Size Segregation of Gold Nanoparticles into Bilayer-like Vesicular Assembly.

Size segregation of nanoparticles with different sizes into highly ordered, unique nanostructures is important for their practical applications. Herein, we demonstrate spontaneous self-assembly of the binary mixtures of small and large gold nanoparticles (GNPs; 5/15, 5/20, or 10/20 in diameter) in the presence of a tetra(ethylene glycol)-terminated octafluoro-4,4'-biphenol ligand, namely, TeOFBL, resulting in a size-segregated assembly. The outer single layer of large GNPs forming a gold nanoparticle vesicle (GNV) encapsulated the inner vesicle-like assembly composed of small GNPs, which is referred to as bilayer-like GNV and similar to the molecular bilayer structure of a liposome. The size segregation was driven by the solvophobic feature of the TeOFBLs on the surface of GNPs. A time-course study indicated that size segregation occurred instantaneously during the mixing stage of the self-organization process. The size-segregated precursors quickly fused with each other through the inner-inner and outer-outer layer fashion to form the bilayer-like GNV. This study provides a new approach to creating biomimetic bilayer capsules with different physical properties for potential applications such as surface-enhanced Raman scattering and drug delivery.

Solvent-promoted photochemical carbonylation of benzylic C-H bonds under iron catalysis.

This paper describes the iron-catalyzed photochemical carbonylation of benzylic C-H bonds resulting in the synthesis of various aryl ketones. Using 5 W blue LED irradiation, the reactions proceed smoothly in the presence of 2 mol% of FeBr3 in MeOH at 35 °C. The catalytic system could be extended for the oxidation of silane, thioether, and phosphine into silenol, sulphoxide, and phosphoxide, respectively. A mechanistic study suggests that a hydrogen bond-stabilized iron-hydroperoxo species is the reactive intermediate. It is shown that the reaction proceeds via a four-electron-transfer pathway, and a benzylic cation seems to be the crucial reactive species. The method is applied for the synthesis of pomalyst, haloperidol, melperone, and lenperone.

An Imine-Based Porous 3D Covalent Organic Polymer as a New Sorbent for the Solid-Phase Extraction of Amphenicols from Water Sample.

In this paper, an imine-based porous 3D covalent organic polymer (COP) was synthesized via solvothermal condensation. The structure of the 3D COP was fully characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and powder X-ray diffractometry, thermogravimetric analysis, and Brunauer-Emmer-Teller (BET) nitrogen adsorption. This porous 3D COP was used as a new sorbent for the solid-phase extraction (SPE) of amphenicol drugs, including chloramphenicol (CAP), thiamphenicol (TAP), and florfenicol (FF) in aqueous solution. Factors were investigated for their effects on the SPE efficiency, including the types and volume of eluent, washing speed, pH, and salinity of water. Under the optimized conditions, this method gave a wide linear range (0.1-200 ng/mL) with a high correlation coefficient value (R2 > 0.99), low limits of detection (LODs, 0.01-0.03 ng/mL), and low limits of quantification (LOQs, 0.04-0.10 ng/mL). The recoveries ranged from 83.98% to 110.7% with RSDs ≤ 7.02%. The good enrichment performance for this porous 3D COP might contribute to the hydrophobic and π-π interactions, the size-matching effect, hydrogen bonding, and the good chemical stability of 3D COP. This 3D COP-SPE method provides a promising approach to selectively extract trace amounts of CAP, TAP, and FF in environmental water samples in ng quantities.

A Review on Gold Nanotriangles: Synthesis, Self-Assembly and Their Applications.

