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Hydrophobic cellulose laurate (CL) with high degree of substitution has been successfully synthesized. The mechanical property, water-resistance, antimicrobial activity, barrier properties and food decontamination of cellulose-laurate-curcumin films (CL-Cu x , x = 0.1, 0.5, and 1) were investigated. The results showed that the mechanical properties of CL-Cu x hardly change after soaking in water for 24 h, probably due to the strong hydrophobicity of cellulose laurate. CL-Cu 1 represented a good photoinduced antibacterial effect against S. aureus. After irradiation of white light at 60 mW·cm−2 for 20 min, the inhibition efficiency reached to 95 ± 2.02%, probably owing to the generated active 1O 2. In comparison with CL-Cu 1 stored in natural light, the bacteriostatic effect of CL-Cu 1 in dark storage was better, and the inhibition rate of CL-Cu 1 remained 80 ± 1.22 at 60th day. The stabler excited state of curcumin in hydrophobic cellulose laurate was probably assigned to inhibition of tautomerism or conformational transition, which was beneficial to the generation of singlet oxygen. CL-Cu 1 can significantly inhibit the growth of TVBN and TVC values of chilled meat upon white light irradiation, indicating the potential application of cellulose-laurate-curcumin films in food decontamination. [Display omitted] [ABSTRACT FROM AUTHOR]

Studies have indicated that glutamate receptor subunit 3 peptide B antibodies (GluR3B Ab’s) by directing against a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype glutamate receptors (AMPARs) subunit 3 (GluR3B) was involved in the hippocampal neuron damage in the pathogenesis of epilepsy. Glutamate accumulation is critical for oligodendrocyte precursors (OPCs) excitotoxic injury. However, remarkably little is known about whether GluR3B Ab’s causes OPCs excitotoxicity, and the underlying mechanisms remain unclear. In this study, we found that the survival rate of OPCs decreased, apoptosis increased and the release of LDH increased with GluR3B Ab’s treatment. GluR3B Ab’s enhanced the level of intracellular Ca 2+ and reactive oxygen species (ROS), caused mitochondrial potential collapse measured by JC-1 and promoted mitochondrial cytochrome C release. AMPARs antagonist NBQX reversed OPCs apoptosis caused by GluR3B Ab’s. Taken together, these data suggests that AMPAR was involved in GluR3B Ab’s-induced OPCs toxicity by mitochondrial dysfunction. The study revealed a new mechanism for OPCs excitotoxicity in many central nervous system diseases such as epilepsy. [ABSTRACT FROM AUTHOR]

3-monochloro-1,2-propanediol (3-MCPD) is a food contaminant believed to be harmful to human health. Previous studies showed that 3-MCPD exerts toxic effects in multiple tissues, but whether 3-MCPD affects female reproductive function remained unknown. Here, using mouse gastric lavage models, we report that 3-MCPD exposure for four weeks affected body growth, decreased the ovary/body weight ratio, and increased atretic follicle numbers. Expression levels of follicular development-related factors decreased. Further studies found that ovaries from 3-MCPD exposed mice had activated the Transforming Growth Factor-β (TGF-β) signaling pathway and promoted ovarian fibrosis. Increased TNF-α, IL-1 and NF-κB expression also indicated the occurrence of ovarian inflammation. Exposure to 3-MCPD stimulated the caspase pathway and enhanced granulosa cell apoptosis. Consistent with disrupted ovarian homeostasis, 3-MCPD exposure interfered with mitochondrial function, generated more reactive oxygen species, increased ferrous ion and lipid peroxidation levels, and resulted in decreased oocyte development potential. Collectively, these findings indicated that 3-MCPD exposure induced ovarian inflammation and fibrosis, and caused disorders of mitochondrial function and ferrous ion homeostasis in oocytes, which consequently disturbed follicle maturation and reduced oocyte quality. [Display omitted] • 3-MCPD exposure impaires mouse follicular development. • 3-MCPD exposure induces ovary fibrosis, inflammation and apoptosis. • 3-MCPD exposure decrease oocyte quality through oxidative stress. [ABSTRACT FROM AUTHOR]

