Search

Nanozyme is a class of artificial materials that possess enzyme-like activities and can overcome limitations of natural enzymes. However, controllability of the active sites, uniformity of the particles, and dispersion in the physiological media are still challenging for nanomaterial-based nanozymes. In this work, a protein-based nanozyme has been constructed by the encapsulation of hemin into the nanocavity of a recombinant human heavy chain ferritin (Ftn), generating a monodispersed peroxidase-mimetic nanozyme (hemin@Ftn). Hemin@Ftn possesses high peroxidase catalytic activity and high tolerance to the harsh environmental conditions, such as high temperature and chemical denaturant. Remarkably, hemin@Ftn can act as a colorimetric probe for the detection of tumor cells because it can selectively catalyze reactions in tumor cells. This protein-based nanozyme bridges the gap between natural enzymes and nanomaterial-based nanozymes by the incorporation of a catalytically active prosthetic group into a highly stable Ftn.

Background Microglial activation-mediated neuroinflammation plays an important role in the progression of neurodegenerative diseases. Inflammatory activation of microglial cells is often accompanied by a metabolic switch from oxidative phosphorylation to aerobic glycolysis. However, the roles and molecular mechanisms of glycolysis in microglial activation and neuroinflammation are not yet fully understood. Methods The anti-inflammatory effects and its underlying mechanisms of glycolytic inhibition in vitro were examined in lipopolysaccharide (LPS) activated BV-2 microglial cells or primary microglial cells by enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, immunoprecipitation, flow cytometry, and nuclear factor kappa B (NF-κB) luciferase reporter assays. The anti-inflammatory and neuroprotective effects of glycolytic inhibitor, 2-deoxoy-d-glucose (2-DG) in vivo were measured in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-or LPS-induced Parkinson’s disease (PD) models by immunofluorescence staining, behavior tests, and Western blot analysis. Results We found that LPS rapidly increased glycolysis in microglial cells, and glycolysis inhibitors (2-DG and 3-bromopyruvic acid (3-BPA)), siRNA glucose transporter type 1 (Glut-1), and siRNA hexokinase (HK) 2 abolished LPS-induced microglial cell activation. Mechanistic studies demonstrated that glycolysis inhibitors significantly inhibited LPS-induced phosphorylation of mechanistic target of rapamycin (mTOR), an inhibitor of nuclear factor-kappa B kinase subunit beta (IKKβ), and NF-kappa-B inhibitor alpha (IκB-α), degradation of IκBα, nuclear translocation of p65 subunit of NF-κB, and NF-κB transcriptional activity. In addition, 2-DG significantly inhibited LPS-induced acetylation of p65/RelA on lysine 310, which is mediated by NAD-dependent protein deacetylase sirtuin-1 (SIRT1) and is critical for NF-κB activation. A coculture study revealed that 2-DG reduced the cytotoxicity of activated microglia toward MES23.5 dopaminergic neuron cells with no direct protective effect. In an LPS-induced PD model, 2-DG significantly ameliorated neuroinflammation and subsequent tyrosine hydroxylase (TH)-positive cell loss. Furthermore, 2-DG also reduced dopaminergic cell death and microglial activation in the MPTP-induced PD model. Conclusions Collectively, our results suggest that glycolysis is actively involved in microglial activation. Inhibition of glycolysis can ameliorate microglial activation-related neuroinflammatory diseases.

Two series of novel NLRP3 inflammasome inhibitors are designed, synthesized, and evaluated in an effort to develop diversified analogs based on the N-(phenylcarbamoyl)benzenesulfonamide scaffold. SAR studies reveal that the sulfonylurea linker can tolerate chemical modifications with either simply changing over the position of carbonyl and sulfonyl group or structurally flexibly inserting a cyclopropyl group, leading to identification of several more potent and diversified NLRP3 antagonists (e.g., 9) with low nanomolar inhibitory activities. Further studies indicate that these two series of compounds with low cytotoxicity exhibited weak effects on the generation of NO and TNF-a. The findings may serve as good starting points for the development of more potent NLRP3 inflammasome inhibitors as valuable pharmacological probes or potential drug candidates.

