"One suction and one extrusion" mode-based wash-free platform for determination of breast cancer cell-derived exosomes.

A simple and wash-free POCT platform based on microcapillary was developed, using breast cancer cell-derived exosomes as a model. This method adopted the "one suction and one extrusion" mode. The hybridized complex of epithelial cell adhesion molecule (EpCAM) aptamer and complementary DNA-horseradish peroxidase conjugate (CDNA-HRP) was pre-modified on the microcapillary's inner surface. "One suction" meant inhaling the sample into the functionalized microcapillary. The exosomes could specifically bind with the EpCAM aptamer on the microcapillary's inner wall, and then the CDNA-HRP complex was released. "One extrusion" referred to squeezing the shedding CDNA-HRP into the 3,3',5,5'-tetramethylbenzidine (TMB)/H2O2 solution, and then the enzyme-catalyzed reaction would occur to make the solution yellow using sulfuric acid as the terminator. Therefore, exosome detection could be realized. The limit of detection was 2.69 × 104 particles mL-1 and the signal value had excellent linearity in the concentration range from 2.75 × 104 to 2.75 × 108 particles⋅mL-1 exosomes. In addition, the wash-free POCT platform also displayed a favorable reproducibility (RSD = 2.9%) in exosome detection. This method could effectively differentiate breast cancer patients from healthy donors. This work provided an easy-to-operate method for detecting cancer-derived exosomes without complex cleaning steps, which is expected to be applied to breast cancer screening.

DNA Hydrogelation-Enhanced Imaging Ellipsometry for Sensing Exosomal microRNAs with a Tunable Detection Range.

Conventional imaging ellipsometry-based biosensing faces the challenges of poor sensitivity and narrow dynamic range, especially for some small molecules such as microRNA. Given that detection of various exosomal miRNAs with tunable range could provide high-precision disease information and improve the accuracy of diagnosis, a sensitive imaging ellipsometry sensor was introduced to improve sensitivity with a tunable detection range by terminus-regulated DNA hydrogelation. Tetrahedron DNA probes with complementary sequence to the target miRNA were used as biorecognition elements to form DNA hydrogelation. This DNA hydrogelation was formed by template-independent and isothermal amplification on the Au film. Due to its high dielectric constant, DNA hydrogelation structure could be used for improving the sensitivity of imaging ellipsometry significantly. Importantly, by changing the cycle of the DNA hydrogelation amplification, this strategy showed a tunable detection range from fM to nM for miRNA with a limit of detection of 0.2 fM for let-7a, 10 fM for miR-375, and 40 pM for miR-21. Furthermore, it also performed satisfactorily for the miRNA sensing in 50% human serum and 50% human plasma. This DNA hydrogelation-enhanced imaging ellipsometry could broaden the applications of conventional imaging ellipsometry in biosensing and provide a sensitive method for sensing miRNAs at different abundances.

Engineering and Application of a Myoglobin Binding Split Aptamer.

Given that a split aptamer provides a chance for the development of a sandwich assay for targets with only one aptamer, it has received extensive attention in biosensing. However, due to the lack of binding mechanisms and reliable methods, there were still a few split aptamers that bind to proteins. In this work, cardiac biomarker myoglobin (Myo) was selected as a model, a new strategy of engineering split aptamers was explored with atomic force spectroscopy (AFM), and split aptamers against target protein could be achieved by choosing the optimal binding probability between split aptamers and target. Then, the obtained split aptamers were designed for Myo detection based on dynamic light scattering (DLS). The results demonstrated that the obtained split aptamers could be used to detect targets in human serum. The strategy of engineering split aptamers has the advantages of being intuitive and reliable and could be a general strategy for obtaining split aptamers.

Investigation of the interaction between split aptamer and vascular endothelial growth factor 165 using single molecule force spectroscopy.

Understanding the binding of split aptamer/its target could become a breakthrough in the application of split aptamer. Herein, vascular endothelial growth factor (VEGF), a major biomarker of human diseases, was used as a model, and its interaction with split aptamer was explored with single molecule force spectroscopy (SMFS). SMFS demonstrated that the interaction force of split aptamer/VEGF165 was 169.44 ± 6.59 pN at the loading rate of 35.2 nN/s, and the binding probability of split aptamer/VEGF165 was dependent on the concentration of VEGF165 . On the basis of dynamic force spectroscopy results, one activation barrier in the dissociation process of split aptamer/VEGF165 complexes was revealed, which was similar to that of the intact aptamer/VEGF165 . Besides, the dissociation rate constant (koff ) of split aptamer/VEGF165 was close to that of intact aptamer/VEGF165 , and the interaction force of split aptamer/VEGF165 was higher than the force of intact aptamer/VEGF165 . It indicated that split aptamer also possessed high affinity with VEGF165 . The work can provide a new method for exploring the interaction of split aptamer/its targets at single-molecule level.

