting LPO to mitigate ferroptosis and discuss the regulatory mechanisms of endogenous lipophilic radical-trapping antioxidants that confer resistance to ferroptosis,shedding light on therapeutic avenues for ferroptosis-associated diseases.
文摘Ulcerative colitis has baffled researchers since the early 20th century.The pre-vailing explanation attributes the chronic recurring episodes of bloody diarrhea and abdominal pain to some form of immune abnormality,despite the lack of supporting evidence.This highlights the critical need for innovative research directions and methodologies to uncover the cause and develop a cure for this disease.By analyzing existing data from less than a dozen previously published studies,a novel,evidence-based pathogenesis was constructed,implicating colonic epithelial hydrogen peroxide as a causal factor in the development of this disease.This newly identified mechanism informed the creation of a ground-breaking class of therapeutics,known as reducing agents,which have demon-strated remarkable success in resolving colonic inflammation and restoring colonic health in patients with refractory ulcerative colitis.This paper outlines the timeline of these publications and reinterprets the findings within the context of contemporary biomedical science.
基金financial support from the National Key R&D Program of China(No.2022YFC3401003)the National Natural Science Foundation of China(Nos.21927808,82073817,22104160)。
文摘Gastric Carcinoma(GC)is a highly fatal malignant tumor with a poor prognosis.Its elevated mortality rates are primarily due to its proclivity for late-stage metastasis.Exploring the metabolic interactions between tumor microenvironment and the systemic bloodstream could help to clearly understand the mechanisms and identify precise biomarkers of tumor growth,proliferation,and metastasis.In this study,an integrative approach that combines plasma metabolomics with mass spectrometry imaging of tumor tissue was developed to investigate the global metabolic landscape of GC tumorigenesis and metastasis.The results showed that the oxidized glutathione to glutathione ratio(GSSH/GSH)became increased in non-distal metastatic GC(M0),which means an accumulation of oxidative stress in tumor tissues.Furthermore,it was found that the peroxidation of polyunsaturated fatty acids,such as 9,10-EpOMe,9-HOTrE,etc.,were accelerated in both plasma and tumor tissues of distal metastatic GC(M1).These changes were further confirmed the potential effect of CYP2E1 and GGT1 in metastatic potential of GC by mass spectrometry imaging(MSI)and immunohistochemistry(IHC).Collectively,our findings reveal the integrated multidimensional metabolomics approach is a clinical useful method to unravel the bloodtumor metabolic crosstalk,illuminate reprogrammed metabolic networks,and provide reliable circulating biomarkers.
基金Supported by Bozhou Key Research and Development Project,No.bzzc2020031.
文摘BACKGROUND Fistula-in-ano is an abnormal tunnel formation linking the anal canal with the perineum and perianal skin.Multiple imagining methods are available to evaluate it,among which magnetic resonance imaging(MRI)is the most advanced nonin-vasive preoperative method.However,it is limited in its visualization function.AIM To investigate the use of intraluminal MRI for perianal fistulas via a novel direct MRI fistulography method.METHODS We mixed 3%hydrogen peroxide(HP)with gadolinium for HPMRI fistulogra-phy,retrospectively analyzing 60 cases of complex/recurrent fistula-in-ano using physical examination,trans-perineal ultrasonography(TPUS),low-spatial-reso-lution MRI,and high-resolution direct HPMRI fistulography.We assessed detec-tion rates of fistula tracks,internal openings,their relationship with anal sphinc-ters,and perianal abscesses using statistical analyses,including interobserver agreement(Kappa statistic),and compared results with intraoperative findings.RESULTS Surgical confirmation in 60 cases showed that high-resolution direct HPMRI fis-tulography provided superior detection rates for internal openings(153)and fistula tracks(162)compared to physical exams,TPUS,and low-spatial-resolution MRI(Z>5.7,P<0.05).The effectiveness of physical examination and TPUS was also inferior to that of our method for detecting perianal abscesses(54)(Z=6.773,3.694,P<0.05),whereas that of low-spatial-resolution MRI was not significantly different(Z=1.851,P=0.06).High-resolution direct HPMRI fistulography also achieved the highest interobserver agreement(Kappa:0.89,0.85,and 0.80),while low-spatial-resolution MRI showed moderate agreement(Kappa:0.78,0.74,and 0.69).TPUS and physical examination had lower agreement(Kappa range:0.33-0.63).CONCLUSION High-resolution direct HPMRI fistulography enhances the visualization of recurrent and complex fistula-in-ano,including branched fistulas,allowing for precise planning and improved surgical outcomes.