Gold nanoparticles (AuNPs) with interesting optical properties have attracted much attention in recent years. The synthesis and plasmonic properties of AuNPs with a controllable size and shape have been extensively investigated. Among these AuNPs, gold nanotriangles (AuNTs) exhibited unique optical and plasmonic properties due to their special triangular anisotropy. Indeed, AuNTs showed promising applications in optoelectronics, optical sensing, imaging and other fields. However, only few reviews about these applications have been reported. Herein, we comprehensively reviewed the synthesis and self-assembly of AuNTs and their applications in recent years. The preparation protocols of AuNTs are mainly categorized into chemical synthesis, biosynthesis and physical-stimulus-induced synthesis. The comparison between the advantages and disadvantages of various synthetic strategies are discussed. Furthermore, the specific surface modification of AuNTs and their self-assembly into different dimensional nano- or microstructures by various interparticle interactions are introduced. Based on the unique physical properties of AuNTs and their assemblies, the applications towards chemical biology and sensing were developed. Finally, the future development of AuNTs is prospected.

Iron/photoredox dual catalysis for acyl nitrene-based C-O bond formation towards phthalides.

This paper describes iron/photoredox dual-catalyzed acyl nitrene formation and the use of acyl nitrene in constructing various C-O bonds towards phthalides. The developed reaction starts from N-methoxyl-2-alkylbenzamides. Mechanism surveys suggest the reaction involves iron nitrene-based hydrogen atom abstraction (HAA), radical-polar crossover and O-nucleophilic SN1. Distinctively, the often-reported radical rebound in previous publications is not observed. The reaction represents the first example on acyl nitrene-based synthesis of phthalides. Moreover, it also serves as a supplement for the synthesis of marketed medicines such as 3-butylphthalides (NBP), thalidomide, Pomalyst and Otezia.

Photoredox/Iron Dual-Catalyzed Insertion of Acyl Nitrenes into C-H Bonds.

In this work, the use of N-acyloxybenzamides as efficient acyl nitrene precursors under photoredox/iron dual catalysis is reported. The resulting acyl nitrenes could be captured by various types of C-H bonds and S- or P-containing molecules. Mechanism investigations suggested that the formation of the acyl nitrene from the N-acyloxybenzamide occurs by a photoredox process, and it is believed that in this redox process oxidative N-H bond cleavage of the N-acyloxybenzamide occurs prior to reductive N-O bond cleavage of the N-acyloxybenzamide.

Mn doped Prussian blue nanoparticles for T1/T2 MR imaging, PA imaging and Fenton reaction enhanced mild temperature photothermal therapy of tumor.

BACKGROUND: Combining the multimodal imaging and synergistic treatment in one platform can enhance the therapeutic efficacy and diagnosis accuracy. RESULTS: In this contribution, innovative Mn-doped Prussian blue nanoparticles (MnPB NPs) were prepared via microemulsion method. MnPB NPs demonstrated excellent T1 and T2 weighted magnetic resonance imaging (MRI) enhancement in vitro and in vivo. The robust absorbance in the near infrared range of MnPB NPs provides high antitumor efficacy for photothermal therapy (PTT) and photoacoustics imaging property. Moreover, with the doping of Mn, MnPB NPs exhibited excellent Fenton reaction activity for chemodynamic therapy (CDT). The favorable trimodal imaging and Fenton reaction enhanced mild temperature photothermal therapy in vitro and in vivo were further confirmed that MnPB NPs have significant positive effectiveness for integration of diagnosis and treatment tumor. CONCLUSIONS: Overall, this Mn doped Prussian blue nanoplatform with multimodal imaging and chemodynamic/mild temperature photothermal co-therapy provides a reliable tool for tumor treatment.

Vesicle Formation by the Self-Assembly of Gold Nanoparticles Covered with Fluorinated Oligo(ethylene glycol)-Terminated Ligands and Its Stability in Aqueous Solution.

Water-stable gold nanoparticle vesicles (GNVs) with hollow interiors have attracted attention due to their great potential for biological applications; however, their preparation through the self-assembly approaches has been restricted due to the limited understanding of their critical mechanistic issues. In this paper, we demonstrate that a fluorinated tetra (ethylene glycol) (FTEG)-terminated tetra (ethylene glycol) (EG4), namely, FTEG-EG4, ligand can self-assemble with gold nanoparticles (5 and 10 nm) into GNVs with a hollow structure in THF due to the solvophobic feature of the ligand. Time-dependent studies showed that the GNVs with a closely packed surface derived from the incomplete and irregular GNVs, but not through the fusion of the GNV precursors. After dialysis in water, the assemblies retained vesicular structures in water, even though GNVs aggregated together, which was initiated by the hydrophobic interactions between the FTEG heads of the surface ligands on GNVs. This study provides a new insight into the design of novel small surface ligands to produce water-stable GNVs for biological applications.