Rationally constructing single-atom enzymes (SAEs) with superior activity, robust stability, and good biocompatibility is crucial for tumor therapy but still remains a substantial challenge. In this work, we adopt biocompatible carbon dots as the carrier material to load Ru single atoms, achieving Ru SAEs with superior multiple enzyme-like activity and stability. Ru SAEs behave as oxidase, peroxidase, and glutathione oxidase mimics to synchronously catalyze the generation of reactive oxygen species (ROS) and the depletion of glutathione, thus amplifying the ROS damage and finally causing the death of cancer cells. Notably, Ru SAEs exhibit excellent peroxidase-like activity with a specific activity of 7.5 U/mg, which surpasses most of the reported SAEs and is 20 times higher than that of Ru/C. Theoretical results reveal that the electrons of the Ru 4d orbital in Ru SAEs are transferred to O atoms in H2O2 and then efficiently activate H2O2 to produce •OH. Our work may provide some inspiration for the design of SAEs for cancer therapy.

A dual-functional Pt(iv) prodrug, Pt-furoxan, can release cytotoxic cisplatin and signaling molecule NO upon cellular internalization. NO modulates the cellular response towards cisplatin, leading to a synergistic anti-proliferation effect and a promising anti-metastasis effect both in vitro and in vivo.

Circularly polarized luminescence is rising to be the cynosure of a range of display and photonic technologies, including backlights, optical spintronics, and quantum information processing. Conventional strategies to directly generate circularly polarized electroluminescence from the emissive layer (EML) of organic light-emitting diodes (OLEDs), including the attachment of chiral pendants and use of chiral additives, have been well developed. Herein, we demonstrate that OLEDs based on achiral poly(9,9-di-n-hexylfluorene-alt-benzothiadiazole) (F6BT) could be induced to directly give a preferential emission of left- or right-handed circularly polarized electroluminescence just by simple treatment with circularly polarized light. The screw sense in F6BT could be easily controlled, and exhibited a strong dependence not only on the handedness but also on the wavelength of the driving circularly polarized light. This study sheds light on a unique design to realize circularly polarized electroluminescence from achiral compounds and pave the way for the fabrication of large-area and high-quality chiral optoelectronic devices.

Pt-ATRA, a carboplatin analogue containing an all-trans retinoic acid (ATRA) derivative ligand, was synthesized via a click reaction. Upon cellular internalization, Pt-ATRA exhibits a dual function, releasing an active Pt(ii) moiety to induce cell apoptosis and ATRA to inhibit tumor metastasis.

Discotic π-conjugated supramolecular assemblies, especially with chiral supramolecular nanostructures, have been attracting growing research interest due to their significant optoelectronic properties and the possibilities of their applications in the new generation of organic semiconductors. However, the impact of supramolecular chirality on their mechanical and electrical performances remains poorly understood. Herein, a series of optically active supramolecular gels were formed from achiral triphenylene derivatives by introducing limonene as the chiral source. Owing to the well-ordered supramolecular packing, the homochiral supramolecular gels exhibited greater mechanical strength and higher conductivity, compared to heterochiral architectures. The impact of supramolecular packing in homochiral or heterochiral assemblies on their resulting mechanical and electrical performances was investigated in detail, which might be of great fundamental value for the rational design of chiral π-conjugated supramolecular nanostructures for applications in chiral optoelectronics.

Chiral discrimination of amino acid enantomers could give us a better understanding of the fundamental processes in organisms since enantiomers may have opposite biological effects. However, most of the reported chiral discrimination methods were based on different interaction between the chiral host platform and amino acid enantiomers, the chiral discrimination probes using achiral host platform have not been explored yet. Herein we reported the development of an easy, rapid and sensitive discrimination methodology of amino acid enantiomers using achiral materials, which relied on the different coordination between Cu 2+ ions and amino acid enantiomers. These coordinations could result in different pH values of samples containing the same amount of l - or d -amino acid enantiomers and Cu 2+ . By introduction of pH-responsive fluorophore 5(6)-Carboxyfluorescein (CF), above pH variation could be easily detected through fluorescence (FL) spectrometter, which could be utilized to determine the variety of amino acid enantiomers (including basic and acidic amino acids). Moreover, a more convenient achiral polyacrylamide (PAM) hydrogel containing CF and Cu 2+ has also been successfully fabricated to discriminate amino acid enantiomers and even the enantiomeric excess (ee) of mixtures at the designed concentration ranges.

