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Cerebral ischemic stroke stimulates excessive reactive oxygen species, which lead to blood-brain-barrier disruption, neuron death, and aggravated cerebral infarction. Thus, it is critical to develop an antioxidant strategy for stroke treatment. Herein, we report a dietary strategy to promote stroke healing using iron oxide (Fe3O4) nanoparticles with intrinsic enzyme-like activities. We find that Fe3O4 nanozymes exhibit triple enzyme-like activities, peroxidase, catalase, and superoxide dismutase, thus potentially possessing the ability to regulate the ROS level. Importantly, intragastric administration of PEG-modified Fe3O4 nanozymes significantly reduces cerebral infarction and neuronal death in a rodent model following cerebral ischemic stroke. Ex vivo analysis shows that PEG-modified Fe3O4 nanozymes localize in the cerebral vasculature, ameliorate local redox state with decreased malondialdehyde and increased Cu/Zn SOD, and facilitate blood-brain-barrier recovery by elevating ZO-1 and Claudin-5 in the hippocampus. Altogether, our results suggest that dietary PEG-modified Fe3O4 nanozymes can facilitate blood-brain-barrier reconstruction and protect neurons following ischemic stroke.

Cholelithiasis with chronic cholecystitis is prevalent and threatens human health. Most cholecystitis caused by bacterial infection or biofilms is accompanied by gallstones in the clinic, making gallbladder removal the only effective solution. Here, we provide a strategy to eliminate gallstone biofilms and dissolve gallstones by oral administration of a supernatant derived from nanoscale iron sulfide (nFeS supernatant). First, by using gallstones obtained from the clinic, we simulated biofilm formation on gallstones and tested the antibacterial activity of a nFeS supernatant

Peroxidase-mimicking nanozymes that can generate toxic hydroxyl radicals (. OH) hold great promise as antibacterial alternatives. However, most of them display optimal performance under strongly acidic conditions (pH 3-4), and are thus not feasible for many medical uses, including burn infections with a wound pH close to neutral. Herein, we report a copper-based nanozyme (CuCo2 S4 ) that exhibits intrinsic peroxidase-like activity and can convert H2 O2 into . OH at neutral pH. In particular, bimetallic CuCo2 S4 nanoparticles (NPs) exhibited enhanced peroxidase-like activity and antibacterial capacity, superior to that of the corresponding monometallic CuS and CoS NPs. The CuCo2 S4 nanozymes possessed excellent ability to kill various bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, this CuCo2 S4 nanozymes could effectively disrupt MRSA biofilms in vitro and accelerate MRSA-infected burn healing in vivo. This work provides a new peroxidase mimic to combat bacteria in neutral pH milieu and this CuCo2 S4 nanozyme could be a promising antibacterial agent for the treatment of burn infections.

Dental caries is a global risk in terms of oral health in many schoolchildren and in a vast majority of adults. The primary factor for caries formation is the attachment of bacteria on the tooth surface to form an oral biofilm which generates acids to demineralize calcium and eventually cause tooth decay. Oral biofilm elimination is still a challenge because bacteria are embedded inside with the biofilm matrix protecting them, preventing the penetration of antibiotics or bactericides. Promising strategies for disrupting oral biofilms have been developed, including the use of natural enzymes to degrade the biofilm matrix and hydrogen peroxide to kill bacteria. Here we demonstrate a strategy that combines nanozymes with peroxidase-like activity and bacteria generating biogenic hydrogen peroxide to eliminate oral biofilms for caries treatment. By using a saliva-coated hydroxyapatite disc and sectioned human tooth to mimic the real oral environment, we analyze the influence of iron oxide nanozymes or iron sulfide nanozymes on a Streptococcus mutans biofilm in the presence of Streptococcus gordonii which can generate hydrogen peroxide. Bacterial viability assays and biofilm morphology characterization show that the combination of nanozymes and bacteria remarkably reduces the bacteria number (5 lg reduction) and biofilm matrix (85% reduction). Therefore, the combination of iron-based nanozymes and hydrogen peroxide-generating bacteria may provide a new strategy for oral biofilm elimination in dental caries treatment.