Ag@S-nitrosothiol core-shell nanoparticles for chemo and photothermal synergistic tumor targeted therapy.

Along with the development of controlled delivery systems for targeted therapy, 'single-strategy' therapy often fails to achieve the desired performance in real body internal environments. In such a case, it is necessary to develop synergistic therapy strategies. Herein, for the first time, we designed and synthesized hyaluronic acid (HA) modified Ag@S-nitrosothiol core-shell nanoparticles for synergistic tumor cell targeted therapy based on photothermal therapy (PTT) and nitric oxide (NO) based chemotherapy. Triggered by near-infrared irradiation (NIR), the Ag core nanoparticle would convert the light to cytotoxic heat via a surface plasmon resonance mechanism for cancer cell apoptosis. Meanwhile, responding to NIR as well as the generated heat, the S-nitrosothiol polymeric shells would give off free NO at high concentration, inducing NO based chemotherapy. Tumor cell selective cytotoxicity assay in vitro as well as tumor bearing mouse experiments in vivo demonstrated the effective photothermal and NO based chemical synergistic tumor targeted therapy. This spatiotemporally controllable system could provide a new option and era for tumor targeted therapy in the future.

Magnetic core-shell S-nitrosothiols nanoparticles as tumor dual-targeting theranostic platform.

The external force guided targeting strategy, as well as the in vivo active targeting strategy based on "ligands-receptors" on the targeting cells and tissues have attracted much research interest. Herein, a kind of hyaluronic acid (HA) and folic acid (FA) modified magnetic S-nitrosothiols core-shell nanoparticles for nitric oxide (NO) control release as dual-tumor targeting theranostic platform were described, combining the external guidance and internal active targeting properties. Confocal microscopy assay and cells cytotoxicity experiments confirmed the active tumor cells targeting recognition, cells uptake, and NO initiated cytotoxicity of the HA-FA external functional layer modified S-nitrosothiols nanoparticles in vitro. In vivo magnetic resonance imaging (MRI) characterization, bio-distribution assay in organs and tumor, significant tumor inhibition efficacy, survival units of the mice bearing tumor, as well as the systemic toxicity assay demonstrated the efficiency of cooperative tumor targeting diagnosis and controlled NO-releasing chemotherapy. To the best of our knowledge, this is the first time of the external magnet and HA-FA actively induced synergistic effect tumor targeting systems based on NO chemotherapy in vivo, serving as a new theranostic system.

Temporary Ischemia Time Before Snap Freezing Is Important for Maintaining High-Integrity RNA in Hepatocellular Carcinoma Tissues.

