A Versatile Visual Molecular Imprinting-Driven Switchable Nanozyme Activity-Based Trimodal Assay and Logic Gate Circuits of Ethyl Carbamate.

Concerns regarding the hazard of the carcinogenic ethyl carbamate (EC) have driven attempts to exploit efficient, timely, straightforward, and economic assays for warning early food safety. Here, we proposed a novel molecularly imprinted polymer Co@MOF-MIP, with a high peroxidase (POD)-like activity and a bright blue fluorescence emission, to develop a versatile visual assay for colorimetric, fluorescent, and photothermal trimodal detection and logic gate outputting of EC. Briefly, the POD-like activity of Co@MOF-MIP made it to decompose H2O2 into ·OH for oxidizing colorless 3,3',5,5'-tetramethylbenzidine (TMB) into a blue oxTMB, resulting in a 660 nm irradiated photothermal effect and bursting the blue fluorescence of Co@MOF-MIP via inner filter effect, observing a decreased fluorescence signal together with an increased colorimetric and 660 nm irradiated photothermal signals. However, EC could specifically fill the imprinted cavities of Co@MOF-MIP to block the catalytic substrates TMB and H2O2 out of Co@MOF-MIP for further reacting with the inside catalytic center of Co2+, resulting in the transformation suppressing of TMB into oxTMB, yielding an EC concentration-dependent trimodal responses in fluorescence signal enhancement, colorimetric, and 660 nm irradiated photothermal signal decreases. Assisted by the portable devices such as smartphones and hand-held thermal imagers, a visual onsite portable trimodal analytical platform was proposed for EC fast and accurate detection with the low detection limits of 1.64, 1.24, and 1.78 µg/L in colorimetric, fluorescent, and photothermal modes, respectively. Interestingly, these reactive events could be programmed by the classical Boolean logic gate analysis to offer a novel promising avenue for the big data Internet of Things monitoring and warning early residual EC in a more intelligent, dynamical, fast, and accurate manner, safeguarding food safety.

Intelligent onsite dual-modal assay based on oxidase-like fluorescence carbon dots-driven competitive effect for ethyl carbamate detection.

Intelligent onsite accurate monitoring ethyl carbamate (EC, a group 2 A carcinogen) in environment is of great significance to safeguard environmental health and public safety. Herein, we reported an intelligent dual-modal point-of-care (POC) assay based on the bimetallic Mn and Ce co-doped oxidase-like fluorescence carbon dots (Ce&MnCDs) nanozyme-driven competitive effect. In brief, the oxidase-like activity of Ce&MnCDs was inhibited by thiocholine (TCh, originating from the hydrolysis of acetylcholinesterase (AChE) to acetylthiocholine (ATCh)), preventing the oxidation of o-phenylenediamine (OPD) to 2,3-diaminophenothiazine (DAP). However, with the aid of Br2 + NaOH, EC inactivated AChE to prevent TCh generation for re-launching the oxidase-like activity of Ce&MnCDs to trigger the oxidation of OPD into DAP, thereby outputting an EC concentration-dependent ratiometric fluorescence and colorimetric readouts by employing Ce&MnCDs and OPD as the optical signal reporters. Interestingly, these dual-modal optical signals could be transduced into the gray values that was linearly proportional to the residual levels of EC on a smartphone-based portable platform, with a detection limit down to 1.66 µg/mL, qualifying the requirements of analysis of EC residues in real samples. This opened up a new avenue for onsite assessment of the risk of residues of EC, safeguarding environmental health and public safety.

AIE fluorescent nanozyme-based dual-mode biosensor for analysis of the bioactive component hypoxanthine in meat products.