基金financially supported by the National Natu-ral Science Foundation of China(Nos.21805052 and 22227804)the Guangdong Basic and Applied Basic Research Foundation(No.2023B1515020110)+4 种基金the Science and Technology Research Project of Guangzhou(Nos.202102020787 and 2023A03J0030)the De-partment of Science&Technology of Guangdong Province(No.2022A156)the Key Laboratory of Optoelectronic Materials and Sensors in Guangdong Provincial Universities(No.2023KSYS008)the Key Discipline of Materials Science and Engineering,Bureau of Education of Guangzhou(No.20225546)the College Student Innovation and Entrepreneurship Training Program of Guangzhou University(No.XJ202311078029).
文摘Selective electrocatalysis of two-electron oxygen reduction reaction(2e^(-)ORR)has been recognized as a sustainable and on-site process for hydrogen peroxide(H_(2)O_(2))production.Great progress has been achieved for 2e^(-)ORR in alkaline media.However,it is challenged by insufficient activity and selectiv-ity of the catalysts in acidic electrolytes.Herein,we report sulfur-poisoned PtNi/C catalysts(PtNiSx/C)that could regulate ORR from the 4e^(-)to 2e^(-)pathway.The identified PtNiS0.6/C offers high activity in terms of onset potential of∼0.69 V(vs.RHE)and∼80%selectivity.The mass activity is also compara-ble and outperforms representative Pt-based precious and transition-metal-based catalysts.In addition,it is interestingly found that the Faradaic efficiency further increased to 95%during the long-term elec-trolysis test due to Ni atom surface migration.The electrochemical production of the H_(2)O_(2)system was applied to the electro-Fenton process,which has realized the effective degradation of organic pollutants.This work offers a strategy by sulfur poisoning PtNi/C catalyst to realize Pt-based 2e^(-)ORR active catalysts to electrolysis of H_(2)O_(2)in acidic media.
基金financial support from the National Natural Science Foundation of China(No.22279143).
文摘Hydrogen peroxide(H_(2)O_(2))is a crucial,eco-friendly oxidizing agent with a wide range of industrial,environmental,and biomedical applications.Traditional production methods,such as the anthraquinone process,face significant challenges in terms of energy consumption and environmental impact.As a sustainable alternative,photocatalytic H_(2)O_(2) production,driven by solar energy,has emerged as a promising approach.This review discusses the key advancements in photocatalytic H_(2)O_(2) synthesis,focusing on overcoming challenges such as charge recombination,selectivity for the two-electron oxygen reduction reaction(2e^(-)ORR),and catalyst stability.Recent innovations in photocatalyst design,including high-entropy materials,single-atom catalysts,and covalent organic frameworks(COFs),have significantly enhanced efficiency and stability.Furthermore,novel strategies for optimizing charge separation,light harvesting,and mass transfer are explored.The integration of artificial intelligence and bioinspired systems holds potential for accelerating progress in this field.This review provides a comprehensive overview of current challenges and cutting-edge solutions,offering valuable insights for the development of scalable,decentralized H_(2)O_(2) production systems that contribute to a more sustainable future.