Photothermal and fluorescent dual-mode assay based on the formation of polydopamine nanoparticles for accurate determination of organophosphate pesticides.

A photothermal and fluorescent dual-mode assay for sensitive organophosphate pesticides (Ops) determination is reported based on alkaline phosphatase (ALP)-inhibition-induced formation of polydopamine (PDA) nanoparticles. In the presence of ALP, ascorbic acid 2-phosphate (AAP) can be catalyzed to produce ascorbic acid (AA). AA can reduce MnO2 nanosheets, further inhibiting the oxidation of dopamine (DA). Ops as an inhibitor for ALP activity prevents the formation of AA and the reduction of MnO2 nanosheets. Eventually, the formation of PDA nanoparticles is promoted. The inhibitory effect of Ops on ALP activity causes obvious changes of photothermal signals and fluorescence signal at 495 nm. The detection limit (LOD) of dimethoate is 0.1 µM. The method displays excellent sensing capability for the dimethoate assay in real water with good recoveries of 99.4-107.6%. Graphical abstract A photothermal and fluorescent dual-mode biosensor for sensitive Ops detection was reported based on alkaline phosphatase (ALP)-inhibition-induced formation of polydopamine (PDA) nanoparticles. The dual-mode method significantly improved the accuracy and reliability of the results.

Surface plasmon resonance assay for exosomes based on aptamer recognition and polydopamine-functionalized gold nanoparticles for signal amplification.

A novel surface plasmon resonance (SPR) strategy is introduced for the specific determination of exosomes based on aptamer recognition and polydopamine-functionalized gold nanoparticle (Au@PDA NP)-assisted signal amplification. Exosomes derived from hepatic carcinoma SMMC-7721 were selected as the model target. SMMC-7721 exosomes can be specifically captured by the aptamer ZY-sls that was complementary to the DNA tetrahedron probes (DTPs), and then the CD63 aptamer-linked Au@PDA NPs recognized SMMC-7721 exosomes for signal amplification. The DTPs were modified on a Au film for preventing Au deposition on the surface during the introduction of HAuCl4, and PDA coated on the AuNPs was used to reduce HAuCl4 in situ without any reductant assistance. It results in a further enhanced SPR signal. The assay can clearly distinguish SMMC-7721 exosomes from others (HepG2 exosomes, Bel-7404 exosomes, L02 exosomes, MCF-7 exosomes, and SW480 exosomes, respectively). SMMC-7721 exosomes are specifically determined as low as 5.6 × 105 particles mL-1. The method has successfully achieved specific determination of SMMC-7721 exosomes even in 50% of human serum without any pretreatment. Graphical abstract A novel surface plasmon resonance (SPR) strategy was introduced for the specific determination of exosomes based on aptamer recognition and polydopamine functionalized gold nanoparticles (Au@PDA NPs). The SPR signal was improved using the Au@PDA NPs assisted amplification.

Extracts of Coleus forskohlii relieves cough and asthma symptoms via modulating inflammation and the extracellular matrix.

Asthma is characterized by airway inflammatory infiltration, which leads to airway remodeling and airway hyperreactivity. Coleus forskohlii (CFK) has been used to treat asthma, however, the mechanism involved is not clear. To explore the antiasthma mechanism of extracts of Coleus forskohlii (ECFK), guinea pigs were administered with a spray of phosphoric acid histamine, and rats were sensitized with ovalbumin (OVA). Hematoxylin and eosin staining (H&E) were used to evaluate pathological changes in lung tissue. Enzyme-linked immunosorbent assay (ELISA) was used to determine cytokine levels in serum and bronchoalveolar lavage fluid (BALF). Immunohistochemistry and Western blot analysis were used to assess the expression of intercellular cell adhesion molecule-1 (ICAM-1), phosphorylation of p65 (p-p65), matrix metallopeptidase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1). After ECFK treatment, the asthma incubation period of guinea pigs was significantly prolonged. The H&E results showed that the number of eosinophils in the 12.8 g/kg ECFK group was significantly lower when compared with the control group. Moreover, ELISA results demonstrated that interleukin (IL)-4, IL-5, and IL-17 in serum and BALF were significantly decreased, and interferon-γ (IFN-γ) and IL-10 were increased after ECFK treatment. In addition, ECFK treatment resulted in downregulation of ICAM-1, p-p65, MMP-9, and TIMP-1 in lung tissue after being sensitized by OVA. In conclusion, our findings indicated that ECFK significantly alleviated OVA-induced inflammatory infiltration and airway remodeling in asthma. This study laid a theoretical foundation for the clinical use of ECFK.