Microglia-mediated neuroinflammation plays an important role in the progression of neurodegenerative diseases including Parkinson's disease (PD). Pleckstrin homology-like domain family A member 1 (PHLDA1) plays an important role in immunological regulation, particularly in the Toll-like receptor-mediated immune response. Here, we explored the potential roles of PHLDA1 in microglia-mediated inflammation and neuronal protection. We found that PHLDA1 expression was rapidly increased in response to inflammatory stimuli in microglia cells in vivo or in vitro. Knockdown of PHLDA1 using adeno-associated virus serotype (AAV) ameliorated MPTP-induced motor deficits and inhibited neuroinflammation in mice. In support of this observation in vivo, we found that LPS-induced proinflammatory gene expression, including TNF-α, IL-1β, iNOS, and COX-2, was decreased in PHLDA1-deficient microglial cells. Mechanistic studies demonstrated that increased expression of PHLDA1, upon LPS stimulation in microglia, led to direct interaction with TRAF6 and enhanced its K63-linked ubiquitination-mediated NF-κB signaling activation. PHLDA1 deficiency interfered with TRAF6 K63-linked ubiquitination and inhibited microglial inflammatory responses. These findings reveal the first evidence that PHLDA1 is an important modulator of microglial function that is associated with microglia-mediated dopaminergic neurotoxicity. The data therefore provided the first evidence that PHLDA1 may be a potent modulator for neuroinflammation, and PHLDA1 may be a novel drug target for treatment of neuroinflammation-related diseases such as PD.

Dual-wavelength operation of grating-tuned dye laser systems was demonstrated in this paper. We used the second harmonic generation of a Q-switched Nd:YAG laser to pump the Nile red solvent (dissolved in ethanol) in the Littrow configuration and the Littman–Metcalf configuration. By rotating the grating 3.6° in the Littrow configuration and the tuning mirror 3.9° in the Littman–Metcalf configuration, we obtained a 72 and 46 nm tuning-range dye laser output, respectively. Meanwhile by parallelly moving the grating in the Littrow configuration and the tuning mirror in the Littman–Metcalf configuration, we achieved the separation of dual wavelength from 0.7 to 5 nm in the former and 1.5 to 4 nm in the latter, which were in the terahertz range and could find applications in the terahertz source after using difference frequency technology. Finally, after considering the laser trajectories in the two configurations, we theoretically analyzed the reasons for overall tuning and separation tuning of dual wavelength.

Chemoselective hydrogenation of aldehydes with heterogeneous catalysts under mild conditions is of great importance but remains a major challenge. Herein, an efficient strategy was developed for low temperature chemoselective hydrogenation of aldehydes with broad substrate scope over a magnetic material supported palladium catalyst (γ-Fe2O3@HAP-Pd). Aldehydes bearing various reducible functional groups readily underwent hydrogenation to give the corresponding primary alcohols with moderate to excellent yield at room temperature in aqueous solutions. The Hammett equation revealed that the hydrogenation of aromatic aldehydes proceeded via an anionic intermediate. Additionally, when the temperature increased to 70 °C, toluene was obtained by the deoxygenation of benzaldehyde in excellent yield. Furthermore, the γ-Fe2O3@HAP-Pd could be recycled up to six times without loss of activity and metal leaching.

A chitosan/hydroxyapatite nanocomposite coating was fabricated on the surface of wood from Chinese Glossy Privet (CGP) and could adhere compactly to the wood surface. Fourier transform infrared spectra analysis indicated that the interaction between chitosan and hydroxyapatite might exist. In addition, sodium bicarbonate was added into the nanocomposite during the preparation process making the boating porous in acidic surrounding through effervescence effect. Field emission scanning electron microscope characterizations showed the nanocomposite (M(CS):M(HA) = 1:1, with 30% NaHCO3) was optimal and such composite was stable, which was verified by thermal analysis and in vitro degradation study. This work could provide a facile and effective fabricating approach of biocompatible material which may have some potential applications as bone-repairing material.

An effective and convenient method using ion beam bombardment (IBB) for separating a multi-layered compact graphene oxide (GO) piece into several small few-layered loose pieces was developed, and it was found that those small GO pieces had formed a flower-like structure. Therein, the main mechanism was proposed to be the etching and charge effects of IBB. This work could provide a facile and promising approach for improving the dispersion and the related properties of GO. Furthermore, X-ray diffraction and Raman spectrum determinations demonstrated that, with the increasing fluence, IBB could effectively decrease the chemical groups in the layers of GO, resulting in the decrease of the layer distance.