文摘Electrocatalytic hydrogen peroxide(H_(2)O_(2))production via the two-electron oxygen reduction reaction(2e−ORR)is promising,but non-metal catalysts with high selectivity are lacking.Herein,a high content of pyrrolic N doped carbon(HPNC)with small mesopores is constructed.Over 80%H_(2)O_(2) selectivity at a wide potential of 0.2–0.6 V is achieved.The finite element simulation reveals that small pore-size mesopores are beneficial to O_(2) adsorption.And in-situ characterization proves that HPNC suppresses the breakage of Osingle bondO bond and enhances the stabilization of *OOH intermediates,thus improving the 2e−ORR performance.This work highlights the combination of non-metal active sites and geometry for 2e−ORR electrocatalysis.
基金funding support from the Canadian Institutes of Health Researchsupported by a Doctoral Studentship from the Wings for Life Foundation。
文摘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).
基金supported by the National Nature Science Foundation of China(NO.82260699)the Science and Technology Leading Talents of Ningxia(NO.2022GKLRLX011)the West Light Foundation of The Chinese Academy of Sciences(the Science and Technology Department of Ningxia,Department of Science and Technology Cooperation[2021]NO.2).
文摘Ferroptosis can serve as a potent strategy for regulating cell death via lipid peroxidation and the imbalance of the antioxidant system resulting from iron accumulation in triple-negative breast cancer(TNBC)therapy.However,the ferroptosis accompanied with down-regulation of glutathione peroxidase 4(GPX4)lead to CD36-mediated tumor-infiltrating CD8^(+)T cells uptaking fatty acids,resulting in the negative action on immunotherapeutic efficacy.Herein,the albumin nanoparticles,abbreviated as LHS NPs,were designed by co-assembly of hemin,linoleic acid-cystamine,and a CD36 inhibitor sulfosuccinimide oleate,to bi-directionally manipulated ferroptosis in tumor and CD8^(+)T cells for TNBC therapy.LHS NPs exerted more efficient reactive oxygen species generation,glutathione depletion and malondialdehyde production by the combinatory strategy of classical and non-classical ferroptosis modes,which amplified the positive action on ferroptosis in tumor cells.Meanwhile,LHS manipulated the negative action of ferroptosis by inhibiting the CD36 mediated-lipid peroxidation in CD8^(+)T cells,thereby activating the immunotherapeutic efficacy with the improvements on induction of immunogenic cell death,proliferation of CD4+CD8^(+)T cells and natural killer cells,alleviation immunosuppressive regulatory T cells and myeloid-derived suppressor cells,and repolarization of the M2-to M1-phenotype tumor-associated macrophages.Thus,LHS NPs demonstrated an improved antitumor efficacy in suppressing the tumor growth and lungmetastasis of 4T1-tumormice.Our work gives novel insights for the bi-directionally manipulating ferroptosis in tumor and CD8^(+)T cells on TNBC chemoimmunotherapy.
基金supported by the National Natural Science Foundation of China(82270386,82070252,and 8207025)the Zhejiang Provincial Medical and Health Science and Technology Plan(2023RC020)the Zhejiang Provincial Natural Science Foundation(LR21H020001).