• Cu metal deposition on the ZnO can provide more surface oxygen free radicals. • Cu metal increase the binding energy of HCHO to Cu-modified ZnO. • Cu metal can effectively improve the performance of ZnO for HCHO detection. • Cu-modified ZnO displaying the excellent endurance to humidity. • Mechanism of Cu-modified ZnO gas sensor was studied by first-principles calculation. Based on Cu-modified ZnO (CZO), a highly sensitive gas sensor for formaldehyde (HCHO) detection at room temperature was prepared by the sol–gel method, and the sensing mechanism was studied by density functional theory. Calculations indicate that the binding energy of CZO to HCHO is higher than that of pure ZnO when Cu metal occupies the oxygen vacancy on the surface of ZnO, which is beneficial for CZO to capture more HCHO molecules. Moreover, Cu metal splits oxygen molecules in the air to form a large number of oxygen free radicals on the surface of CZO and react with HCHO molecules. The lowest band gap can be obtained when HCHO is adsorbed in CZO compared to other gases, which means CZO has better selectivity in the detection for HCHO. Experiments show that Cu metal can effectively improve the performance of ZnO for HCHO detection. CZO with 3 mol% Cu exhibits short response/recovery times (1.7 s/2.9 s) and the limit of detection (LOD) is 0.61 ppm at HCHO concentration of 1 ppm. Moreover, CZO displays the excellent endurance to humidity. Such a metal-modified ZnO offers great potential for the development of highly sensitive gas sensor for HCHO detection. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) caused by high glucose (HG) is involved in a lot of diseases including diabetes. However, the underlying mechanism of ROS induction by HG remains unclear. Emerging evidence has shown the 8-oxoguanine glycosylase (OGG1) is the main DNA glycosylase responsible for atherosclerosis, obesity, hepatic steatosis, and insulin resistance, and so on. Our aim was to explore the role of OGG1 on HG-mediated endothelial ROS. Human umbilical vein endothelial cells (HUVECs) were exposed to HG (30 mM) for different time periods. HG predominantly inhibited OGG1 expression in a time-dependent manner measured by western blotting, qPCR and immunofluorescence. Additionally, HUVECs were cultured with a fluorescent probe, DCFH and DHE, after being subjected to HG. Cell chemiluminescence and flow cytometry results revealed that HG caused endothelial ROS activation. High glucose remarkably decreased endothelial OGG1 expression. The overexpression of OGG1 significantly reversed HG-mediated PKC and NADPH oxidase activities and ROS levels. Moreover, manipulated expression of PKC significantly contacted the role of OGG1 on NADPH oxidase activation. These results suggest that OGG1 downregulation promoted HG-induced endothelial ROS production and might be a potential clinical treatment target of diabetics. [ABSTRACT FROM AUTHOR]

This study aims to clarify the specific anti-fatigue components of Schizophyllum commune (S.commune) and analyze its potential anti-fatigue mechanism. The main anti-fatigue active ingredient of S.commune was locked in n-butanol extract (SPE-n) by activity evaluation. Twelve compounds were identified by high performance liquid chromatography-electrospray tandem mass spectrometry (LC–ESI–MS/MS). The anti-fatigue effect of morusin is the most predominant among these 12 ingredients. The determination of biochemical indices showed that morusin could increase liver glycogen reserves, improve the activity of antioxidant enzymes in liver, and reduce reactive oxygen species (ROS) content in muscle tissue, thereby reducing myocyte damage. Further studies revealed that morusin could reduce the level of oxidative stress by activating Nrf2/HO-1 pathway, thus alleviating the fatigue of mice caused by exhaustive exercise. The current findings provide a theoretical basis for the development of natural anti-fatigue functional food. [Display omitted] • The anti-fatigue active components was mainly n-butanol extract of Schizophyllum commune through activity screening. • Morusin was identified as the major active anti-fatigue substance in Schizophyllum commune by LC–ESI–MS/MS. • Morusin could relieve fatigue by regulating the Nrf2/HO-1 pathway and down-regulating oxidative stress. [ABSTRACT FROM AUTHOR]

Coronary heart disease (CHD) is a chronic disease that seriously threatens people's health and even their lives. Currently, there is no ideal drug without side effects for the treatment of CHD. Trichosanthis Pericarpium (TP) has been used for several years in the treatment of diseases associated with CHD. However, there is still a need for systematic research to unravel the pharmacodynamic substances and possible mechanism of TP in the treatment of coronary heart. The purpose of current study was to explore the pharmacodynamic substances and potential mechanisms of TP in the treatment of CHD via integrating network pharmacology with plasma pharmacochemistry and experimental validation. The effect of TP intervention in CHD was firstly assessed on high-fat diet combined with isoprenaline-induced CHD rats and H 2 O 2 -induced H9c2 cells, respectively. Then, the LC-MS was utilized to identify the absorbed components of TP in the plasma of CHD rats, and this was used to develop a network pharmacology prediction to obtain the possible active components and mechanisms of action. Molecular docking and immunohistochemistry were used to explore the interaction between TP and key targets. Subsequently, the efficacy of the active ingredients was investigated by in vitro cellular experiments, and their metabolic pathways in CHD rats were further analyzed. The effects of TP on amelioration of CHD were verified by in vivo and in vitro experiments. Plasma pharmacochemistry and network pharmacology screened six active components in plasma including apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin. The interaction of these compounds with potential key targets AKT1, IL-1β, IL-6, TNF-α and VEGFA were preliminarily verified by molecular docking. And immunohistochemical results showed that TP reduced the expression of AKT1, IL-1β, IL-6, TNF-α and VEGFA in CHD rat hearts. Then cellular experiments confirmed that apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin were able to reduce the ROS level in H 2 O 2 -induced HUVEC cells and promote the migration and tubule formation of HUVEC cells, indicating the pharmacodynamic effects of the active components. Meanwhile, the metabolites of TP in CHD rats suggested that the pharmacological effects of TP might be the result of the combined effects of the active ingredients and their metabolites. Our study found that TP intervention in CHD is characterized by multi-component and multi-target regulation. Apigenin, phenylalanine, linoleic acid, quercetin, luteolin, and tangeretin are the main active components of TP. TP could reduce inflammatory response and endothelial damage by regulating AKT1, IL-1β, IL-6, TNF-α and VEGFA, reduce ROS level to alleviate the oxidative stress situation and improve heart disease by promoting angiogenesis to regulate endothelial function. This study also provides an experimental and scientific basis for the clinical application and rational development of TP. [Display omitted] [ABSTRACT FROM AUTHOR]