The development of facile, low-cost reliable, and precise onsite assays for the bioactive component hypoxanthine (Hx) in meat products is significant for safeguarding food safety and public health. Herein, we proposed a smartphone-assissted aggregation-induced emission (AIE) fluorogen tetraphenylethene (TPE)-incorporated amorphous Fe-doped phosphotungstates (Fe-Phos@TPE) nanozyme-based ratiometric fluorescence-colorimetric dual-mode biosensor for achieving the onsite visual detection of Hx. When the Hx existed, xanthine oxidase (XOD) catalyzed Hx into H2O2 to be further catalyzed into •OH by the prominent peroxidase activity of Fe-Phos@TPE at pH = 6.5, resulting in the oxidization of nonfluorescent o-phenylenediamine (OPD, naked-eye colorless) to be yellow fluorescent emissive 2,3-diaminophenazine (DAP, naked-eye dark yellow) at 550 nm as well as the intrinsic blue fluorescence of Fe-Phos@TPE at 440 nm to be decreased via inner-filter effect (IFE) action, thereby realizing a multi-enzyme cascade catalytic reaction at near-neutral pH to overcome the traditional acidity dependence-induced time-consuming and low sensitivity troublesome.

Dual-Modal Bimetallic Nanozyme-Based Sensing Platform Combining Colorimetric and Photothermal Signal Cascade Catalytic Enhancement for Detection of Hypoxanthine to Judge Meat Freshness.

Considering the enormous demand for meat in people's daily lives, the development of efficient meat freshness assays is of great significance for safeguarding food safety. Here, a novel bimetallic nanozyme Fe@CeO2 with high peroxidase-like activity was first synthesized by embedding ferrocenecarboxylic acid (Fc) into hollow CeO2 nanospheres, which combined with xanthine oxidase (XOD) to develop a self-supplying H2O2-facilitated enzymatic cascade catalytic system of XOD + Fe@CeO2, yielding a meat freshness indicator hypoxanthine (Hx)-responsive colorimetric and photothermal dual-mode analytical platform for judging meat freshness upon the assistance of 3,3',5,5'-tetramethylbenzidine (TMB). Owing to the catalytic activity of XOD to convert Hx into H2O2, Fe@CeO2 rapidly dissociated it into •OH via a peroxidase activity-triggered Fenton-like reaction, emerging a typical enzymatic cascade catalytic reaction. As a result, the colorless TMB was oxidized to be the product of dark-blue oxTMB by •OH, with a chromogenic reaction-driven absorption enhancement at 652 nm, which endowed it with a significant photothermal effect under 660 nm laser irradiation. On this basis, an Hx concentration-dependent colorimetric and photothermal dual-mode signal cascade catalytic enhancement sensing platform was proposed by integrating with a Color Picker App-installed smartphone and a 660 nm laser-equipped handheld thermal imager, achieving the onsite quantitative, reliable, and visual detection of Hx in real meat samples for judging meat freshness with acceptable results. Notably, the colorimetric and photothermal dual-mode signal cascade catalytic enhancement improved not only the reliability but also the sensitivity of the assay, which provided new insights for efficient onsite visual monitoring of meat freshness to safeguard food safety.

Degradation of lomefloxacin by MoS2/MIL-53(Fe, Cu) catalyst in heterogeneous electro-Fenton process.

A novel heterogeneous catalyst named MoS2/MIL-53(Fe, Cu) (MMFC) was prepared by hydrothermal method and applied in a heterogeneous electro-Fenton (hetero-EF) system for lomefloxacin (LOM) degradation in this work. Under the optimal conditions of current density 3 mA/cm2, catalyst dosage 0.100 g/L, and initial pH 6, 93.5% LOM (2 mg/L) removal efficiency was achieved in the MMFC hetero-EF system within 60 min, indicating an obvious improvement compared with the MIL-53(Fe, Cu) hetero-EF system. The good catalytic activity was attributed to more effective active sites of the catalyst and the conversion of Fe(II)/Fe(III) and Cu(I)/Cu(II) promoted by Mo(IV) in MoS2, which could be inferred by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) characterizations. The reusability and stability of MMFC were explored based on five cyclic experiments, and the average degradation efficiency reached 73.9%. Furthermore, the hetero-EF system could achieve the total removal of moxifloxacin and tetracycline within 6 min and 40 min, respectively. Quenching experiments revealed that the hydroxyl radicals (·OH) were the main reactive radicals while superoxide radicals (·O2-) and singlet oxygen (1O2) played a certain part in LOM degradation. Finally, the possible mechanism of the hetero-EF process and LOM degradation pathways were proposed, including substitution, elimination, and cleavage of ring structures. Accounting for good catalytic performance, low preparation cost, and satisfactory versatility, the MMFC exhibited good potential to work as a hetero-EF catalyst for wastewater treatment.