Background: High-throughput transcript sequencing plays an important role in the study of hepatocellular carcinoma (HCC) occurrence and development. High-quality biospecimens, especially high-quality RNA, are the most basic prerequisites for obtaining good transcript sequencing data. Our purpose was to explore the treatment conditions of in vitro ischemic tissue samples that can be used to obtain high-integrity RNA before freezing the samples in liquid nitrogen. Materials and Methods: Postoperative tumor tissues (T) and adjacent normal tissues (AN) from 50 HCC patients were randomly selected from May 5, 2017, to June 15, 2017. Postoperative tissue specimens from each HCC patient were stratified by tissue type (T or AN), ischemia time (minutes), and ischemia temperature (°C) into 16 groups: T-4°C-15 minutes, T-4°C-30 minutes, T-4°C-60 minutes, T-4°C-120 minutes, T-24°C-15 minutes, T-24°C-30 minutes, T-24°C-60 minutes, T-24°C-120 minutes, AN-4°C-15 minutes, AN-4°C-30 minutes, AN-4°C-60 minutes, AN-4°C-120 minutes, AN-24°C-15 minutes, AN-24°C-30 minutes, AN-24°C-60 minutes, and AN-24°C-120 minutes. RNA integrity was detected by RNA integrity number (RIN) and 1% agarose gel electrophoresis. Results: At an ischemia temperature of 4°C and ischemia time of >30 minutes, the RIN of T began to decrease. RIN also gradually decreased in T at an ischemia temperature of 4°C and in both T and AN at an ischemia temperature of 24°C for ischemia times 15, 30, 60, and 120 minutes. For an ischemia time ≤15 minutes and ischemia temperature 4°C or 24°C, the RINs of T and AN were significantly different. Furthermore, at ischemia temperature 4°C and ischemia time 30 and 60 minutes or ischemia temperature 24°C and ischemia time 30 minutes, the RIN of T was higher compared with AN. However, there was no significant difference in RIN between T and AN under other treatment conditions. Conclusions: Tissue quality is adversely affected by ischemia time and ischemia temperature. Therefore, temporary ischemia time (≤15 minutes) before snap freezing is key for maintaining high-integrity RNA in HCC tissues.

Molecular imprinted S-nitrosothiols nanoparticles for nitric oxide control release as cancer target chemotherapy.

It is the goal for the development of cancer target chemotherapy with specific recognition, efficient killing the tumor cells and tissues to avoid the intolerable side effects. Molecular imprinted polymer (MIPs) nanoparticles could introduce kinds of specific bio-markers (template molecules) into the nanoparticles with the subsequent removal, leaving special holes in the structure with predictable recognition specificity with cells. Herein, we design and synthesize a kind of sialic acid (SA) over-expressed tumor target hollow double-layer imprinted polymer nanoparticles with S-nitrosothiols for nitric oxide (NO)-releasing as chemotherapy. Equilibrium/selective bindings properties and probe experimental results implies that the MIPs have an intelligently selective binding to cancer cells featuring high levels of SA glyans, providing precondition for the disulfide polymer assisted cell uptake, intracellular GSH induced decomposition and rapid NO-releasing. Cytotoxicity assay with kinds of cells demonstrates the intelligent in vitro SA over-expressed tumor cells targeting recognition, intracellular delivery and cytotoxicity. In vivo bio-distribution in tumor sites and major organs, significant suppression of tumor growth, tumor-bearing mice survival unit, and the systemic toxicity investigation experiments confirm the effective chemotherapy of the S-nitrosothiols MIPs nanoparticles for the target recognition and the controlled NO release for tumor treatment comparing to the results with S-nitrosothiols CPs as delivery system. The inevitable small amount of NO leakage from S-nitrosothiols MIPs would take part in normal physiological activities and not cause serious side effects. For the first time, this kind of nitric oxide based chemotherapy and molecular-imprinting cell recognition technique both in vitro and in vivo, might provide a solution for accurate therapy to various forms of cancer with specific markers and avoid the intolerable side effects of the traditional chemotherapy treatment.

Precise design and synthesis of an AIE fluorophore with near-infrared emission for cellular bioimaging.

Organic fluorophores emerge as important stains for bioimaging and biosensing, especially for fluorophores with aggregation-induced emission characters. However, the development of organic fluorophores with efficient AIE properties expand to far-red and/or near-infrared is still a great challenge. Herein, we precisely design and synthesize a novel D-π-A type of near-infrared AIE fluorophore (TPE-PTZ-R) by introducing phenothiazine (PTZ) to modify the typical AIE unit (tetraphenylethylene, TPE). TPE-PTZ-R displays good optical properties including a large Stokes shift and typical AIE properties. We next fabricate the uniform and stable AIE nanoparticles by loading Pluronic F127 and apply it in cellular bioimaging with high uptake efficiency, low cytotoxicity and good photostability.

