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Uracil DNA glycosylase (UDG) and human alkyladenine DNA glycosylase (hAAG) are the important DNA glycosylases for initiating the repair of DNA damage, and the aberrant expression of DNA glycosylases is closely associated with various diseases, such as Parkinson's disease, several cancers, and human immunodeficiency. The simultaneous detection of UDG and hAAG is helpful for the study of early clinical diagnosis. However, the reported methods for multiple DNA glycosylase assay suffer from the application of an expensive single-molecule instrument, labor-tedious magnetic separation, and complicated design. Herein, we develop a simple fluorescence method with only three necessary DNA strands for the selective and sensitive detection of multiple DNA glycosylase activity based on the generation of 3'-OH terminal-triggered encoding of multicolor fluorescence. The method can achieve the detection limits of 5.5 × 10

To discover drugs for toxoplasmosis with less side-effects and less probability to get drug resistance is eagerly appealed for pregnant women, infant or immunocompromised patients. In this work, using TgCDPK1 as drug target, we design a method to discover new inhibitors for CDPK1 as potential drug lead for toxoplasmosis with novel scaffolds based on the combination of 2D/3D-QSAR and scaffold-hopping methods. All the binding sites of the potential inhibitors were checked by docking method, and only the ones that docked to the most conserved sites of TgCDPK1, which make them have less probability to get drug resistance, were remained. As a result, 10 potential inhibitors within two new scaffolds were discovered for TgCDPK1 with experimentally verified inhibitory activities in micromole level. The discovery of these inhibitors may contribute to the drug development for toxoplasmosis. Besides, the pipeline which is composed in this work as the combination of QSAR and scaffold-hopping is simple, easy to repeat for researchers without need of in-depth knowledge of pharmacology to get inhibitors with novel scaffolds, which will accelerate the procedure of drug discovery and contribute to the drug repurposing study.

A colorimetric assay is described for sensitive determination of Hg2+ ions based on the MoS2-Au composites as peroxidase mimetics, which are synthesized by microwave-assisted solvothermal method. The addition of Hg2+ stimulates their peroxidase-like activity, along with lower Michaelis constant toward the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) with H2O2, allowing the composites for direct determination of Hg2+. A broad linear response is obtained ranging from 20 nM to 20 μM with a detection limit (LOD) of 5 nM. The superior peroxidase-like activity is attributed to the large surface area of MoS2 nanosheets and the synergistic catalytic effect of MoS2 and Au. The Hg2+-stimulation effect implies the strong interaction between Hg2+ and MoS2-Au, where the XPS results confirm the presence of metallic Hg0, indicative of an Au-Hg amalgam. This colorimetric assay is successfully applied for the determination of Hg2+ in environmental water (tap water and Yellow River water) with excellent selectivity over interfering cations.

A new type of reduction- and pH-mediated glyco-polymeric micelles was synthesized for the antitumor drug doxorubicin (DOX) delivery in this study. The micelles were constructed by a diblock copolymer (MH-S-S-AcMH) with a disulfide linkage between hydrophilic block maltoheptaose (MH) and hydrophobic block acetalated maltoheptaose (AcMH). The experimental results showed that the amphiphilic MH-S-S-AcMH with 20 nm average size could self-assemble into micelles under physiological conditions and rapidly release the conjugated drug DOX when exposed to weakly acidic (pH = 5) and reductive (10 mM DTT) environment. Fluorescence microscopy detection indicated that drug carriers can be endocytosed effectively, making the anticancer agents flow into cells and suppress the growth of HeLa tumor cells. Compared with DOX at higher dosage and MH-S-S-AcMH micelles which are non-toxic to tumor cells, cytotoxicity assays manifested that the DOX-loaded MH-S-S-AcMH micelles exhibited better toxicity to HeLa tumor cells. According to these results, the copolymer mentioned above as practically non-toxic, highly stable, novel reduction- and pH-mediated glyco-polymeric micelles could be employed in improving drug delivery efficiency and enhancing anticancer efficacy.