Chlorine decay and disinfection by-products transformation under booster chlorination conditions: A pilot-scale study.

Booster chlorination was usually employed in water distribution systems with a long hydraulic retention time. The free chlorine decay and disinfection by-products (DBPs) transformation under booster chlorination conditions were investigated within a pilot-scale water distribution system (WDS). Compared with the initial chlorination in water plants, the loss of chlorine was relatively slow and could be described with first-order kinetic model. The rate of chlorine decay and the generation of DBPs in WDS were much greater than those in beaker. High flow rate and the hydraulic transients both promoted chlorine decay and DBPs formation, especially for dichloroacetonitrile (DCAN). The formation of trihalomethanes (THMs) and haloacetic acids (HAAs) was higher in the ductile iron pipe than in the steel pipe. After booster chlorination, THMs, HAAs, and DCAN all climbed up and then declined continuously, but the peak times were different during the reaction process. The results showed the generation period of DBPs followed the order: THMs (27 h) > HAAs (22 h) > DCAN (5 h). DCAN was not stable in WDS and could be decomposed for a long hydraulic retention time (HRT). The decrease of dichloroacetic acid (DCAA) and increase of trichloroacetic acid (TCAA) indicated that DCAA may turn into TCAA. Linear relationships between the free chlorine demand (FCD) and the generation of THMs that considered both buck water and the pipe wall, as well as the different hydraulic conditions, were established to predict the formation of DBPs in WDS after booster chlorination.

Experimental Investigations on Bond Behavior between FRP Bars and Advanced Sustainable Concrete.

In response to resource shortage and carbon dioxide emissions, an innovative type of sustainable concrete containing LC3, seawater, sea sand, and surface-treated recycled aggregates is proposed in this study to replace traditional concrete. To understand the bond properties between the sustainable concrete and CFRP bars, an investigation was conducted on the bond behavior between sand-coated CFRP bars and advanced sustainable concrete. Pull-out tests were carried out to reveal the failure mechanisms and performance of this bond behavior. The results showed that the slip increased monotonically along with the increase in confinement. The bond strength increased up to approximately 15 MPa, and the critical ratio of C/D was reached. The critical ratio approached 3.5 for the Portland cement groups, while the ratio was determined as approximately 4.5 when LC3 was introduced. When the proportion of LC3 reached 50%, there was a reduction in bond strength. A multisegmented modified bond-slip model was developed to describe the four-stage bond behavior. In terms of bond strength and slip, the proposed advanced concrete exhibited almost identical bond behavior to other types of concrete.

A Magnetic T7 Peptide&AS1411 Aptamer-Modified Microemulsion for Triple Glioma-Targeted Delivery of Shikonin and Docetaxel.