文摘Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an important member of the glutathione S-transferase(GSTs)family,which plays an important role in maintaining cell homeostasis and detoxification.This study investigated the role and mechanism of GSTM1 in post-MI fibrosis.Methods:Multi-omics approaches(proteomics/scRNA-seq)identified GSTM1 as a dysregulated target in post-MI fibroblasts.Using a murine coronary ligation model,we assessed GSTM1 dynamics via molecular profiling,such as Western blotting,immunofluorescence,and real-time quantitative polymerase chain reaction.Adeno-associated virus serotype 9(AAV9)-mediated cardiac-specific GSTM1 overexpression was achieved through systemic delivery.In vitro studies employed transforming growth factor-β(TGF-β)-stimulated primary fibroblasts with siRNA/plasmid interventions.Mechanistic insights were derived from transcriptomics and lipid peroxidation assays.Results:The expression of GSTM1 in mouse CFs after MI was significantly down-regulated at both transcriptional and protein levels.In human dilated cardiomyopathy(DCM)patients with severe heart failure,GSTM1 expression was decreased alongside aggravated fibrosis.Overexpression of GSTM1 in post-MI mice improved cardiac function,while significantly reducing infarct size and fibrosis compared with the control group.In vitro models demonstrated that GSTM1 markedly attenuated collagen secretion and activation of fibroblasts,as well as suppressed their proliferation and migration.Further studies revealed that GSTM1 overexpression significantly inhibited the generation of intracellular and mitochondrial reactive oxygen species(ROS)under pathological conditions,suggesting that GSTM1 exerts an antioxidative stress effect in post-infarction fibroblasts.Further investigation of molecular mechanisms indicated that GSTM1 may suppress the initiation and progression of fibrosis by modulating lipid metabolism and ferroptosis-related pathways.Overexpression of GSTM1 significantly reduced lipid peroxidation and free ferrous iron levels in fibroblasts and mitochondria,markedly decreased ferroptosis-related indicators,and alleviated oxidative lipid levels[such as 12-hydroxyeicosapentaenoic acid(HEPE)and 9-,10-dihydroxy octadecenoic acid(DHOME)]under fibrotic conditions.GSTM1 enhanced the phosphorylation of signal transducer and activator of transcription 3(STAT3),thereby upregulating the downstream expression of glutathione peroxidase 4(GPX4),reducing ROS production,and mitigating fibroblast activation and phenotypic transformation by inhibiting lipid peroxidation.Conclusions:This study identifies GSTM1 as a key inhibitor of fibroblast activation and cardiac fibrosis,highlighting its ability to target ferroptosis through redox regulation.AAV-mediated GSTM1 therapy demonstrates significant therapeutic potential for improving outcomes post-MI.
文摘Hydrogen peroxide(H_(2)O_(2)),as a green oxidant,plays a vital role in various applications,including environmental remediation,disinfection,and chemical synthesis[1].The conventional anthraquinone process,despite its industrial maturity and high yield,suffers from high energy consumption,carbon emissions,safety risks,and reliance on precious metals[2].Despite ongoing optimizations,a more sustainable alternative is urgently needed.The direct synthesis of hydrogen peroxide from water and oxygen has long been considered as an ideal alternative due to its theoretical 100%atom efficiency and environmental sustainability.
文摘Ferroptosis, an iron-dependent type of cell death, is being considered for new clinical treatments of malignant tumors that are difficult to treat with apoptosis inducers. Although several reports have attempted to increase the sensitivity of cells to cell death by combining ferroptosis and apoptosis inducers using a single treatment, detailed elucidation of the respective mechanisms of ferroptosis and apoptosis during cell death remains unclear. Here, we evaluated combined treatment effectiveness using the apoptosis-sensitive rat insulinoma INS-1 cell lines. DNA laddering, an indicator of camptothecin (CPT)-induced apoptosis, was abolished by adding RSL3 and ML-162, but not erastin. We found that when the cells were treated with the apoptosis inducer CPT or the ferroptosis inducer RSL3, respectively, the degree of cytotoxicity observed increased dose-dependently. However, a combined CPT and RSL3 treatment did not show a synergistic decrease in cell viability. Camptothecin did not significantly affect increases in intracellular lipid peroxidation and reactive oxygen species or increases in mitochondrial and cytoplasmic free iron levels that were induced by treatment with RSL3 alone. Moreover, deferoxamine and α-tocopherol were found to inhibit RSL3-induced cytotoxicity but did not protect against CPT or CPT and RSL3-induced cytotoxicity. Finally, the exogenous addition of tert-butyl hydroperoxide inhibited DNA ladder formation that is induced by CPT, while the addition of hydrogen peroxide or ferrous ammonium sulfate had no effect. Taken together, these results suggest that lipid peroxides generated during ferroptosis may suppress cell death induced by apoptotic mechanisms.