One-pot Cu-catalyzed tandem aerobic oxidative cyclization for the synthesis of quinolines from 2-vinylanilines/2-aryl anilines and 2-methylquinolines via C(sp3)-H/C(sp2)-H bonds functionalization has been developed. Dioxygen as an ideal oxidant has been employed for this transformation. The substrates bearing various functional groups are performed well in this process and generate the desired products in moderate to good yields.

A simple method for the preparation of allylic triflones from allenes and triflyl chloride in the presence of (EtO)2P(O)H has been developed. The features of this reaction are catalyst-free and simple starting substrates. This method tolerates diverse functional groups and substituted allylic triflones are obtained in moderate to good yields.

Tuberculosis remains one of the deadliest infectious diseases worldwide. Only 5–15% of people infected with Mycobacterium tuberculosis develop active TB disease (ATB), while others remain latently ...

A simple method for the preparation of allylic triflones from allenes and triflyl chloride in the presence of (EtO)2P(O)H has been developed. The features of this reaction are catalyst-free and simple starting substrates. This method tolerates diverse functional groups and substituted allylic triflones are obtained in moderate to good yields.

In proteomic studies, poor detection of low abundant proteins is a major problem due to the presence of highly abundant proteins. Therefore, the specific removal or depletion of highly abundant proteins prior to analysis is necessary. In response to this problem, a series of pH-sensitive functional mesoporous silica materials composed of 2–(diethylamino)ethyl methacrylate and methacrylic acid units were designed and synthesized via atom transfer radical polymerization. These functional mesoporous silica materials were characterized and their ability for adsorption and separation of proteins was evaluated. Possessing a pH-sensitive feature, the synthesized functional materials showed selective adsorption of some proteins in aqueous or buffer solutions at certain pH values. The specific removal of a particular protein from a mixed protein solution was subsequently studied. The analytical results confirmed that all the target proteins (bovine serum albumin, ovalbumin, and lysozyme) can be removed by the proposed materials from a five–protein mixture in a single operation. Finally, the practical application of this approach was also evaluated by the selective removal of certain proteins from real biological samples. The results revealed that the maximum removal efficiencies of ovalbumin and lysozyme from egg white sample were obtained as 99% and 92%, respectively, while the maximum removal efficiency of human serum albumin from human serum sample was about 80% by the proposed method. It suggested that this treatment process reduced the complexity of real biological samples and facilitated the identification of hidden proteins in chromatograms.

A colorimetric assay is described for sensitive determination of Hg

One-pot Cu-catalyzed tandem aerobic oxidative cyclization for the synthesis of quinolines from 2-vinylanilines/2-arylanilines and 2-methylquinolines via C(sp

In the present study, ZnS and ZnO quantum dots (QDs) were synthesized via an all-aqueous process with polyethylene glycol (PEG) chains on their surface, and their toxicity as well as biodistribution were evaluated. No haemolysis occurred at a high concentration of 1600 µg/mL in vitro haemolytic assay, which demonstrated that the QDs-PEG displayed good blood compatibility. Following intravenous administration at 2, 6, and 20 mg/kg of the QDs-PEG in mice, the biodistribution, excretion and biocompatibility were characterized at 1 h, 24 h and 7 days, respectively. Quantitative analysis results indicated that the biodistribution trend of ZnS QDs-PEG was similar to that of ZnO QDs-PEG. The QDs-PEG were mainly trapped in the lung and liver, and almost removed from blood within 1 h. QDs-PEG were primarily excreted in faeces at the 2 and 6 mg/kg doses. Coefficients, haematology, blood biochemistry and histopathology results indicated that the QDs-PEG were safe and biocompatible.