Glioma-targeted drug delivery is a hugely challenging task because of the multibarrier in the brain. In this study, we report a magnetic T7 peptide&AS1411 aptamer-modified microemulsion for triple glioma-targeted delivery of shikonin and docetaxel (Fe3O4@T7/AS1411/DTX&SKN-M). Such a system comprises two tumor-targeted ligands (T7 peptide and AS1411 aptamer), ultra-small superparamagnetic iron oxide nanoparticle (Fe3O4), and shikonin&docetaxel-coloaded microemulsion (SKN&DTX-M). Fe3O4@T7/AS1411/DTX&SKN-M is capable of stably circulating in the blood, accumulating around the brain under an external magnetic field, distributing inside the glioma via the affinity to nucleolin/transferrin receptor, and retarding the growth of orthotopic glioma. Fe3O4@T7/AS1411/DTX&SKN-M encapsulated Fe3O4 nanoparticles in the core to obtain the superparamagnetism, which did not influence the main surface properties. Introducing 6% (wt%) of DSPE-PEG2000-T7 and 180 nM of AS1411 collaboratively enhanced the murine glioma (G422) cellular uptake of Fe3O4@T7/AS1411/DTX&SKN-M and thereby achieved the strongest antiproliferation among all the groups. Notably, the drug distribution at the brain sites of orthotopic Luc-G422 glioma tumor-bearing nude mice treated with Fe3O4@T7/AS1411/DTX&SKN-M was overwhelming among all the treatments. Most importantly, Fe3O4@T7/AS1411/DTX&SKN-M not only significantly reduced the luminescence signal at the brain areas of orthotopic Luc-G422 glioma mice but also prolonged the overall survival period. The enhancement of anti-glioma efficacy was associated with down-regulating the population of CD133- and CD44-positive cells within the tumors. In summary, such a triple glioma-targeted delivery of shikonin and docetaxel using combinational magnetism and T7/AS1411 modification strategies provides a promising method for synergistic and precise glioma therapy.

Pep-1&borneol-Bifunctionalized Carmustine-Loaded Micelles Enhance Anti-Glioma Efficacy Through Tumor-Targeting and BBB-Penetrating.

Tumor-targeting and blood-brain barrier (BBB)-penetrating are highly desirable for the treatment of glioma. In this study, we developed Pep-1&borneol-bifunctionalized carmustine-loaded micelles (Pep-1/Bor/CMS-M) capable of targeting interleukin-13 receptor-overexpressed glioma and penetrating the brain microvascular endothelial cells-associated physiologic barriers. Pep-1/Bor/CMS-M were nearly spherical particles with a diameter of 32.6 ± 1.1 nm and zeta potential of -21.3 ± 3.1 mV. Carmustine (CMS) released from Pep-1/Bor/CMS-M in pH 7.4 was significantly faster than in acidic environments. In human glioma BT325 cellular studies, Pep-1/Bor/CMS-M remarkably increased the cytotoxicity, notably improved the internalization, and effectively induced the cell apoptosis. Likewise, in human brain microvascular endothelial cells, Pep-1/Bor/CMS-M obviously promoted the cellular uptake, rapidly decreased the transepithelial electrical resistance, and thereby enhanced the ability of penetration. In orthotopic Luc-BT325 glioma tumor-bearing nude mouse models, the stronger fluorescence signal and longer retention were observed in brain tissues compared with other controls, after single administration of DiD-labeled Pep-1/Bor/M (DiD/Pep-1/Bor/M). Importantly, Pep-1/Bor/CMS-M displayed the strongest inhibition of tumor growth, the longest survival period, and low systemic toxicity in treating orthotopic glioma tumor-bearing nude mice. Simultaneous functionalization of Pep-1 and borneol offers a novel strategy for designing CMS-based nanomedicine and precisely treating glioma.

Comparative Analysis of microRNA Expression Profiles of Exosomes Derived from Normal and Hypoxic Preconditioning Human Neural Stem Cells by Next Generation Sequencing.

