Latest ArticlesThe development of novel adjuvants constitutes a new strategy for the research of tumor vaccines. Immunomodulatory molecule adjuvants are one of the novel adjuvants that can effectively stimulate the pattern recognition receptors to activate the downstream pathways of immune cells. However, there are few studies on immunomodulatory molecular adjuvants associated with C-type lectin. It has been reported that GlcC14C18 is a Mincle ligand with a relatively simple structure and strong adjuvant activity in vivo. Herein, we coupled GlcC14C18 with MUC1 glycopeptide and evaluated its immune effect. In addition, we also synthesized α-GlcC14C18-MUC1 and β-GlcC14C18-MUC1 based on the two configurations of GlcC14C18 and compared their immune effects. The results show that both of the two configurations of the vaccine have a good immune effect, but to a certain extent, the immune effect of β-GlcC14C18-MUC1 is better than that of α-GlcC14C18-MUC1.
New Delhi metallo-β-lactamase 1 (NDM-1) can hydrolyze most β-lactam antibiotics, which is the major factor for drug resistance of Gram-negative bacteria. The binding of most reversible inhibitors to NDM-1 is relatively weak due to the shallow active pocket of NDM-1. Alternatively, irreversible covalent inhibitors can prevent their dissociation from the target, leading to permanent inactivation of the protein. Herein, we report a series of irreversible covalent inhibitors of NDM-1 targeting the conserved Lys211 in the active pocket. Several methods, including mass spectrometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, fluorescent labeling, and coumarin probe were used to demonstrate that pentafluorophenyl ester formed a covalent bond with Lys211. Moreover, our target inhibitor, in combination with meropenem, achieved an antibacterial effect on drug-resistant bacteria, along with an excellent safety profile. Our new strategy in designing lysine-targeted irreversible covalent NDM-1 inhibitors provides a potential option for the clinical treatment of Gram-negative bacteria.
[1n]metacyclophanes are a class of important building blocks for supramolecular assembly of artificial capsules. Herein we present the preparation and properties of a novel polyfluorinated macrocycle meta-WreathArene, a C2-symmetrical [14]metacyclophane. Adopting a cone conformation in acetone solution, the macrocycle can form dimer capsules through hydrogen bonds induced by chloride anions. Each dimer capsule consists of two meta-WreathArene and two chloride anions, and has been unambiguously characterized both in solution and in solid state.
Selective and sensitive detection of trace microRNA is important for early diagnosis of diseases due to its expression level related to diseases. Herein, a triple signal amplification strategy is developed for trace microRNA-21 (miRNA-21) detection by combining with target-triggered cyclic strand displacement reaction (TCSDR), hybridization chain reaction (HCR) and enzyme catalytic amplification. Four DNA hairpins (H1, H2, H3, H4) are employed to form an ultralong double-strand DNA (dsDNA) structure, which is initiated by target miRNA-21. As H3 and H4 are labeled with horseradish peroxidase (HRP), numerous HRPs are loaded on the long dsDNA, producing significantly enhanced electrocatalytic signals in the hydrogen peroxide (H2O2) and 3,3′,5,5′-tetramethylbenzidine (TMB) reaction strategy. Compared with single signal amplification, the triple signal amplification strategy shows higher electrochemical response, wider dynamic range and lower detection limit for miRNA-21 detection with excellent selectivity, reproducibility and stability. Taking advantage of the triple signal amplification strategy, the proposed electrochemical biosensor can detect miRNA-21 in 10 HeLa cell lysates, suggesting that it is a promising method for fruitful assay in clinical diagnosis.
Selenium plays various biological functions in the form of selenoprotein in human body. Brain is one of the most abundant organs of selenoprotein, which plays an important role in maintaining brain redox homeostasis, signal transduction pathway regulation and neuroimmune regulation. Yet, nano-selenium have attracted much attention for their high bioavailability and low toxicity. Nano-selenium are of great application potential in field of biomedical nervous system. Recently, investigation on selenoprotein and nano-selenium has gradually become a new hotspot for the important functions of selenium in human nervous system. In this article, we wish to review recent progresses and give a perspective.
Plasmon resonance energy transfer (PRET) occurs between the plasmonic nanoparticles (NPs) and organic dyes forming donor-acceptor pairs, which has great potential in quantitative analytical chemistry because of its excellent sensitivity under dark-field microscopy (DFM). Herein, we introduce supramolecular β-cyclodextrin (β-CD) to design a host-guest recognition plasmonic nano-structure modified gold nanoparticles (GNPs), while GNPs and rhodamine molecule (RB) act as the donor and acceptor, respectively. In the presence of the target cholesterol, due to the stronger binding of cholesterol with β-CD, RB molecules are released, inducing the inhibition of PRET, as well as the increase of the scattering intensity of GNPs. The proposed strategy achieves a linear range from 0.02 µmol/L to 2.0 µmol/L for cholesterol detection, and reaches a limit of detection (LOD) of 6.7 nmol/L. This host-guest recognition strategy can easily integrate receptor-donor pair into one nanoparticle, which simplifies the construction of the PRET platform, and further provides an effective approach for PRET-based analytical applications. Afterwards, the proposed PRET strategy was successfully applied for the detection of cholesterol in serum samples with high sensitivity and specificity. The proposed method provides an effective clinically potential means for the detection of cholesterol and other disease-related biomarkers.