Zanthoxylum armatum DC. (ZADC) is a traditional medicinal plant with various pharmacological activities and is widely used in China, Japan, India, and other regions. Previous studies have revealed that the methanol extract of ZADC can cause neurotoxicity symptoms in rats, such as drooling, decreased appetite, decreased movement, and increased respiratory rate. However, the basis of these toxic substances and the mechanism of neurotoxicity remain unclear. To evaluate the effects of ZADC on nerve cells and their damage mechanisms and discuss the possible toxic substance basis. The ethyl acetate extract of ZADC is obtained by extracting the methanol extract of ZADC with ethyl acetate. The Q-Orbitrap LC-MS/MS method was employed to analyze the chemical composition of the EA extract of ZADC. SH-SY5Y cells were incubated with different concentrations of the ethyl acetate extract of ZADC. The cytotoxicity of the extract was evaluated using CCK-8, LDH, and ROS assays, and the oxidative stress status of cells was assessed using MDA, GSH, and SOD. Cell apoptosis was detected using flow cytometry. Damage to mitochondrial function was evaluated by labeling mitochondria, ATP, and MMP with fluorescence. Cyto-C, Caspase-3, Caspase-9, Apaf-1, Bax, and reduced Bcl2 expression were measured to evaluate the activation of the mitochondrial apoptosis pathway. Finally, NAC intervention was used to detect changes in the relevant indicators. The activation of mitochondrial apoptosis pathway was evaluated by measuring Cyto-C, Caspase-3, Caspase-9, Apaf-1, and Bax and Bcl2 expression. Finally, NAC intervention was utilized to detect changes in the relevant indicators. After treating SY-SY5Y cells with EA extract from ZADC, cell viability decreased significantly, and the intracellular ROS level increased in a dose-dependent manner. Meanwhile, ZADC can cause cellular oxidative stress and increase MDA and SOD concentrations while decreasing GSH concentrations. It can also shorten the mitochondrial cristae and decrease the number of mitochondria. In contrast, it can reduce ATP synthesis in the mitochondria and mitochondrial membrane potential (MMP). Furthermore, it increased the apoptosis rate and the expression of Cyto-C, Caspase-3, Caspase-9, Apaf-1, and Bax and reduced Bcl2 expression. NAC intervention alleviated the reduction in SH-SY5Y cell survival and the accumulation of reactive oxygen species induced by the EA extract in ZADC. It also inhibits signaling pathways dominated by proteins, such as Cyto-C, reducing cell apoptosis and cytotoxicity. A total of 46 compounds were identified in the extracts. The results suggest that EA extract of ZADC can induce the mitochondrial apoptotic pathway by accumulating ROS in cells, leading to apoptosis. Antioxidants had a good inhibitory and protective effect against cell damage caused by the EA extract of ZADC. The neurotoxic components of ZADC may be organic acids and compounds containing amino groups. [Display omitted] • Zanthoxylum armatum DC. induces cell apoptosis and produces neurotoxicity. • Zanthoxylum armatum DC. causes intracellular ROS accumulation and oxidative stress. • ROS mediated mitochondrial apoptosis pathway is the main mechanism of ZADC toxicity. • NAC intervention can alleviate the neurotoxicity caused by Zanthoxylum armatum DC. [ABSTRACT FROM AUTHOR]

Qing Gan Zi Shen Decoction (QGZS) is a traditional Chinese formula. It has been extensively used for decades in the treatment of hypertension combined with metabolic diseases, but its cardioprotective effects and underlying mechanisms are poorly understood. To explore the cardioprotective effects and potential mechanisms of QGZS in an animal model of obese hypertension. In this study, spontaneously hypertensive rats (SHRs) were utilized as an animal model to examine the effects of a high-fat diet and two concentrations of QGZS. Echocardiography, hematoxylin eosin (H&E) staining, and wheat germ agglutinin (WGA) staining were employed to assess the cardiac structure and function of the SHRs throughout a 16-week therapy period. Furthermore, Western blotting (WB) and immunofluorescence (IF) were employed to identify the levels of Nrf2 expression in the mitochondria, cytoplasm, and nucleus of the myocardium. Additionally, transmission electron microscopy and enzyme-linked immunosorbent assay (ELISA) were utilized to measure mitochondrial morphology and pro-inflammatory cytokine levels, respectively. Furthermore, Western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) techniques were employed to quantify the levels of marker proteins associated with myocardial fibrosis, cardiac inflammation, oxidative stress, and mitochondrial dysfunction. QGZS inhibited weight gain and depressed systolic and mean arterial pressures in high-fat-fed SHRs. Echocardiographic results demonstrated that QGZS prevented the increase in left ventricular mass, restricted the growth of left ventricular diameter, and improved ejection fraction (EF), fractional shortening (FS), and the ratio of early diastolic peak velocity of transmitral flow (E) to late diastolic peak velocity (A) in high-fat-fed SHRs. This suggested that QGZS prevented ventricular remodeling and protected cardiac systolic and diastolic functions. H&E and WGA staining showed that QGZS improved cardiomyocyte disorders and restricted cardiomyocyte hypertrophy. The underlying mechanisms, QGZS attenuated the oxidative stress state, including reducing the generation of reactive oxygen species (ROS) in the myocardium, revitalizing the antioxidant enzyme system, and protecting mitochondrial function. Moreover, QGZS alleviated the pro-inflammatory state in high-fat-fed SHRs. What's more, QGZS significantly increased the expression level of Nrf2 in nuclei and mitochondria in rat heart tissues, exerting a proximate Nrf2 agonist effect. QGZS exerted cardioprotective effects, in part due to its increasing expression of Nrf2 protein in the heart, which promoted Nrf2 nuclear expression. [Display omitted] • In high-fat-induced obese SHRs, Qing Gan Zi Shen reversed ventricular remodeling and protected cardiac function. • In high-fat-induced obese SHRs, Qing Gan Zi Shen alleviated ventricular remodeling and myocardial fibrosis. • QGZS actived Nrf2 to play a role in reducing cardiac inflammation, inhibiting cardiac oxidative stress, and protecting mitochondrial function. [ABSTRACT FROM AUTHOR]