Apatite is a nearly ubiquitous accessory phase in igneous rocks that crystallizes during the entire magma evolution process and has great implications for geochronology and petrogenesis. Previous studies suggested that Nb-Ta mineralization in the giant Renli deposit was genetically related to Late Jurassic two-mica monzogranite or Early Cretaceous muscovite monzogranite. Moreover, the magmatic–hydrothermal evolution of these two stages is poorly understood. In our study, we confirm that the muscovite monzogranite, biotite monzogranite, and two-mica monzogranite are all spatially associated with Nb-Ta pegmatites. We present new apatite U-Pb ages to constrain the timing of Nb-Ta mineralization and related magmatism. The results show that apatite from the two-mica pegmatite yield a lower intercept age of 130 ± 2 Ma (2σ), and apatite grains from two two-mica pegmatite samples yield a lower intercept age of 135 ± 8 Ma (2σ) and 134 ± 3 Ma (2σ), respectively. Apatite and whole-rock geochemistry suggest the oxidation degree of the Nb-Ta mineralization increases from north (RL-6) to south (RL-16) in the giant Renli deposit. This study demonstrates that a combination of apatite composition and U-Pb ages can be used to constrain the magmatic–hydrothermal evolution of granite and pegmatite-type Nb-Ta deposits.

Oncolytic adenoviruses (Ads) have gained great attention in cancer therapy because they cause direct cytolytic infection and indirectly induce antitumor immunity. However, their efficacy is compromised by host antiviral immune response, poor tumor delivery, and the immunosuppressive tumor microenvironment (TME). Here, a natural killer (NK) cell‐mediated Ad delivery system (Ad@NK) is generated by harnessing the merits of the two components for combinational immunotherapy and virotherapy of cancer. In this biohybrid system, NK cells with a tumor‐homing tropism act as bioreactors and shelters for the loading, protection, replication, amplification, and release of Ads, thereby leading to a highly efficient systemic tumor‐targeted delivery. As feedback, Ad infection offers NK cells an enhanced antitumor immunity by activating type I interferon signaling in a STAT4‐granzyme B‐dependent manner. Moreover, it is found that the Ad@NK system can relieve immunosuppression in the TME by promoting the maturation of dendritic cells and the polarization of macrophages to M1 phenotype. Both in vitro and in vivo data indicate the excellent antitumor and antimetastatic functions of Ad@NKs by destroying tumor cells, inducing immunogenic cell death, and immunomodulating TME. This work provides a clinical basis for improved oncolytic virotherapy in combination with NK cell therapy based on the inter‐supplementary biohybrid system., A natural killer cell‐based oncolytic adenovirus delivery system is developed by harnessing the merits of the two components for combinational immunotherapy and virotherapy of triple‐negative breast cancer. The powerful therapeutic efficacy of this system against the development and metastasis of tumors demonstrates the great translational potential of this combinational strategy.

