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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2023 · IF 9.9

Hafnium carbide nanoparticles for noninflammatory photothermal cancer therapy

Yan Ma,Haitao Wu,Qinglong Guo,Xingliang Dai,Peisan Wang,Wei Zhang,Dongdong Liu,Xulin Chen,Haisheng Qian,Xianwen Wang

Photothermal therapy (PTT) effectively suppresses tumor growth with high selectivity . Nevertheless, PTT may cause an inflammatory response that leads to tumor recurrence and treatment resistance, which are the main disadvantages of PTT. Herein, monodisperse hafnium carbide nanoparticles (HfC NPs) were successfully prepared for noninflammatory PTT of cancer. HfC NPs possessed satisfactory near-infrared (NIR) absorption, good photothermal conversion efficiency (PTCE, 36.8 %) and photothermal stability. Furthermore, holding large surface areas and intrinsic redox-active sites, HfC NPs exhibited excellent anti-inflammatory properties due to their antioxidant and superoxide dismutase (SOD) enzymatic activities . In vitro and in vivo experiments confirmed that HfC NPs converted light energy into heat energy upon NIR laser irradiation to kill cancer cells through PTT and achieved a better therapeutic effect by anti-inflammatory effects after PTT. This work highlights that multifunctional HfC NPs can be applied in noninflammatory PTT with outstanding safety and efficacy.

CAS / MDL: 12069-85-1
研究领域: 纳米技术 · 癌症治疗 · 光热疗法 · 材料科学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY · 2017 · IF 2.313

Dynamic responses of antioxidant enzymes in pearl oyster Pinctada martensii exposed to di(2-ethylhexyl) phthalate (DEHP)

Nan Xiang,Chunfeng Zhao,Xiaoping Diao,Qian Han,Hailong Zhou

Di(2-ethylhexyl) phthalate (DEHP) is recognized as one of the most ubiquitous contaminants in marine environments and causes adverse effects on the health of marine organisms. The purpose of this study was to investigate the toxic effects of DEHP on the pearl oyster Pinctada martensii . The Pinctada martensii was exposed to 0.0, 0.5, 2, 8, or 32   mg   L −1 DEHP for 7 and 10   days using parameters of antioxidant. Antioxidant indicators included levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), peroxidase (POD), and total antioxidant capacity (T-AOC) in the gills and hepatopancreas of Pinctada martensii for 7 and 10   days. Besides, we used the lowest observed effect concentration (LOEC) of five enzyme activities in different tissues of Pinctada martensii for 7 and 10   days to compare sensitivity. The results showed that the gills were more sensitive than the hepatopancreas of Pinctada martensii and that GSH activity in the gills and CAT activity in the hepatopancreas might be suitable biomarkers after 7   days of DEHP exposure. After 10   days of DEHP exposure, the GSH activity and CAT activity in the gills and SOD activity in the hepatopancreas could be regarded as biomarkers. Compared to the LOEC, GSH activity in the gills and CAT activity in the hepatopancreas after 7   days of DEHP exposure were more sensitive than any other biomarkers. In addition, after 10   days of DEHP exposure, GSH activity in the gills and hepatopancreas were much more sensitive than other activities. In conclusion, GSH activity demonstrated its potential to be used as a biomarker for the monitoring of DEHP pollution in the marine environment.

研究领域: 海洋生物学 · 环境毒理学 · 生态毒理学
✓ 已验证 DOI PubMed 高影响因子
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BIOMEDICINE & PHARMACOTHERAPY · 2019 · IF 3.743

Autophagy-endoplasmic reticulum stress inhibition mechanism of superoxide dismutase in the formation of calcium oxalate kidney stones

Juening Kang,Yan Sun,Yaoliang Deng,Quan Liu,Derong Li,Yunlong Liu,Xiaofeng Guan,Zhiwei Tao,Xiang Wang