The synthesized core–shell coordination s-Fe0@Cu-Pd trimetal catalyst could effectively activate room-temperature dissolved ambient oxygen and realized synergistic catalytic degradation of composite pollutants including TC and PNP. [Display omitted] • s-Fe0@Cu-Pd trimetal was synthesized via a step displacement plating process. • s-Fe0@Cu-Pd trimetal sample had the strongest oxidation and reduction ability. • s-Fe0@Cu-Pd trimetal sample presented the strongest O 2 activation ability. • There was a synergistic catalysis effect for wrapped Cu and Pd on s-Fe0@Cu-Pd. Room-temperature ambient air is cheap and easy to obtain, hence the application of room-temperature ambient air as sole oxidant for pollutant degradation is extremely fascinating. In this work, core–shell coordination sponge-Fe0@Cu-Pd trimetal catalyst was synthesized via a simple step displacement plating process employing first displacement of Cu and the subsequent displacement of Pd, and applied as heterogeneous catalyst for synergistic catalytic degradation of composite pollutants including TC and PNP. The prepared s-Fe0@Cu-Pd trimetal sample was characterized with XRD, SEM, TEM, VSM and XPS. The characterization results revealed the obtained s-Fe0@Cu-Pd trimetal sample was a 20 ∼ 30 nm core–shell spherical morphology composed of Fe0 aggregates core wrapped by a Cu-Pd shell layer. The obtained sponge-Fe0@Cu-Pd trimetal catalyst could efficiently activate room-temperature dissolved ambient oxygen and achieve the largest TC removal rate of 99.08 % and PNP removal rate of 97.16 % as well as the biggest removal rate constant of 8.76 min−1 for TC degradation and 7.55 min−1 for PNP degradation within 60 min at experimental conditions: [TC] = 30 mg/L, [PNP] = 30 mg/L, [Catalyst] = 25.52 g/L, pH = 3, 298 K ascribed to the strongest oxidation and reduction ability confirmed by CV characterizations, the lowest charge transfer and contact resistance affirmed by EIS measurements, the strongest O 2 activation ability verified by O 2 -TPD characterizations and DFT analyses, the largest external surface area and mesoporous volume validated by Nitrogen adsorption and desorption characterizations as well as the synergistic catalysis effect for wrapped Cu and Pd. Quenching experiments and EPR characterizations revealed that •OH, •O 2 −, 1O 2 and •H are all the reactive species and meanwhile •O 2 − served as the main reactive oxygen species. Furthermore, possible mechanisms of TC and PNP degradation via sponge-Fe0@Cu-Pd trimetal catalyst were proposed. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancer causes countless deaths every year due to therapeutic resistance. However, whether metabolic alterations contribute to chemoresistance is not well understood. In this study, we report that fatty acid (FA) catabolism was activated in gastrointestinal cancer cells treated with oxaliplatin, which exhibited higher expression of the rate-limiting enzymes carnitine palmitoyltransferase 1B (CPT1B) and CPT2. The clinical analysis also showed that high expression of these enzymes was associated with poor oxaliplatin-based chemotherapy outcomes in patients. Furthermore, genetic or pharmacological inhibition of CPT2 with perhexiline disturbed NADPH and redox homeostasis and increased reactive oxygen species (ROS) generation and cell apoptosis in gastrointestinal cancer cells following oxaliplatin treatment. Specifically, the combination of oxaliplatin and perhexiline significantly suppressed the progression of gastrointestinal cancer in cell-based xenograft and patient-derived xenograft (PDX) models. Mechanistically, CPT2 was transcriptionally upregulated by nuclear factor of activated T cells 3 (NFATc3), which translocated to the nucleus in response to oxaliplatin treatment. In summary, our study suggests that the inhibition of CPT-mediated FA catabolism combined with conventional chemotherapy is a promising therapeutic strategy for patients with gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