Glucose functionalized carbon quantum dot containing organic radical for optical/MR dual-modality bioimaging.

The organic paramagnetic compounds nitroxides have great potential as magnetic resonance imaging (MRI) contrast agents. Herein, we report the synthesis and characterization of glucose modified carbon quantum dot containing 2,2,6,6-tetramethyl-piperidinooxy (TEMPO) for targeted bimodal MR/optical imaging of tumor cells. CQD-TEMPO-Glu shows the greatest potentials for bioimaging applications in view of low cytotoxicity, good biocompatibility, green fluorescence emission and high T1 relaxivities. The in vitro MR and optical imaging results confirm enhanced cellular internalization of CQD-TEMPO-Glu in cancer cells through GLUT mediated endocytosis. These results confirm that CQD-TEMPO-Glu is expected to be widely exploited as dual-modal contrast for cancer imaging.

Conjugated Polymer Containing Organic Radical for Optical/MR Dual-Modality Bioimaging.

Optical/MRI bimodal probes have attracted much attention due to palmary soft tissue resolution and high imaging sensitivity. In this study, poly[fluorene-co-alt-p-phenylene] containing organic radical (PFP-TEMPO+) is successfully developed for optical and MRI dual-modality bioimaging. PFP-TEMPO+ displays advanced properties such as fluorescence emission, high photostablilty, reasonable T1 relaxation effect, low cytotoxicity, and good biocompatibility. Moreover, the ability of PFP-TEMPO+ for tumor tissues imaging confirms that it could be used as an optical and MRI imaging probe for in vivo imaging. The results of the present work disclose the potential applications of PFP-TEMPO+ as an optical and MRI contrast agent.

Polymyxin B as an inhibitor of lipopolysaccharides contamination of herb crude polysaccharides in mononuclear cells.

Lipopolysaccharides (LPS) contamination in herbal crude polysaccharides is inevitable. The present study was performed to explore the effect of polymyxin B on abolishing the influence of LPS contamination in mononuclear cells. LPS was pretreated with polymyxin B sulfate (PB) at different concentrations for 1, 5 or 24 h, and then used to stimulate RAW264.7 and mouse peritoneal macrophages (MPMs). The nitric oxide (NO) and tumor necrosis factor-α (TNF-α) in cell culture supernatant, as the indications of cell response, were assayed. Bupleurum chinensis polysaccharides (BCPs) with trace amount contamination of LPS was treated with PB. 30 µg·mL-1 of PB, treating LPS (10 and 1 000 ng·mL-1 in stimulating RAW264.7 and MPMs respectively) at 37 °C for 24 h, successfully abolished the stimulating effect of LPS on the cells. When the cells were stimulated with LPS, BCPs further promoted NO production. However, pretreated with PB, BCPs showed a suppression of NO production in MPMs and no change in RAW264.7. In the in vitro experiments, LPS contamination in polysaccharide might bring a great interference in assessing the activity of drug. Pretreatment with PB (30 µg·mL-1) at 37 °C for 24 h was sufficient to abolish the effects of LPS contamination (10 and 1 000 ng·mL-1).

Polysaccharides extracted from the roots of Bupleurum chinense DC modulates macrophage functions.

The present study aimed to investigate the effects of polysaccharides extracted from Bupleurum chinense DC (BCPs) on macrophage functions. In the in vivo experiment, 1 mL of 5% sodium thioglycollate was injected into the abdomen of the mice on Day 0 and macrophages were harvested on Day 4. The macrophages were cultured in plates and treated with different concentrations of BCPs and stimulus. Effects of BCPs on macrophage functions were assessed by chemotaxis assay, phagocytosis assay and Enzyme-Linked Immunosorbent Assay (ELISA). Our results showed the enhanced chemotaxis, phagocytosis and secretion of nitric oxide (NO) and inflammatory cytokines by macrophages when treated with BCPs. However, when chemotaxis and phagocytosis were up-regulated by complement components or opsonized particles, BCPs inhibited these effects. Also, the NO production induced by lipopolysaccharides (LPS) was suppressed by BCPs mildly. Moreover, BCPs had an inhibitory effect on the [Ca2+]i elevation of macrophages. These results suggested that BCPs exerted modulatory effects on macrophage functions, which may contribute to developing novel approaches to treating inflammatory diseases.