Background Nephrolithiasis is a common disease in urology, and its pathogenesis is associated with various factors. Recent studies have shown that reactive oxygen species (ROS) can promote autophagy in the formation of kidney stones and exacerbate kidney injury. Endoplasmic reticulum stress (ERS), a key factor in regulating intracellular environmental homeostasis, is also directly related to ROS production. Therefore, this study aimed to investigate the regulatory effect of superoxide dismutase (SOD) on autophagy-ERS response during the formation of calcium oxalate (CaOx) kidney stones in rats. Methods Thirty-two rats were randomly divided into four groups (n = 8): normal control group, stone model group, stone model with atorvastatin group, and stone model with diethyldithiocarbamic acid (DETC) group. Rat models of CaOx kidney stones were established by intragastric administration of 0.75 % ethylene glycol for 4 weeks. Kidney/body weight was used to assess renal enlargement. Renal function was assessed by measuring serum SOD, creatinine (CRE), and blood urea nitrogen (BUN) levels. The expression of autophagy-related proteins LC3B and BECN1 was detected through immunohistochemical staining. Meanwhile, the expression of autophagy-ERS response-related proteins LC3B, BECN1, p62, GRP78, and CHOP was detected using Western blot and RT-PCR. Renal tubular injury markers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (Kim-1) were determined through enzyme-linked immunosorbent assay. The apoptosis of renal tubular cells and the expression of their signature proteins cleaved Caspase-3, Bax and Bcl-2 were detected using Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and Western blot assays, respectively. Crystal deposition and histological tissue injury were assessed through Von Kossa staining. Results Compared with the control group, the stone model group showed higher kidney/body weight ratio; evidently higher expression of autophagy-ERS response- and apoptosis-related proteins LC3B, BECN1, GRP78, CHOP, Bax and cleaved Caspase-3; and lower levels of p62, bcl-2 protein, and SOD. The stone model group also showed higher levels of apoptosis, serum CRE, BUN, NGAL, and Kim-1, as well as considerably greater crystal deposition and renal injury, than the control group. Atorvastatin reduced the levels of autophagy-ERS response, kidney injury, and crystal deposition, but they were increased by DETC. Conclusion Enhanced SOD activity can protect the kidneys by reducing autophagy-ERS response and CaOx kidney stone formation. Atorvastatin may be a new option for the prevention and treatment of nephrolithiasis.

研究领域: 泌尿外科 · 分子生物学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2023 · IF 3.4

Integrated 16 S rRNA gene sequencing and serum metabolomics approaches to decipher the mechanism of Qingre Lidan decoction in the treatment of cholestatic liver injury

Yang Chang,Yafei Xia,Xiaojun Liu,Putian Yu,Furong Fan,Yangyang Shi,Shixin Yan,Shu Yan

Background Cholestasis is a commonly occurring disorder induced by impaired bile flow, for which there is no effective treatment so far. Qingre Lidan decoction (QRLD) is a clinically used herbal compound for the long-term treatment of bile circulation disorders arising from inflammation and obstruction in the gallbladder and bile ducts. The objective of this study was to investigate the protective effect of QRLD on cholestatic liver injury and its possible mechanism. Methods α-Naphthyl isothiocyanate (ANIT) was used to induce cholestatic liver injury in rats. Liver histopathology and serum biochemical markers were used to assess QRLD's protective impact. The possible biomarkers and mechanism of the therapeutic benefits of QRLD were investigated using a UHPLC-based Q-Exactive Orbitrap MS / MS untargeted serum metabolomics technique together with 16 S rRNA microbiota profiling. Afterwards, using RT-qPCR as well as Western Blot techniques, the expression of pertinent indicators was determined. Results The intervention effect of QRLD was stronger at medium and high dosages than at low doses, and it dramatically decreased the levels of serum biochemical markers in cholestatic rats reflecting alterations in liver function and relieving ANIT-induced abnormalities in the liver's histopathology. Serum metabolomics showed that QRLD could affect the metabolic profile of cholestatic rats, mainly related to glycerophospholipid metabolism, taurine and hypotaurine metabolism, alanine, aspartate and glutamate metabolism, and histidine metabolic pathway. Additionally, analysis of 16 S rRNA gene sequencing indicated that QRLD could moderate ANIT-induced microbiota disorders, particularly Romboutsia, Bifidobacterium, Fusicatenibacter, Prevotella_9, Prevotellaceae_NK3B31_group and Prevotella_1. Other experimental results showed that QRLD significantly upregulated the mRNA and protein expression of PPARα, CYP7A1 and NTCP in the liver, inhibited the expression of p-IκBα, p-p65 and TNFα while increasing the anti-inflammatory factor IL-10, and downregulated the expression of MDA (a peroxidation product) and D -lactic acid (an intestinal barrier indicator) while increasing the expression of SOD and GSH. Conclusions QRLD can effectively regulate endogenous metabolites and microbiota disorders in cholestatic rats that are correlated with the attenuation of inflammation and oxidative stress.