We developed a novel chitosan-based luminescent/magnetic hybrid nanoparticles with folate-conjugated tetrapeptide composites (CLMNPs-tetrapeptide-FA) by conjugation in situ. First, chitosan, CdTe quantum dots (QDs), and superparamagnetic iron oxide were directly gelled into ternary hybrid nanogels. Subsequently, tetrapeptides (GFFG and LGPV) and folate were conjugated orderly into the hybrid nanoparticles. The morphology, composition, and properties of the as-prepared copolymers have also been characterized and determined using TEM, EDX, XRD, FTIR spectra, DLS, fluorescence spectroscopy, VSM, and fluorescence microscopy imaging studies. The size range of the end product CLMNPs-tetrapeptide-FA copolymers was from 150 to 190 nm under simulated physiological environment. In vivo, the experimental results of magnetic accumulation showed that the copolymers could be trapped in the tumor tissue under magnetic guidance. Under the present experimental conditions, the loading efficiencies of CPT were approximately 8.6 wt % for CLMNPs-GFFG-FA and 1.1 wt % for CLMNPs-LGPV-FA, respectively. The CPT cumulative release under dialysis condition mainly occurred for the first 28 h, and could reach 55% at pH 5.3 and 46% at pH 7.4 from CPT-loaded CLMNPs-GFFG-FA, and 69% at pH 5.3 and 57% at pH 7.4 from CPT-loaded CLMNPs-LGPV-FA within 28 h, respectively. The hemolysis percentages (

Sulfonic acid-functionalized SBA-15 mesoporous molecular sieve (SBA-15-SO 3 H and SBA-15-po-SO 3 H) were synthesized by two post-synthesis methods. The functionalized SBA-15 materials were characterized and used to investigate the adsorption behavior for proteins (bovine serum albumin and cytochrome c) and polypeptides (insulin and glucagon) in the static and dynamic processes. The adsorption conditions: including adsorption time, pH and ionic strength of sample solution were investigated in the static adsorption mode. Under optimal conditions, SBA-15-SO 3 H and SBA-15-po-SO 3 H had a maximum capacity for insulin of 430 and 451 mg/g and for glucagon of 1303 and 1094 mg/g, respectively. In addition, the two functionalized SBA-15 mesoporous materials showed selectively adsorption of proteins in the dynamic adsorption mode. Compared with SBA-15, the surface modification of SBA-15 was responsible for the selective adsorption of proteins and high adsorption capacity for some biomolecules. It indicated that the two functionalized materials could be used as adsorbents to immobilize or separate biomolecules.

The mechanism of interaction between mangiferin (MA) and bovine serum albumin (BSA) in aqueous solution was investigated by fluorescence spectra, synchronous fluorescence spectra, absorbance spectra and Fourier transform infrared (FT-IR) spectroscopy. The binding constants and binding sites of MA to BSA at different reaction times were calculated. And the distance between MA and BSA was estimated to be 5.20 nm based on Foster's theory. In addition, synchronous fluorescence and FT-IR measurements revealed that the secondary structures of the protein changed after the interaction of MA with BSA. As a conclusion, the interaction between the anti-diabetes Chinese medicine MA and BSA may provide some significant information for the mechanism of the traditional chinese medicine MA on the protein level to cure diabetes or other diseases.

Selective enrichment or removal of specific proteins prior to analysis can minimize nonspecific interferences as well as information loss, which has been an important issue in current proteomics fields. In this work, two kinds of mesoporous silica SBA-15 (mean pore diameter of 5 nm and 7 nm), bifunctionalized with quaternary ammonium and C18 groups via silylanization reaction, was used to investigate the adsorption behavior for different proteins (bovine serum albumin (BSA), ovalbumin (OVA), hemoglobin (Hb), lysozyme (Lys) and cytochrome c (cyt c)). As possessing anion exchange (quaternary ammonium) groups, the bifunctionalized SBA-15 showed selective adsorption of the negative charged proteins, BSA and OVA. Based on these properties, sequential fractionation based on different SBA-15 materials as micropipette tip sorbents was developed for sample preparation prior to protein analysis. As expected, after the sequential treatment of the sample, the detection signal of the high abundant BSA was significantly decreased and that of the low abundant cyt c was obviously enlarged, which solved the problem that low abundant protein was suppressed by adjacent high abundant protein. The sample preparation technique significantly improved protein identification and this sequential fractionation approach could be potentially applied to extend information on the protein identification for biological samples with a wide dynamic range.