A new polysaccharide fraction (CCPP-1) was obtained from Craterellus cornucopioides . CCPP-1 had an average molecular weight of 9.2 × 10 5  Da, which was mainly composed of mannose, glucose, xylose, arabinose, fructose in molar ratio of 0.7:0.05:0.18:1:0.05. Results of structural characterization revealed that the dominant linkage types of CCPP-1 were →3, 6)-Man p (1→, T-Ara f , →4, 6)-Man p (1→, →5)-Ara f (1→ and →3)-Ara f (1→. Interesting, in vitro antioxidant activities assays showed that CCPP-1 possessed strong scavenging abilities on DPPH and ABTS radicals. The oxidative hemolysis induced by AAPH in mice erythrocytes was effectively reversed by incubation with CCPP-1. CCPP-1 significantly prevented AAPH-induced intracellular reactive oxygen species (ROS) generation. Moreover, CCPP-1 could significantly restore AAPH-induced increase of intracellular antioxidant enzyme glutathione peroxidase (GPx) and catalase (CAT) activities to normal level, as well as inhibit intracellular malondialdehyde (MDA) formation. Therefore, CCPP-1 could protect against AAPH-induced oxidative-stress in erythrocytes, which would be explored as naturally potential antioxidant agent applied in food and cosmetic fields. [ABSTRACT FROM AUTHOR]

Chloroacetonitrile (CAN) is a halogenated acetonitrile often produced while disinfecting drinking water. Previous studies have shown that maternal exposure to CAN interferes with fetal development; however, the adverse effects on maternal oocytes remain unknown. In this study, in vitro exposure of mouse oocytes to CAN reduced maturation significantly. Transcriptomics analysis showed that CAN altered the expression of multiple oocyte genes, especially those associated with the protein folding process. CAN exposure induced reactive oxygen species production, accompanied by endoplasmic reticulum (ER) stress and increased glucose regulated protein 78, C/EBP homologous protein and activating transcription factor 6 expression. Moreover, our results indicated that spindle morphology was impaired after CAN exposure. CAN disrupted polo-like kinase 1, pericentrin and p-Aurora A distribution, which may be an origin inducer that disrupts spindle assemble. Furthermore, exposure to CAN in vivo impaired follicular development. Taken together, our findings indicate that CAN exposure induces ER stress and affects spindle assembly in mouse oocytes. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Methane has been reported to play a protective role in ischemia-reperfusion injury via anti -oxidation, anti-inflammatory and anti-apoptotic activities. This study was designed to determine the protective effects of methane-rich saline (MRS) on acute carbon monoxide (CO) poisoning. Methods A total of 36 male Sprague-Dawley rats were randomly divided into 3 groups: sham group, CO group and MRS group. Acute CO poisoning was induced by exposing rats to 1000 ppm CO in air for 40 min and then to 3000 ppm CO for an additional 20 min until they lost consciousness. MRS at 10 ml/kg was intraperitoneally administered at 0 h, 8 h and 16 h after CO exposure. Rats were sacrificed 24 h after CO exposure. Brains were collected for Nissl staining. The cortex and hippocampus were separated for the detections of malondialdehyde (MDA), 3-nitrotyrosine (3-NT), 8-hydroxydeoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), interleukin1-β (IL-1β), interleukin-6 (IL-6) and superoxide dismutase (SOD) activities. Results The results showed that MRS treatment improved neuronal injury, reduced MDA, 3-NT and 8-OHdG, and increased SOD activity of the hippocampus and cortex compared with normal saline-treated rats. In addition, MRS reduced the expression of TNF-α and IL-1β in the brain but had no effect on IL-6 expression. Conclusion These findings suggest that MRS may protect the brain against acute CO poisoning-induced injury via its anti -oxidative and anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

Alterations in protein ubiquitination and hypoxia-inducible factor (HIF) signaling both contribute to tumorigenesis and tumor progression. Ubiquitination is a dynamic process that is coordinately regulated by E3 ligases and deubiquitinases (DUBs), which have emerged as attractive therapeutic targets. HIF expression and transcriptional activity are usually increased in tumors, leading to poor clinical outcomes. Reactive oxygen species (ROS) are upregulated in tumors and have multiple effects on HIF signaling and the ubiquitin system. A growing body of evidence has shown that multiple E3 ligases and UBDs function synergistically to control the expression and activity of HIF, thereby allowing cancer cells to cope with the hypoxic microenvironment. Conversely, several E3 ligases and DUBs are regulated by hypoxia and/or HIF signaling. Hypoxia also induces ROS production, which in turn modulates the stability or activity of HIF, E3 ligases, and DUBs. Understanding the complex networks between E3 ligase, DUBs, ROS, and HIF will provide insights into the fundamental mechanism of the cellular response to hypoxia and help identify novel molecular targets for cancer treatment. We review the current knowledge on the comprehensive relationship between E3 ligase, DUBs, ROS, and HIF signaling, with a particular focus on the use of E3 ligase or DUB inhibitors in cancer. [ABSTRACT FROM AUTHOR]

Herein, using manganese dioxide octahedral molecular sieve (Mn-OMS) as the catalyst, we investigate how pollutant electron property affects the peroxymonosulfate (PMS) activation mechanism. More than 95% of electron-rich pollutants are degraded in the Mn-OMS/PMS system after 30 min reaction time, but oxidative decomposition of electron-poor pollutants takes at least 150 min. This difference in reaction rate is proved to be pollutant-dependent. We then combine multiple methods to cross-validate the PMS activation mechanism, including the quenching test, EPR characterization, solvent-exchange experiment, PMS decomposition rate test, and electrochemical analysis. Catalyst-mediated electron transfer is determined as the main activation mechanism for electron-rich pollutants degradation, while removal of electron-poor pollutants relies on singlet oxygen (1O 2) and/or radicals. Additionally, the PMS activation mechanism depends on whether H 2 O or pollutants or low-valence Mn ions preferentially transfer electrons to the adsorbed PMS. This work provides mechanistic insights into the effect of pollutants type on PMS activation. [Display omitted] • Pollutant type can induce the transformation of PMS activation mechanism. • Water molecules are indispensable reactants in singlet oxygen generation. • The sources of singlet oxygen are water molecules and peroxides. [ABSTRACT FROM AUTHOR]