研究领域: 药理学 · 肝病学 · 代谢组学 · 微生物学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Advanced Healthcare Materials · 2024 · IF 10

Ce12V6 Clusters with Multi-Enzymatic Activities for Sepsis Treatment

Di Liu,Si Sun,Huanhuan Qiao,Qi Xin,Sufei Zhou,Lingxia Li,Nan Song,Lijie Zhang,Qi Chen,Fangzhen Tian,Xiaoyu Mu,Shaofang Zhang,Jing Zhang,Meili Guo,Hao Wang,Xiao-Dong Zhang,Ruiping Zhang

Artificial enzymes, especially nanozymes, have attracted wide attention due to their controlled catalytic activity, selectivity, and stability. The rising Cerium-based nanozymes exhibit unique SOD-like activity, and Vanadium-based nanozymes always hold excellent GPx-like activity. However, most inflammatory diseases involve polymerase biocatalytic processes that require multi-enzyme activities. The nanocomposite can fulfill multi-enzymatic activity simultaneously, but large nanoparticles (>10 nm) cannot be excreted rapidly, leading to biosafety challenges. Herein, atomically precise Ce 12 V 6 clusters with a size of 2.19 nm are constructed. The Ce 12 V 6 clusters show excellent glutathione peroxidase (GPx) -like activity with a significantly lower Michaelis-Menten constant (K m , 0.0125 mM versus 0.03 mM of natural counterpart) and good activities mimic superoxide dismutase (SOD) and peroxidase (POD). The Ce 12 V 6 clusters exhibit the ability to scavenge the ROS including O 2 ·− and H 2 O 2 via the cascade reactions of multi-enzymatic activities. Further, the Ce 12 V 6 clusters modulate the proinflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) and consequently rescue the multi-organ failure in the lipopolysaccharide (LPS)-induced sepsis mouse model. With excellent biocompatibility, the Ce 12 V 6 clusters show promise in the treatment of sepsis.

研究领域: 纳米技术 · 生物化学 · 药理学 · 免疫学 · 医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2018 · IF 3.974

Ecotoxicity of Caenorhabditis elegans following a step and repeated chronic exposure to tetrabromobisphenol A

Fuwen Liu,Waqas Qamar Zaman,Hongjiang Peng,Chao Li,Xue Cao,Kai Huang,Changzheng Cui,Wei Zhang,Kuangfei Lin,Qishi Luo

To better understand the toxicity of tetrabromobisphenol A (TBBPA), its effects on the model nematode Caenorhabditis elegans were investigated. Following a step and repeated chronic exposure from L4-larvae to day-10 adult, physiology endpoints (growth and locomotion behaviors including head thrashes, body bends and pumping rate), biochemical endpoints (reactive oxygen species, superoxide dismutase activity, catalase activity), and molecular stress-related gene expression were tested at environmentally relevant concentrations of TBBPA (0.01–100 µg/L). The results showed that concentrations of TBBPA greater than 10 µg/L, clearly influenced the physiology behaviors (growth and locomotion endpoints). Under repeated exposure, C. elegans exhibited adaptive responses in head thrashes and pumping rate. Compared to toxicity evaluation following repeated chronic exposure, a significantly greater response was induced at the same concentration following a step chronic exposure. Reactive oxygen species production was significantly enhanced following a step and repeated TBBPA exposure at the concentrations of 1 and 10 µg/L, respectively. qRT-PCR showed that ctl-1 , ctl-2 , ctl-3 and sod-3 expression significantly increased, which was obviously correlated with physiological and biochemical behaviors under both treatment conditions according to Pearson correlation test analysis. sod-3 and ctl-2 mutations were more sensitive than the wild-type N2 under a step chronic TBBPA exposure at a level of 10 µg/L. Thus, chronic exposure to TBBPA induces an oxidative stress response in C. elegans , with ctl-2 and sod-3 playing a vital role in TBBPA-induced toxicity in nematodes.