BackgroundMass effects of haematoma, neuroinflammation, oxidative stress, and neuronal apoptosis are the major causes of poor prognosis of intracerebral haemorrhage (ICH). Our previous study suggests that biocompatible iron sulphide nanoparticles possess peroxidase-like activity and can release hydrogen polysulfanes, which may inhibit brain injury. The purpose of this study was to investigate the neuroprotective efficacy of diallyl disulfide (DADS)-nFeS in mice after ICH and preliminarily illustrate the potential mechanism. MethodsAdult male C57BL/6 mice (n = 176) were injected with bacterial collagenase in the striatum. In the first part, DADS-nFeS at different doses (25, 50, or 100 mg/kg) was intragastrically administered 2 h, 26 h, and 50 h before ICH. In the second and third parts, DADS-nFeS (50 mg/kg) was administered 2 h, 26 h, and 50 h before and after the induction of ICH in the pre-treatment group and post-treatment group, respectively. H&E staining was performed to detect drug toxicity. Haematoma volume measurement, Fluoro-Jade C (F-JC) staining, Nissl staining, immunofluorescence staining, western blotting, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining, malondialdehyde (MDA) and superoxide dismutase (SOD) assays, and neurobehavioural tests were performed. ResultsAll three doses of DADS-nFeS had neuroprotective effects, and 50 mg/kg resulted in the best outcome. DADS-nFeS reduced the haematoma volume and MDA content, inhibited the activation of microglia and astrocytes, progressive neuronal degeneration, and apoptosis, increased SOD activity and neuronal survival, and improved both short-term and long-term neurological functions in perihaematomal areas after ICH. Moreover, DADS-nFeS was associated with the downregulation of Iba-1, GFAP, TNF-α, IL-1β, 4-hydroxynonenal (4-HNE), and Bax/Bcl-2 levels in perihaematomal areas after ICH. Finally, post-treatment with DADS-nFeS had a better effect than pre-treatment with DADS-nFeS. ConclusionsOur study indicated that gavage administration of DADS-nFeS decreased the haematoma volume, suppressed neuroinflammation, oxidative stress, and neuronal apoptosis, and improved short- and long-term neurological functions, which was, at least in part, realized by inhibiting the activation of microglia and astrocytes, enhancing local SOD activity, and decreasing the recruitment of reactive oxygen species. Therefore, DADS-nFeS may serve as a potential therapeutic strategy via the diet against central nervous system diseases.

Mouth ulcer is associated with inflammation and high risk of bacterial infection, which aggravates the patient’s condition. Currently, there is no effective treatment for mouth ulcer. Herein, we report that vitamin-modified iron oxide nanoparticles improve the healing of mouth ulcer through anti-inflammation and antibacterial activities. We discovered that vitamin B2 (VB2) modified iron oxide nanoparticles performed enhanced peroxidase-like, catalase-like, and superoxide dismutase (SOD)-like activities, acting as typical iron oxide nanozymes (IONzymes) with triad activities. In particular, VB2 modification significantly improved the SOD-like activity, thus providing a reactive oxygen species (ROS)-scavenging ability. Cellular antioxidant experiments showed that vitamin B2 modified IONzymes (VB2-IONzymes) protect human oral keratinocytes (HOK) and BALB/3T3 cells from hydrogen peroxide (H2O2), and these cells have high biocompatibility to eukaryotic cells. In addition, VB2-IONzymes exerted an antibacterial activity against Streptococcus mutans , Staphylococcus aureus , and Escherichia coli . Importantly, VB2-IONzymes accelerated the recovery of mouth ulcer and reduced the local secretion of inflammatory factors in mouse ulcer model via ROS scavenging and antibacterial activity. Taken together, our work demonstrates that vitamin B2 modification endows iron oxide nanoparticles with enhanced enzyme-like activities and VB2-IONzymes may be a promising reagent in the treatment of mouth ulcer because of their intrinsic anti-inflammation and antibacterial capabilities.

Cerebral ischemic stroke stimulates excessive reactive oxygen species, which lead to blood-brain-barrier disruption, neuron death, and aggravated cerebral infarction. Thus, it is critical to develop an antioxidant strategy for stroke treatment. Herein, we report a dietary strategy to promote stroke healing using iron oxide (Fe

Inspired by the particularity of tumor microenvironments, including acidity and sensibility to reactive oxygen species (ROS), advanced and smart responsive nanomaterials have recently been developed. The present study synthesized tumor-targeted and pH-sensitive supramolecular micelles that self-assembled via host-guest recognition. The micelles consumed intratumoral glucose and lactate via loading with glucose oxidase (GOD) and lactate oxidase (LOD). Intratumoral glucose and lactate were converted into hydrogen peroxide (H2O2) and were sequentially reduced to highly toxic hydroxyl radicals (•OH) via the peroxidase (POD)-like activity of the loaded C-dot nanozymes. Tumor-killing effects were observed via cascade catalytic reactions. After an intravenous injection, the nanocomposite exhibited an excellent tumor-targeted ability with good biocompatibility, which demonstrated its effective antitumor effect. The nanocomposite effectively combined starvation and catalytic therapies and exerted a synergistic anticancer effect with minimal side effects and without external addition.