Polysaccharides from edible fungi usually exhibit many bioactivities. Our previous studies found that polysaccharide TLH-3 extracted from Tricholoma lobayense possessed noticeable antioxidant activity. To further explore its biological activities, the antioxidant and anti-aging activities of TLH-3 were evaluated in vitro and in vivo . The results of antioxidant activity in vitro showed that TLH-3 could enhance the cell viability, reduce the production of reactive oxygen species (ROS) and inhibit oxidative damage induced by tert -butylhydroperoxide ( t -BHP) in human embryonic lung fibroblasts (HELF) cells. The anti-aging capability was measured in d -galactose ( d -gal)-induced aged mice model, and the experimental data showed that TLH-3 significantly inhibited the formation of malondialdehyde (MDA) and raised the activities of superoxide dismutase (SOD) and catalase (CAT) in mice liver and serum ( p < 0.05). This study suggested that TLH-3 possessed apparent antioxidant and anti-aging activities and could be exploited as a potent dietary supplement to attenuate aging and prevent age-related diseases in humans. [ABSTRACT FROM AUTHOR]

[Display omitted] • The genotoxicity of TiO 2 NPs was confirmed at the single-cell level. • CINP, RPA3, and PRKACA served as biomarkers of TiO2 NPs exposure. • 5 nm and 14 nm TiO 2 NPs caused a response similar to antivirus defense. • Unique gene expression patterns were found within the same exposure of TiO2 NPs. Titanium dioxide nanoparticles (TiO 2 NPs) have attracted substantial attention in various applications, including environmental remediation and nanomedicine. A detailed understanding of the toxicity of TiO 2 NPs and the underlying mechanisms is fundamental to further development of their environmental and biomedical applications. Herein, we determined the changes in the transcriptional profile of human bone marrow stromal cells (BMSCs) after a set of different sized TiO 2 NPs exposure using single-cell RNA-seq (scRNA-seq). By taking advantage of sensitivity of scRNA-seq, we found that TiO 2 NPs exposure led to profound changes in gene expression and DNA damage signaling played a pivotal role in cellular responses to TiO 2 NPs exposure. Smaller TiO 2 NPs (5, 14 nm) led to a response similar to antivirus defense, and bigger TiO 2 NPs (54, 135, and 228 nm) induced proliferation and differentiation changes in transcriptional levels. Validation experiments on representative genes showed that some genes might be served as biomarkers of TiO 2 NPs exposure. Furthermore, in vitro and in vivo analyses showed remarkable over-production of reactive oxygen species (ROS) but did not affect osteogenic differentiation potential in BMSCs. The results unveiled landscape changes in transcriptomes in BMSCs induced by TiO 2 NPs, which provides new insights into toxicity assessments of nanomaterials. [ABSTRACT FROM AUTHOR]

Zanthoxylum armatum DC is a traditional medicinal plant. It is widely used in clinical treatment and disease prevention in China, India and other regions. Modern studies have reported the phytotoxicity, cytotoxicity and the animal toxicity of Zanthoxylum armatum DC, and the damage of genetic material has been observed in plants, but the detailed mechanism has not been explored. Besides, the toxicity of normal mammalian cells has not been evaluated. To evaluate the effects and underlying mechanism of genetic material damage in BRL 3A cells induced by Zanthoxylum armatum DC. Ultra-High Performance Liquid Chromatography and Orbitrap High-Resolution Mass Spectrometry was used for identification of compounds in methanol extract of Zanthoxylum armatum DC. BRL 3A cells were incubated with different concentrations of methanol extract of Zanthoxylum armatum DC (24 h). The cytotoxicity of extract was assessed with cell viability, LDH release rate, and ROS production. The damage of genetic material was assessed with OTM value of comet cells, cell cycle and the expression levels of p-ATM, p- Chk2, Cdc25A, and CDK2. Ultra-High Performance Liquid Chromatography and Orbitrap High-Resolution Mass Spectrometry investigation revealed the presence of compounds belonging to flavonoid, fatty acid and alkaloid groups. The viability of BRL 3A cells was reduced in a time-dose dependent manner treated by methanol extract of Zanthoxylum armatum DC. It increased LDH release rate and ROS production, activated the DNA double strand damage marker of γH2AX and produced comet cells. In addition, methanol extract of Zanthoxylum armatum DC caused ATM-mediated DNA damage, further phosphorylated Chk2, inhibited cell cycle related proteins, and arrested the G1/S cycle. Methanol extract of Zanthoxylum armatum DC induces DNA damage and further leads G1/S cell cycle arrest by triggering oxidative stress in the BRL 3A cells. This study provides some useful evidences for its development as an antitumor drug via activation of ATM/Chk2. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Ginkgo biloba extract (EGb 761) is widely used to treat cerebral disorders. Clinical trials have demonstrated therapeutic benefits of EGb 761 in various vascular diseases. Because the potential pathophysiological mechanisms appear similar to those involved in aneurysmal degeneration, we postulated that EGb 761 might affect the development and progression of experimental abdominal aortic aneurysm (AAA). This study was aimed to investigate whether EGb 761 influences the development of experimental AAAs, and to explore the underlying mechanisms. Material and methods: C57/BL6 mice underwent abluminal application of CaCl2 to the abdominal aorta followed by gavages with either 200mg/kg EGb 761 per day or vehicle. Six weeks after AAA induction, aortic tissue was excised for further examinations. Results: EGb 761 treatment reduced the aneurysm size compared with vehicle-treated controls. EGb 761 had no effect on hemodynamics or macrophage infiltration in the aortic wall. However, nuclear factor κB protein levels were decreased in the aortas of EGb 761 treated animals. The increased ROS production, SOD and CAT activities, and mRNA expression of p47phox nicotinamide adenine dinucleotide phosphate oxidase were attenuated by EGb 761 treatment. Moreover, administration of EGb 761 preserved the destruction of the wavy morphology of the elastin during AAA formation. Zymographic activity of matrix metalloproteinase (MMP)-9 and MMP-2 was lowered in EGb 761 treated mice. Conclusions: These results suggest that treatment with EGb 761 in mice prevented the development of CaCl2-induced AAA. The possible mechanisms include decreased oxidative damage and inflammation, preservation of aortic wall architecture, and altered MMPs activities. [Copyright &y& Elsevier]