CAS / MDL: 79-94-7
研究领域: 环境毒理学 · 分子生物学 · 遗传学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food Bioscience · 2024 · IF 4.8

A novel neuroprotective peptide against cognitive disorder in mice by regulating hippocampal oxidative stress and synaptic plasticity

Zhiqiang Lu,Yuan Gao,Zhijie Bao,Songyi Lin

The peptide Ser-Phe-Gly-Asp-Ile (SFGDI), derived from sea cucumber, has demonstrated neuroprotective effects in cell models; however, the in vivo neuroprotective efficacy of SFGDI remains unexplored. In this study, we utilized a cognitive disorder mouse model induced by scopolamine and observed that daily oral administration of SFGDI at a dosage of 40 mg/kg resulted in improved behavioral performance in the Passive avoidance test, the Channel-type water maze test, and the Novel object recognition test (P < 0.05). Furthermore, our investigation into the underlying neuroprotective mechanisms of SFGDI revealed that it reduced oxidative stress levels through the activation of the Sirt3/SOD/ROS pathway, thereby balancing hippocampal unsaturated lipids (P < 0.05) in the mouse hippocampus. Moreover, SFGDI significantly decreased hippocampal neuroinflammation by modulating the activation of microglia and hypertrophy of astrocytes. Additionally, SFGDI was found to enhance synaptic plasticity in the mouse hippocampus by activating the ChAT/p-CaMKⅡ/BDNF pathway and increasing spine density in neuron cells (P < 0.05), particularly mushroom spines (P < 0.05). These experiments demonstrate that SFGDI exhibits neuroprotective effects by regulating hippocampal oxidative stress through the Sirt3/SOD/ROS pathway and synaptic plasticity via the ChAT/p-CaMKⅡ/BDNF pathway in the mouse hippocampus, thus emerging as a potential neuro-nutraceutical agent for alleviating memory impairment.

CAS / MDL: 51-34-3
研究领域: 神经科学 · 药理学 · 分子生物学
✓ 已验证 产品关联 DOI 高影响因子
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Journal of Materials Chemistry B · 2020 ·Vol. 8 ·期 11 ·2321-2330 · IF 5.344

Carbon dot targeting to nitrogen signaling molecules for inhibiting neuronal death

Lufei Ouyang,Xiaoyu Mu,Junying Wang,Qifeng Li,Yalong Gao,Haile Liu,Si Sun,Qinjuan Ren,Ruijuan Yan,Jingya Wang,Qiang Liu,Yuanming Sun,Changlong Liu,Hua He,Wei Long,Xiao-Dong Zhang

Free radical-induced oxidative damage and nitrosative stress have been identified as key factors in neuroinflammation responses after traumatic brain injury (TBI), with which reactive oxygen and nitrogen species (RONS), especially nitrogen signaling molecules, are strongly associated. Here, we prepared ultrasmall carbon dot (CD) by using a simple and facile method. In vitro assessment experiments show that the antioxidative CD exhibits an ultrahigh target-scavenging effect for nitrogen signaling molecules, especially the highly reactive ˙NO and ONOO−. However, CD can only partially eliminate conventional oxygen radials such as O2˙− and ˙OH, indicating CD has a preference for RNS modulation. Moreover, in vitro cell experiments and in vivo mice experiments reveal that CD can reduce the reactive oxygen species (ROS) level and lipid peroxidation, enhance superoxide dismutase (SOD) activity and GSSG level, and further improve the survival rate of neuron cells and TBI mice. These results declare that antioxidative CD could serve as an effective therapeutic for TBI.