Stroke recovery is associated with neural stem cell (NSC) development and neurovascular unit reconstruction. The exosome, as an important intercellular player in neurovascular communication, mediates neuro-restorative events by transferring exosomal protein and RNA cargoes. In this study, we explored the role of exosomal microRNAs (miRNAs) in human NSCs (hNSCs), and analyzed the expression profiles of miRNAs in hNSC-derived and hypoxic preconditioning hNSC-derived exosomes with the help of next generation sequencing (NGS). The results demonstrated that a certain proportion of miRNAs were differentially expressed in both exosomes. In addition, target gene prediction and Gene Ontology (GO) enrichment analysis showed that these genes were associated with differential miRNAs primarily participating in biological processes (regulation of cellular process), cellular component (intracellular membrane-bounded organelle), and molecular function (binding). Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) pathway enrichment data suggested that most of targeted genes involved in PI3K-Akt, Hippo, MAPK, mTOR, and Endocytosis etc. signaling pathways. We identified the interesting and important expressed miRNA and considered that miR-98-3p might be a special hNSC-derived exosomal-miRNA which was significantly downregulated under hypoxic preconditioning. The hNSCs-derived exosomes were capable of modulating gene expression or promoting stroke therapy. We observed that after hypoxic preconditioning, the functions of these exosomes were changed, and exosomal-miRNAs expression profile was different. In summary, our study suggested that hNSC-derived exosomal miRNAs including hypoxic preconditioning exosomal miRNAs provided a new strategy for the diagnosis and treatment of stroke patients.

Neural Stem Cells Alleviate Inflammation via Neutralization of IFN-γ Negative Effect in Ischemic Stroke Model.

Inflammatory response generated by ischemic stroke commonly affects functional or structural recovery. The aim of this study was to examine the IFN-γ caused inflammatory effects on NSCs in vitro and in vivo. We found that IFN-γ did not affect NSCs proliferation but increased the SOD2 level of inflammatory oxidative stress in NSCs culturing. High dose IFN-γ (500 ng) injection aggravated the level of inflammation in the cerebral ischemic model but did not alter the repairing functions of the NSCs in vivo. NSCs based treatment, including the NSCs-IFN-γ combined treatment, significantly improved the ischemic microenvironment by decreasing CD4+, CD8+ T cells and microglia infiltration. Furthermore, anti-inflammatory cytokines IL-10 and TGF-ß1 expression were increased in the NSCs and combined treatment groups, but the level of pro-inflammatory cytokines (IL-1 ß, IL-6, IFN-γ, and TNF-α) were decreased. The IFN-γ/Stat1 signaling pathway was also activated. NSCs transplantation therefore promoted the neurological recovery of ischemic stroke rats mainly by altering the inflammatory microenvironment, neutralizing the negative effect of IFN-γ. In conclusion, in addition to promoting cell replacement or engraftment, the NSCs-based transplantation also enhanced the therapeutic effects of transplantation by optimizing its immune microenvironment of ischemic areas.

Interferon-γ Promotes Neuronal Repair by Transplanted Neural Stem Cells in Ischemic Rats.

Ischemic stroke represents the leading cause of adult neurological disability, with no effective therapeutic strategy. Stem cell transplantation promises a new promising for treating stroke, through cell replacement and cytokine paracrine. However, due to the effect of hostile immune microenvironment, the survival and differentiation of stem cells are limited in vivo. Furthermore, the delayed inflammatory response to stroke induced secondary neurological injury. IFN-γ as pro-inflammatory cytokine has the potential to protect stem cell population during inflammatory response, as well as stimulates neurogenesis of stem cells. The purpose of this study was to investigate whether co-injection of neural stem cells and IFN-γ can improve therapeutic outcomes in ischemic stroke model. In this study, we found that IFN-γ did not interfere with the proliferation of neural stem cells (NSCs) in vitro and induced levels of subsequent neuronal differentiation significantly superior to those of other four cytokines BDNF, VEGF, TGF-ß, and IGF-1. Co-delivery of IFN-γ (concentration: 50 ng) enhanced the effectiveness of NSC transplantation therapy in ischemic rats. And combined IFN-γ treatment significantly increased neurogenesis in vivo, with more BrdU/DCX dual-positive cells found in ischemic areas. Moreover, co-treatment with IFN-γ and NSCs exerted additional neurological benefits compared with NSC transplantation alone. In conclusion, low concentration of IFN-γ can promote the functions of transplanted NSCs and facilitate their ability of neurological repair. Thus, our findings suggest that co-delivery of NSCs and IFN-γ without genetic modification may be an effective, simple, and novel approach for the treatment of ischemic stroke.