Hollow double-layered polymer nanoparticles with S-nitrosothiols for tumor targeted therapy.

Tumor targeted hollow double-layered polymer nanoparticles (HDPNs) with S-nitrosothiols for nitric oxide (NO)-release as chemotherapy were described. Via a two-stage distillation precipitation co-polymerization, simple post-treatment and S-nitrosothiol modification, the S-nitroso HDPNs showed pH and glucose dual responsiveness. This would benefit accurate binding with the sialic acid over-expressed cancer cells, providing prerequisites for the disulfide polymer assisted cell uptake, intracellular GSH induced decomposition and rapid NO release. Confocal microscopy and cytotoxicity assay with normal versus tumor cells demonstrated in vitro recognition, intracellular delivery ability and tumor cell targeting cytotoxicity. Especially worth mentioning, the inevitable small amount of NO leakage in the transmission would take part in normal physiological activities and not cause serious side effects, providing a possible solution to avoid the intolerable side effects of traditional chemotherapy treatments for cancer.

[Design of a mechanical system for the balanceable system of ambulance].

This is the design of a mechanical systems for use in the balanceable system of ambulance, which can keep the medical service bed at the ambulance level, whatever the terrain is. A level detector will detect the level state of the bed and turn it to a signal. The central processing unit will use this signal to analyse and control the movement of the motor. By this design (which uses the rolling rail as a drive transmission and makes three supports of the bed go up and down), the bed will keep level. With the use of this design, the balanceable system of ambulance can counteract 35 degrees. The error is controlled within +/- 1 degree. And the response time is within 0.3 s. The method of registration can be effective for keeping the bed at the ambulance level, and for reducing the chance of making the patient get hurt on the way to hospital.

Anti-gastric cancer active immunity induced by FasL/B7-1 gene-modified tumor cells.

AIM: To study the activation of cytotoxic T lymphocytes (CTLs) against gastric cancer cells induced by FasL/B7-1 (FB-11) gene-modified tumor cells, and to explore whether co-expression of FasL and B7-1 in SGC-7901 tumor cells could initiate synergistic antitumor effect. METHODS: FasL and B7-1 genes were transfected into human SGC-7901 gastric cancer cells with adenovirus vectors. The positive clones were selected by G418. FasL and B7-1 genes were detected by flow cytometry and RT-PCR. Abdominal infiltrating lymphocytes and sensitized spleen cells were obtained from mice that were immunized with SGC-7901/FB-11 or wild type SGC-7901 cells intraperitoneally, and cytotoxicity of these CTLs against tumor cells was determined by MTT assay. RESULTS: Flow cytometry and RT-PCR showed that FasL and B7-1 genes were highly expressed. FasL and B7-1 transfected cancer cells had a high apoptosis index. DNA laddering suggested that FasL and B7-1 genes induced gastric cancer cell apoptosis. FasL(+)/B7-1(+)SGC-7901 cells (SGC-7901/FB-11) were inoculated subcutaneously in the dorsal skin of C57BL/6 mice and then decreased their tumorigenicity greatly (z = 2.15-46.10, P<0.01). SGC-7901/FB-11 cell-sensitized mice obtained protective immune activity against the rechallenge of wild type SGC-7901 cells (z = 2.06-44.30, P<0.05). The cytotoxicity of CTLs induced by SGC-7901/FB-11 cells against SGC-7901 was significantly higher than that of CTLs activated by wild-type SGC-7901 cells (84.1+/-2.4% vs 30.5+/-2.3%, P<0.05). CONCLUSION: FasL and B7-1 genes can effectively promote the activity of CTLs against gastric cancer cells. FasL/B7-1 molecules play an important role in CTL cytotoxicity.