研究领域: 神经科学 · 药理学 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANNALS OF AGRICULTURAL SCIENCE · 2023 · IF 5.9

CUT&tag-seq analysis of heat stress response in broiler liver provides novel insights into the improved thermotolerance by dietary phloretin

Hong Hu,Liang Chen,Ying Huang,Kunping Wang,Xi Bai,Hongbin Pan

This work aimed to study the effect of phloretin on antioxidant profiles through nuclear factor erythroid 2–related 2 (Nrf2)-DNA interactions in the liver of heat-stressed broilers by Cleavage Under Targets and Tagmentation combined with high-throughput sequencing (CUT&Tag-seq). One hundred and sixty 22-day-old Arbor Acres broilers were divided into four groups: a normal temperature group (NT: 22.8–23.4 °C and 46–55.8 % humidity) was fed a basal diet and three high temperature groups (China Summer condition: 29.7–31.7 °C and 77.9–94.8 % humidity) were fed the basal diet supplemented with 0 (HT group), 100 mg/kg (LT group) and 200 mg/kg (PT group) phloretin. Liver samples were taken from 42-day-old broilers. High temperature condition increased ( P  ≤ 0.05) the malondialdehyde (MDA) level, but decreased ( P  ≤ 0.05) the activities and mRNA expression levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and Nrf2. Dietary 200 mg/kg phloretin decreased ( P  ≤ 0.05) the MDA level, but increased ( P  ≤ 0.05) the activities and mRNA expression levels of GSH-Px, SOD, CAT and Nrf2 in the liver of heat-stressed broilers. CUT&Tag-seq showed that 4042 DEPs were up-regulated, while 2322 DEPs were down-regulated in the PT group compared with the HT group. The Nrf2-binding gene of DEPs contained SOD3, CAT, SOD2, and p38 mitogen-activated protein kinase. Most TOP20 significant KEGG pathways were associated with “Environmental Information Processing”. Summary, phloretin could improve oxidative damage by Nrf2 and its downstream DNA-sites including genes and Nrf2-bingding non-coding RNAs in the liver of heat-stressed broilers.

CAS / MDL: 60-82-2
研究领域: 动物科学 · 分子生物学 · 基因组学 · 生物信息学
✓ 已验证 产品关联 DOI 高影响因子
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INFLAMMATION · 2020 ·Vol. 43 ·期 5 ·1751-1758 · IF 3.212

Protective Effects of SIRT6 Against Inflammation, Oxidative Stress, and Cell Apoptosis in Spinal Cord Injury

Zhaohui Chen,Shuihua Wu

Accumulating evidence supports that Sirtuin 6 (SIRT6) may play a vital role in the pathogenesis of spinal cord injury. The current study was designed to investigate the specific effects of SIRT6 on spinal cord injury (SCI). HE and Nissl staining were performed for pathological analysis in SCI rats. SIRT6 expression was detected by RT-qPCR. CCK8 assay was applied for the detection of cell viability of LPS-injured PC12 cells. TNF-a, IL-1β, IL-6, MCP-1 levels and ROS, MPO, SOD levels were assessed to evaluate inflammation and oxidative stress in spinal cord injury. Cell apoptosis were evaluated by morphological examination using AO/EB fluorescent staining methods and key proteins related to apoptosis were explored via western blot. HE staining revealed increased cavity involving the dorsal white matter and central gray matter, and Nissl staining discovered the loss of motor neurons in the ventral horn in SCI rats. SIRT6 had lower expression in SCI rats. Lipopolysaccharide (LPS) exposure induced cell apoptosis and reduced the expression of SIRT6. Mechanistically, we revealed that up-regulation of SIRT6 alleviated inflammation and oxidative stress and inhibited cell apoptosis in spinal cord injury. Together, our findings indicated that SIRT6 attenuated spinal cord injury by suppressing inflammation, oxidative stress, and cell apoptosis. This study demonstrates that SIRT6 may represent a protective effect against spinal cord injury.