PSDAAP: Provably Secure Data Authenticated Aggregation Protocols Using Identity-Based Multi-Signature in Marine WSNs.

Data authenticated aggregation is always a significant issue for wireless sensor networks (WSNs). The marine sensors are deployed far away from the security monitoring. Secure data aggregation for marine WSNs has emerged and attracted the interest of researchers and engineers. A multi-signature enables the data aggregation through one signature to authenticate various signers on the acknowledgement of a message, which is quite fit for data authenticated aggregation marine WSNs. However, most of the previous multi-signature schemes rely on the technique of bilinear pairing involving heavy computational overhead or the management of certificates, which cannot be afforded by the marine wireless sensors. Combined with the concept of identity-based cryptography, a few pairing-free identity-based multi-signature (IBMS) schemes have been designed on the basis of the integer factorization problem. In this paper, we propose two efficient IBMS schemes that can be used to construct provably secure data authenticated aggregation protocols under the cubic residue assumption, which is equal to integer factorization. We also employ two different methods to calculate a cubic root for the cubic residue number during the signer's private key extraction. The algorithms are quite efficient compared to the previous work, especially for the algorithms of the multi-signature generation and its verification.

Effect of porous structure on the electrochemical performance of FeS2 for lithium ion batteries.

Porous and solid FeS2 particles are both synthesized via solid-state reaction method using FeC2O4· 2H2O and S powder as the raw materials. The difference of the mophology is adjusted by the calcination time. The porous FeS2 electrode exhibits significantly improved and less improved electrochemical performance comparing to the solid one during the initial 15 cycles and the later cycling process, respectively. The significantly improvement in the initial 15 cycles is due to the large surface area and 3D conducting network of the porous structure, which provides large active electrochemical interface of the active particles and electrolyte, and shortens the path length for Li+ transport. The less improvement during the later cycling process is attributed to the unstable porous structure, which collapses into nanoparticles after long cycles. On the basis of the analysis, a theoretical proposal to optimize the structure of FeS2 electrode is provided.

Expression of myeloid differentiation primary response protein 88 (Myd88) in the cerebral cortex after experimental traumatic brain injury in rats.

A growing body of evidence indicates that Toll-like receptors (TLRs) and Interleukin-1 (IL-1) family have been shown to be involved in the damaging inflammatory processes associated with stroke, infection, neoplasia, and other diseases in the central nervous system. Myeloid differentiation primary response protein 88 (Myd88) is a critical adaptor protein that transmits signals for TLRs and IL-1 family. Therefore, this study aimed to detect the expression of Myd88 protein and mRNA in a rat weight-dropping trauma model and to clarify the role of Myd88 after traumatic brain injury (TBI). A total of fifty-four Sprague Dawley (SD) rats were randomly divided into control group and TBI groups at hours 6, 12 and on day 1, day 2, day 3, and day 7. The TBI groups suffered experimental TBI by improved Feeney model. Myd88 expression is measured by Reverse Transcription PCR (RT-PCR), Western blot analysis and immunohistochemistry; and nuclear factor-kappaB (NF-κB) binding activity by electrophoretic mobility shift assay (EMSA); The levels of tumor necrosis factor-α (TNF-α) and Interleukin 1ß (IL-1ß) were measured by enzyme linked immunosorbent assay (ELISA) and the intercellular adhesion molecule-1 (ICAM-1) expression by immunohistochemistry. The expression of Myd88 in the injured brain was dramatically increased through 6 h and 7 days postinjury, and peaked on 3days. NF-κB, TNF-α, IL-1ß and ICAM-1 also ascended significantly after TBI. Our data demonstrated that Myd88 was increasingly expressed in a parallel time course to the up-regulation of NF-κB, proinflammatory cytokines and ICAM-1 and there was a highly positive relationship among them. These findings might have important implications during the administration of specific Myd88 antagonists in order to prevent or reduce inflammatory response after TBI.