Peroxidase-mimicking nanozymes that can generate toxic hydroxyl radicals (

Nanozymes have been used to dealing with microbes and remarkable advances have been made in various areas. Nanozymes with peroxidase-activity such as CeO2 nanoparticles are used for colorimetric sensing of bacteria when integrated with detection antibody, which is much more rapid and lower-cost than traditional methods. Oxidase-mimic nanozymes such as Au nanoparticles (AuNP) are able to generate reactive oxide species (ROS) for killing bacteria. Plenty of nanozymes with peroxidase-activity, such as magnetic iron oxide, grapheme quantum dots have been used for combating bacteria, biofilms as well as practical wound disinfection and healing, through catalyzing H2O2 into highly toxic hydroxyl radical that can degrade the biofilm matrix and effectively kill the bacteria. Recently, a new generation of hybrid nanozymes, such as Au nanoparticles-graphitic carbon nitride (Au/g-C3N4), graphene quantum dot–Ag nanoparticles (GQD/AgNP), has been constructed with synergistically improved catalytic efficiency for more outstanding bactericidal performance. Apart from medical applications, nanozymes also have been used in industrial area. V2O5 nanowires and CeO2−x nanorods acting like natural haloperoxidase can prevent marine biofouling through catalyzing the oxidation of bromide ions with hydrogen peroxide to hypobromous acid, which interferes with the quorum sensing system of bacteria for thwarting biofilm development. Nanozymes are stable, biocompatible and not causing drug resistance, having great potential to be the substitution of conventional biocides.

Infections caused by bacteria are a growing global challenge for public health as bacteria develop resistance, which will cause the failure of anti-infective treatment eventually. An effective alternative strategy to traditional antibacterial therapy is utilizing reactive oxygen species (ROS) to kill bacteria. Here, we report a simple route to prepare PEGylated nitrogen-doped carbon capsules (PEG-N-CCs) as an antibacterial agent. The PEG-N-CCs can translate near-infrared light (NIR) into heat and produce a high concentration of ROS triggered by NIR irradiation. Both heating and ROS are critical to destroy the outer membranes and rupture cell bodies, causing DNA fragmentation and glutathione oxidation both in Gram-negative Escherichia coli, Gram-positive Staphylococcus aureus, and their multidrug-resistant strains. Moreover, PEG-N-CCs plus NIR irradiation can efficiently scavenge the existing biofilms and prevent the formation of new biofilms, killing planktonic bacteria as well as those within the biofilm. Our studies prove that the PEG-N-CCs plus NIR irradiation can provide a simple and effective platform for combating bacteria, employing carbon nanomaterials as an antibacterial alternative for treatment of infectious diseases.

Metal-carbon hybrid materials have shown promise as potential enzyme mimetics for antibacterial therapy; however, the effects of metal states and corresponding antibacterial mechanisms are largely unknown. Here, two kinds of copper/carbon nanozymes were designed, with tuned copper states from Cu

Mouth ulcer is associated with inflammation and high risk of bacterial infection, which aggravates the patient's condition. Currently, there is no effective treatment for mouth ulcer. Herein, we report that vitamin-modified iron oxide nanoparticles improve the healing of mouth ulcer through anti-inflammation and antibacterial activities. We discovered that vitamin B

Antibacterial nanomaterials provide promising alternative strategies to combat the global challenge of bacterial infection due to deteriorating resistance. However, few have been applied for intracellular bacteria killing or in vivo therapy due to potential cytotoxicity and poor biocompatibility. Here we present a strategy to generate formula suitable for in vivo anti-infective therapy by decocting antibacterial nanomaterial. An aqueous formula containing ferrous iron and polysulfide (Fe(II)Snaq) is prepared by a decoction procedure using nano-iron sulfide (nFeS) as raw substance. Theoretical calculation indicated that replacement of a sulfur atom by an oxygen atom occurred, resulting in polysulfide release and iron dissolution. The Fe(II)Snaq decocted from nFeS induced bacterial death with ferroptosis-like hallmarks, including iron enrichment, lipid peroxidation, and glutathione (GSH) depletion. The antibacterial action of Fe(II)Snaq was dependent on ferrous iron, which could be inhibited by iron chelators, ferroptosis inhibitors, and GSH, while the polysulfide prevented ferrous iron oxidation and counteracted GSH. Furthermore, Fe(II)Snaq not only killed up to 99 % of planktonic bacteria within 5 min, but also suppressed up to 90 % of intracellular Staphylococcus aureus without triggering cytotoxicity to host cell. Administration of Fe(II)Snaq achieved equivalent therapeutic effect to vancomycin for infectious pneumonia treatment and significantly prolonged the survival period of septic mice. These results indicate that aqueous ferrous polysulfide can induce ferroptosis- like death in bacteria and may be formulated as an antibacterial alternative for anti-infection therapy.