CAS / MDL: 10127-02-3 1239-45-8
研究领域: 神经科学 · 分子生物学 · 病理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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International Journal of Nanomedicine · 2022 · IF 7.033

Oral Administration of Therapeutic Enzyme Capsule for the Management of Inflammatory Bowel Disease

Xiao Liang,Kai Wen,Yingxuan Chen,Guangxu Fang,Shengcai Yang,Quanshun Li

Background: Oral administration of proteins/peptides is challenging in clinical application due to their instability and susceptibility in the gastrointestinal tract. Materials and methods: The in situ polymerization on the surface of enzymes was used to encapsulate antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) in polymeric shells, and the reactive oxygen species (ROS) scavenging ability was monitored based on DCFH-DA probe using flow cytometry and confocal laser scanning microscopy. The mRNA expression level of pro-inflammatory factors was assessed by real-time qPCR, using lipopolysaccharide-induced RAW264.7 cells as a model. Finally, the enzyme capsules were orally administered for the treatment of inflammatory bowel disease using dextran sodium sulfate (DSS)-induced colitis mice as a model, based on the evaluation of the disease-associated index, ROS level and pro-inflammatory cytokines' expression. Results: The enzyme capsules could effectively scavenge the intracellular reactive oxygen species (ROS) through the cascade catalysis of SOD and CAT, and thus protect the cells from ROS-induced oxidative damage. Meanwhile, the enzyme capsules could inhibit the secretion of pro-inflammatory cytokines from macrophages, thereby achieving favorable anti-inflammation effect. Oral administration of enzyme capsules could facilitate the accumulation of enzymes in the inflamed colon tissues of DSS-induced colitis mice. Moreover, the oral delivery of enzyme capsules could effectively alleviate the symptoms associated with colitis, attributing to the excellent ROS scavenging ability and the inhibition of pro-inflammatory cytokines' level. Conclusion: In summary, our findings provided a promising approach to construct enzyme-based nano-formulations with favorable therapeutic efficacy and biocompatibility, exhibiting great potential in the treatment of gastrointestinal diseases in an oral administration manner.

研究领域: 药理学 · 胃肠病学 · 纳米医学 · 炎症研究
✓ 已验证 DOI PubMed 高影响因子
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PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION · 2023 · IF 2.7

Multienzyme-Mimetic Activity of Gold/Cerium Oxide Nanozyme

Qi Xin,Li Wang,Haiyan Ruan,Ling Liu,Si Sun,Jing Zhang,Menglin Wu,Xiaoyu Mu,Hao Wang,Shaofang Zhang,Xiao-Dong Zhang

Redox-active nanozymes offer low-cost controlled synthesis, high stability, and tunable catalytic properties over natural enzymes, which have attracted wide attention in the field of disease diagnosis and treatment. However, the improvement of catalytic activity remains an important challenge for nanozymes. Herein, the Au/CeO 2 nanozymes is developed to achieve enhanced multiple enzyme-mimetic activity. The Au/CeO 2 nanozymes at 5% doping possess best peroxidase-like activity with threefold higher catalytic rate than CeO 2 . For catalase-mimic catalysis, the Au/CeO 2 nanozymes at 5% doping also exhibited a 1.5-fold enhanced reaction rate higher than pure CeO 2 . The superoxide dismutase (SOD)-like capacity of Au/CeO 2 nanozymes is proportional to Au content. The Au/CeO 2 nanozymes at 10% doping show optimal SOD-like capacity of 60.2 U mg −1 . In vitro experiments validate the regulation ability of intracellular oxidative stress and inflammation. Au/CeO 2 nanozymes can reduce lipopolysaccharide- or H 2 O 2 -induced oxidative damage by scavenging excess ROS in nerve cell. Therefore, Au/CeO 2 can be used as a promising antioxidant in disease treatment, and the study offers general guidelines for achieving enhanced biocatalytic property through atomic doping.

研究领域: 纳米技术 · 生物催化 · 疾病诊断与治疗 · 材料科学
✓ 已验证 产品关联 DOI 高影响因子
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