In this study, a gas sensor based on TiO 2 /WO 3 ·H 2 O (TW) heterojunction with high sensitivity, excellent selectivity and long-term stability for ammonia (NH 3) detection was successfully prepared by hydrothermal method. Compared with WO 3 ·H 2 O and TiO 2 , TW heterojunction shows excellent selective to NH 3 and the response varies by 3 orders of magnitude to 500 ppm NH 3 at room temperature (RT, 25 ± 3 °C). The lowest response limit of TW is 0.5 ppm and the response/recovery time is 2.35 s/1.95 s. The main reason for improving the performance of TW heterojunction to NH 3 detection is that TiO 2 nanoparticles cause more oxygen free radicals on the surface of TW heterojunction, which can react with more NH 3 molecules to release more electrons. Therefore, heterojunction structure increases the electrons and reduces the width of electron depletion layer in TW gas sensor. In addition, TW heterojunction has small and uniform particle size which can provide more active sites for the reaction between NH 3 and oxygen free radicals to release more electrons. This work provides a heterojunction structure composed of TiO 2 and WO 3 ·H 2 O to effectively improve the performance of sensor for NH 3 detection at RT, which is beneficial to the development of high-performance gas sensors. [Display omitted] TiO 2 /WO 3 ·H 2 O (TW) heterostructures are prepared by hydrothermal method. TW heterojunction improves effectively the performance of NH 3 sensor based on WO 3 ·H 2 O. TiO 2 causes more oxygen free radicals on surface of TW heterojunction. TW heterojunction increases electrons to gas sensor in gas sensitive performance tests. TW gas sensor has good moisture resistance. [ABSTRACT FROM AUTHOR]

[Display omitted] • Defective MoS 2 enhanced PCA removal of Fe3+/PS system compared with pristine MoS 2. • S defects in MoS 2 facilitated the cycle of Fe3+/Fe2+ to enhance PCA degradation. • S defects in MoS 2 increased the electron density around Mo. • S defects in MoS 2 enhanced the adsorption of Fe3+. Advanced oxidation processes (AOPs) based on persulfate (PS) has attracted great attention because of its outstanding performance for decomposing chlorinated aromatic hydrocarbons in wastewater. While Fe-based materials can effectively activate PS and are environment-friendly, the low stability of Fe2+ and little activation capability of Fe3+ limit the broad applications of Fe2+ (or Fe3+) activated PS system in practical applications. In this work, taking molybdenum disulfide (MoS 2) as the co-catalyst in Fe3+/PS system, we report a strongly enhanced persulfate activation efficiency of Fe3+/PS system by engineering S defects in MoS 2. The combination of experiments and density functional theory (DFT) calculation demonstrate that S defects in MoS 2 modify the surface charge distribution, leading to the formation of an electron deficient center near S defect and increasing the electron density near Mo site. As a result, more Fe3+ in Fe3+/PS system is reduced into Fe2+ by MoS 2 with S defects, resulting in more reactive oxygen species generated. Furthermore, S defects promote the adsorption of Fe3+ on the MoS 2 surface, which further enhance the activating performance for PS through promoting to form cycle of Fe3+/Fe2+. This work provides a new strategy for improving co-catalytic properties of MoS 2 and expands the application of Fe3+/PS system for contaminants remediation. [ABSTRACT FROM AUTHOR]