The use of natural substance to ward off microbial infections has a long history. However, the large-scale production of natural extracts often reduces antibacterial potency, thus limiting practical applications. Here we present a strategy for converting natural organosulfur compounds into nano-iron sulfides that exhibit enhanced antibacterial activity. We show that compared to garlic-derived organosulfur compounds nano-iron sulfides exhibit an over 500-fold increase in antibacterial efficacy to kill several pathogenic and drug-resistant bacteria. Furthermore, our analysis reveals that hydrogen polysulfanes released from nano-iron sulfides possess potent bactericidal activity and the release of polysulfanes can be accelerated by the enzyme-like activity of nano-iron sulfides. Finally, we demonstrate that topical applications of nano-iron sulfides can effectively disrupt pathogenic biofilms on human teeth and accelerate infected-wound healing. Together, our approach to convert organosulfur compounds into inorganic polysulfides potentially provides an antibacterial alternative to combat bacterial infections.

In this paper, we present a novel method for detecting directed network characteristics using histogram statistics based on degree distribution associated with transfer entropy. The proposed model in this paper established in information theory looks forward to learn the low dimensional representation of sample graphs, which can be obtained by transfer entropy component analysis (TECA) model. In particular, we apply transfer entropy to measure the transfer information between different time series data. For instances, for the fMRI time series data, we can use the transfer entropy to explore the connectivity between different brain functional regions effectively, which plays a significant role in diagnosing Alzheimers disease (AD) and its prodromal stage, mild cognitive impairment (MCI). With the properties of the directed graph in hand, we commence to further encode it into advanced representation of graphs based on the histogram statistics of degree distribution and multilinear principal component analysis (MPCA) technology. It not only reduces the memory space occupied by the huge transfer entropy matrix, but also enables the features to have a stronger representational capacity in the low-dimensional feature space. We conduct a classification experiment on the proposed model for the fMRI time series data. The experimental results verify that our model can significantly improve the diagnosis accuracy for MCI subjects.

Super Resolution (SR) is a complex, ill-posed problem where the aim is to construct the mapping between the low and high resolution manifolds of image patches. Anchored neighborhood regression for SR (namely A+ [15]) has shown promising results. In this paper we present a new regression-based SR algorithm that overcomes the limitations of A+ and benefits from an innovative and simple Neighbor Reconstruction Method (NRM). This is achieved by vector operations on an anchored point and its corresponding neighborhood. NRM reconstructs new patches which are closer to the anchor point in the manifold space. Our method is robust to NRM sparsely-sampled points: increasing PSNR by 0.5 dB compared to the next best method. We comprehensively validate our technique on standardised datasets and compare favourably with the state-of-the-art methods: we obtain PSNR improvement of up to 0.21 dB compared to previously-reported work.

4G has achieved considerable success because of its high data rate. But the short battery lifetime of mobile devices hinders the development of 4G. To improve energy efficiency, much effort has been made to study the process of energy consumption in smartphones. Some hardware-based methods, using expensive instruments, are correct but unhandy. Some software-based methods are flexible, but incorrect, because they often omit the influence from communication performance. This paper proposes a smartphone energy model where typical applications (HTTP and FTP) and the wireless traffic data flow are considered. Experimental results show that the energy model accurately estimates the smartphone energy consumption in one operation of the application, whose accuracy rate is higher than 90%. This work is the first step toward the development of a new software-based method, which accurately estimates smartphone energy consumption.