Prodrug self-delivery carriers with targeting that specifically responded to tumor microenvironments have good potential to improve the application dilemma of approved clinical therapeutic drugs (systemic distribution and side effects). It's noted the conversion of gemcitabine (GEM) to inactive ingredients under the action of cytidine deaminase (CDA) during metabolism in vivo limits its clinical effect. A high level of reactive oxygen species (ROS) results in a high level of oxidative stress in tumor cells, which changes the expression of CDA and optimizes the metabolism of GEM in vivo and overcome drug resistance. In this study, the ROS responsive and ROS self-supplied prodrug of artemisia (ART)-thioacetal bond (TK)-GEM was synthesized and self-vectors based on ART-TK-GEM (TK@FA NPs) was prepared by using nano precipitation. ROS responsive characteristics ensure specific release of prodrugs in tumor cells with high level of ROS thereby reducing side effects on normal cells and tissues. The endogenous ROS and newly generated ROS by ART can reduce the expression of CDA and optimizes the metabolism of GEM, and the accumulated ROS can also induce apoptosis of tumor cells, realizing synergistic anti-tumor effect of chemical drugs and traditional Chinese medicines. This paper proposes a simple method by using clinically approved drugs to improve the insufficient effect of existing chemotherapy and overcome resistance, which has potential to appropriately shorten the drug development cycle and accelerate the clinical investigation of drugs.
Ultrathin two-dimensional metal-organic framework nanosheets have emerged as a promising kind of heterogeneous catalysts. Herein, we report a new kind of 2D porphyrinic metal-organic framework nanosheets of Rh2-PCN-222, which was prepared from the self-assembly of the metalloporphyrin ligand Rh(TCPP)(DCB) (TCPP = 5,10,15,20-tetrakis(4-methoxycarbonylphenyl)porphyrin; DCB = 3,4-dichlorobenzene) and ZrCl4 in the presence of two kinds of monocarboxylic acids as the modulating reagent. The thickness of Rh2-PCN-222 nanosheets was characterized by atomic force microscopy (AFM) and determined to be 5.4-9.6 nm. It was found that the axial aryl dichlorophenyl substituent, which controlled the anisotropic growth of MOFs, was essential for the formation of nanosheets. Catalytic results showed that Rh2-PCN-222 nanosheets were efficient for CO2 transformation.
Production of value-added chemicals and fuels from biomass via electrochemical methods has been of emerging interest in light of the increasing environmental, economic, and political challenges. Paired electrolysis, with anodic oxidation and cathodic reduction reactions pairing in a single electrochemical cell, offers an effective way to produce desired products in both electrodes, thus achieving complete electron economy. In this work, an efficient 5-hydroxymethylfurfural (HMF) paired electrolysis system is developed over a self-supported ultrathin Co3O4 nanoarray electrocatalyst for simultaneous production of value-added 2, 5-dihydroxymethylfuran (DHMF) and 2, 5-furandicarboxylic acid (FDCA). The as-designed paired electrolysis cell achieves a high HMF conversion and DHMF/FDCA selectivity at both anode and cathode without external hydrogen and oxygen input. A near-quantitative yield (95.7%) of FDCA and 78.8% yield of DHMF can be achieved in the paired electrolysis system, with a total Faradaic efficiency of 127%. This work will open up new opportunities in designing efficient electrochemical devices to simultaneously produce building-block chemicals from biomass-derived molecules in both anode and cathode.
(+)/(−)-Yanhusuosines A (1) and B (2), two pairs of trace benzylisoquinoline-protoberberine atropo-enantiomeric homodimers featuring an unprecedented 6/7/6/6/6/6 hexacyclic skeleton, were isolated from the tubers of Corydalis yanhusuo. The structures of (+)/(−)-1 and (+)/(−)-2 were elucidated using spectroscopic and quantum-chemical calculation approaches. (+)/(−)-Yanhusuosines A (1) and B (2) represent a new class of alkaloid dimers biogenetically constructed by a molecule of benzylisoquinoline with a unit of protoberberine via an intermolecular [4 + 3] cycloaddition. Their plausible biosynthetic pathways are discussed, and compound 2 exerted moderate inhibitory activity of NO formation in LPS induced RAW264.7 macrophages.
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