Protein kinase C (PKC)-induced phosphorylation of cardiac troponin I (cTnI) depresses the acto-myosin interaction and may be important during the progression of heart failure. Although both PKCβII and PKC∊ can phosphorylate cTnI, only PKCβ expression and activity are elevated in failing human myocardium during end-stage heart failure. Furthermore, although increased cTnI phosphorylation was observed in mice with cardiac-specific PKCβ II overexpression, no differences were observed in cTnI phosphorylation status between wild type and cardiac-specific PKC∊ overexpression mice. A potentially important downstream effector of PKCs is p90 ribosomal S6 kinase (p90RSK), which plays an important role in cell growth by activating several transcription factors as well as Na+/H+ exchanger. Since both Ser23 and Ser24 of cTnI are contained in putative consensus sequences of p90RSK phosphorylation sites, we hypothesized that p90RSK is downstream from PKCβ II and can be a cTnI (Ser23/24) kinase, p90RSK, but not ERK½ activation, was increased in PKCβII overexpression mice but not in PKC∊ overexpression mice. p90RSK could phosphorylate cTnI in vitro with high substrate affinity but not cardiac troponin T (cTnT). To confirm the role of p90RSK in cTnI phosphorylation in vivo, we generated adenovirus containing a dominant negative form of p90RSK (Ad-DN-p90RSK). We found that the inhibition of p90RSK prevented H2O2-mediated cTnI (Ser23/24) phosphorylation but not ERK½ and PKCα/βII activation. Next, we generated cardiac-specific p90RSK transgenic mice and observed that cTnI (Ser23/24) phosphorylation was significantly increased. LY333,531, a specific PKCβ inhibitor, inhibited both p90RSK and cTnI (Ser23/24) phosphorylation by H2O2. Taken together, our data support a new redox-sensitive mechanism regulating cTnI phosphorylation in cardiomyocytes. [ABSTRACT FROM AUTHOR]

We report here the fabrication of BHPB loaded free-standing multilayered film via alternately depositing HA and PLL-BHPB complex and explore the underlying mechanism for its enhancing wound repair process. Of note, pre-assemble PLL with BHPB amplify PLL/HA film growth via accelerating the diffusion coefficient of PLL inside the film. [Display omitted] • LBL exponential growth is amplified by precursor assembly with charge-switchable BHPB. • BHPB neutralizes excess ROS and activates intracellular ROS scavenging mechanism. • BHPB incorporated PEM can stimulate Keap1/Nrf2/HO-1 axis to combat oxidative stress. The local oxidizing microenvironment and bacterial infection, as crucial internal and external factors that hinder the healing of diabetic wounds, are two main issues to be addressed in the design of novel wound dressing materials. As an attempt to provide optimal solution to the aforementioned problems, free-standing (FS) polyelectrolyte multilayer films (PEMs) loaded with bis[2-(4-hydroxyphenyl) benzimidazole] (BHPB) were constructed by layer-by-layer (LBL) self-assembly method. The exponential growth of LBL deposition as well as the film degradation were extensively studied, our results revealed that by pre-assembling polycation with the pH-sensitive BHPB molecule, the polycation diffusivity was largely accelerated thus greatly amplified LBL film growth, ensuring the facile detachment of the PEMs from the substrates to achieve FS films. The increase in BHPB content leaded to faster film growth and slower film degradation and more sustainable BHPB release. In terms of multifunctionality, which was ideal for the design of wound dressing material, the obtained FS films exhibited effective antimicrobial and antioxidant properties thanks to the addition of bioactive BHPB. Notably, unlike traditional antioxidant materials that only neutralize reactive oxygen species (ROS), the BHPB-loaded films stimulated the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) axis, which is a vital intercellular ROS scavenging system blocked by hyperglycemia. Moreover, the wound treated by BHPB-incorporated PEMs exhibited faster healing with increased collagen deposition, enhanced angiogenesis, and rapid re-epithelialization in rat diabetic cutaneous defect models. Overall, in the perspective of cost-effectiveness and simple fabrication, the composite BHPB incorporated FS films reported in the current study showed rather promising potential in the application of diabetic wound healing. [ABSTRACT FROM AUTHOR]

• Nickel-doped α-MnO 2 was prepared via a novel ethylene glycol reduction strategy. • Ni-MnO 2 showed excellent low-temperature performance for toluene combustion. • Synergistic effect of Mn and Ni was related to the enhanced catalytic properties. • Ni doping significantly improved the toluene adsorption on the α-MnO 2 catalyst. A series of metal-doped α-MnO 2 catalysts (M-MnO 2 , M = Ni, Cu, Co) were synthesized via a novel ethylene glycol (EG) reduction strategy for the first time, based on initial reduction of KMnO 4 with EG and subsequent heteroatom doping at room temperature, and used for catalytic toluene combustion. The obtained catalysts have been full characterized by XRD, XRF, N 2 adsorption, SEM, TEM, XPS, H 2 -TPR, O 2 -TPD, and C 7 H 8 -TPSR. It was found that the catalytic properties of α-MnO 2 can be significantly improved by nickel doping, a remarkable low-temperature performance (T 90 = 199 °C) has been achieved over Ni-MnO 2 catalyst, which is among the best reported values. Meanwhile, Ni-MnO 2 has also exhibited high catalytic stability with strong water tolerance (5 vol%) in the oxidation of toluene. Herein, the relationship between catalyst structure and catalytic activity has been elucidated. The outstanding catalytic properties can be related to the synergistic effect between Mn and doped Ni species for the adsorption and activation of toluene. Significantly, the substitutional doping of Ni2+ into octahedra MnO 6 frameworks could not only improve the redox properties, lattice oxygen mobility and the formation of more active lattice oxygen, but also promote the toluene adsorption. Additionally, a potential catalytic reaction process base on the Mars and van Krevelen mechanism was also proposed. Hence, this work paves a new way for the design and synthesis of high efficient catalysts for the elimination of volatile organic compounds. [ABSTRACT FROM AUTHOR]