Novel photocurable ternary polymer networks were prepared by incorporating N-(4-hydroxy-3-methoxybenzyl)-acrylamide (HMBA) into a cross-linked thiol–ene network based on poly(ethylene glycol)diacrylate (PEGDA) and (mercaptopropyl)methylsiloxane homopolymers (MSHP). The ternary network materials displayed bactericidal activity against Escherichia coli and Staphylococcus aureus and reduced the attachment of marine organism Phaeodactylum tricornutum. Extensive soaking of the polymer networks in aqueous solution indicated that no active antibacterial component leached out of the materials, and thus the ternary thiol–ene coating killed the bacteria by surface contact. The surface structures of the polymer networks with varied content ratios were studied by sum frequency generation (SFG) vibrational spectroscopy. The results demonstrated that the PDMS Si-CH3 groups and mimic-capsaicine groups are predominantly present at the polymer–air interface of the coatings. Surface reorganization was apparent after polyme...

A range-extended acidity detector based on Nile red was designed and analyzed in this work. In light of the good lasing property and solvatochromism characteristic of Nile red/ethanol solution, we have obtained laser spectra of sulfuric acid in different concentrations doped in this substrate. Moreover, to expand the acidity detection range, we proposed a tandem cuvette system containing rhodamine 6G/ethanol and Nile red/ethanol. Consequently, the detection range could be enlarged from 26 nm to 40 nm, by changing not only the wavelength peak but also by the intensity ratio of dual-wavelength laser output. In addition, by changing the detection and substrate materials, the whole detection range could be expanded, and therefore a wide range of applications in polarity and acidity detection could be implemented via this method.

We have reported a broadly tunable and dual-wavelength polarity amplified Nile red laser system. Combined with the method of traditional grating tuning, the broadband wavelength tuning could be realized by changing the polarity of the solvents in which Nile red dissolved, which would extend the family of organic dyes used as laser gain medium and play an important role in laser display technology as laser source. Then the dual-wavelength emission was obtained by pumping two distinct different dye solutions in series. The realization of the dual-wavelength lasing would open up an avenue to detection amplification technology, which also provided an alternative way to analyze trace amount of substances.

Wood-hydroxyapatite composite material was developed by depositing hydrated calcium hydrogen phosphate (HCHP) on the surface of wood from Chinese Glossy Privet (CGP) with polyethylene glycol (PEG, HO(CH2CH2O)nH) as the grafting agent and subsequent hydrothermal vapor treatment. The results illustrated that HCHP could adhere quickly and strongly on the PEG-grafted wood surface. Moreover, this HCHP could be efficiently transformed to hydroxyapatite (HA, Ca10(PO4)6(OH)2) by hydrothermal vapor treatment. IR, XRD analysis and SEM observation indicated that the fabricated hydroxyapatite was pure and its morphology was uniform and microporous. This work provides a new fabricating approach of biocompatible material which may have some potential applications as bone-repairing material.

Dehydrogenative cross-coupling of aldehydes with alcohols as well as dehydrogentive cross-coupling of primary alcohols to produce esters have been developed using a Rh-terpyridine catalyst. The catalyst demonstrates broad substrate scope and good functional group tolerance, affording esters highly selectively. The high chemoselectivity of the catalyst stems from its preference for dehydrogenation of benzylic alcohols over aliphatic ones. Preliminary mechanistic studies suggest that the active catalyst is a dimeric Rh(II) species, operating via a mechanism involving metal–base–metal cooperativity.

A β-cyclodextrin–graphene (β-CD–G) hybrid composite modified glassy carbon electrode for the first time was used for electrochemically detecting di(2-ethylhexyl)phthalate (DEHP), based on the inclusion of DEHP into β-CD. The electrode was characterized by cyclic voltammetry and electrochemical impedance spectroscopy. At the composites electrode, the impedance value increased linearly with the increasing DEHP concentration in the range of 2 μM to 18 μM, the limit of detection was 0.12 μM (3σ method), with a correlation coefficient of 0.998. The electrode showed good selectivity, reproducibility and stability. Obviously, the collected amounts of DEHP by β-CD–G could be detected through this electrochemical method. Furthermore, this simple and low-cost sensing platform can in principle be extended to the detection of other phthalate esters which can form host–guest complexes with cyclodextrin.