Aptamer as a Tool for Investigating the Effects of Electric Field on Aß40 Monomer and Aggregates Using Single-Molecule Force Spectroscopy.

The effects of electric field (EF) on amyloid proteins have been given increasing attention in regulation of amyloid-ß (Aß) aggregation and therapeutic methods because of prevalence of Alzheimer's disease. Herein, for the first time, aptamer was used as a tool for investigating the effects of EF on Aß40 monomer and Aß40 aggregates (Aß40 oligomer and Aß40 fibril) by single-molecule force spectroscopy. Interestingly, EF had different effects on Aß40 monomer and Aß40 aggregates, which might be due to the interactions of aptamer with EF-treated Aß40 monomer and Aß40 aggregates. With application of EF to Aß40 oligomer, specific interaction and binding probability of aptamer-Aß40 oligomer slightly increased. However, the interactions of aptamer with Aß40 monomer and Aß40 fibril changed greatly when EF was respectively applied to Aß40 monomer and Aß40 fibril. Meanwhile, the interaction of aptamer with Aß40 monomer changed from nonspecific binding to specific binding. And the rupture force distribution of aptamer-Aß40 fibril changed from bimodal distribution to unimodal distribution. Hence, it was presumed that Aß40 oligomer almost maintained oligomeric structure, while Aß40 fibril and Aß40 monomer changed into Aß40 oligomer when EF was applied. Subsequently, this presumption was mainly verified by atomic force microscopy imaging and circular dichroism. This work testifies that aptamer may be a valuable tool to investigate effects of EF on Aß40 monomer and Aß40 aggregates. Moreover, the established method provides a new perspective to study aggregation of amyloid proteins.

Point-of-Care Assay of Alkaline Phosphatase Enzymatic Activity Using a Thermometer or Temperature Discoloration Sticker as Readout.

Alkaline phosphatase (ALP) is a significant biomarker in clinical diagnostics, and the abnormal level of ALP enzyme in serum is closely related to various diseases such as bone or liver cancer, bone metastases, and extrahepatic biliary obstruction. Herein a simple and portable photothermal biosensor was developed for sensitive detection of ALP enzyme based on the formation of polydopamine (PDA) nanoparticles using a thermometer or temperature discoloration sticker as readout. A MnO2 nanosheet was first prepared using a novel one-pot strategy which was operationally simple and not overly time-consuming. Then dopamine (DA) was quickly polymerized into PDA nanoparticles in the presence of the MnO2 nanosheet. When the model analyte ALP was present, the substrate 2-phospho-l-ascorbic acid trisodium salt (AAP) was catalytically hydrolyzed into l-ascorbic acid (AA), resulting in the inhibition of the formation of the PDA nanoparticles owing to the fact that the MnO2 nanosheet was reduced to Mn2+ by the generated AA. Thus, a portable biosensor based on the photothermal properties of PDA nanoparticles for ALP enzyme detection was established with a detection limit as low as 0.1 U/L (thermometer) and 1 U/L (temperature discoloration sticker). In addition, it also showed excellent sensing performance for the ALP assay in human serum. Such a simple, label-free, cost-effective, and sensitive assay could exhibit real potential application for ALP detection and early diagnosis, especially in developing countries or remote regions.

Low-Fouling Surface Plasmon Resonance Sensor for Highly Sensitive Detection of MicroRNA in a Complex Matrix Based on the DNA Tetrahedron.

Antifouling surfaces that could reduce nonspecific adsorption from a complex matrix are a great challenge in surface plasmon resonance (SPR) sensors. An antifouling surface made by the covalent attachment of DNA tetrahedron probes (DTPs) onto gold surfaces demonstrated superior antifouling property against protein and cell. DTP-modified Au (DTPs-Au) film for two single protein samples (1 mg/mL myoglobin, 48 mg/mL HSA) and five complex matrices (100% serum, 100% plasma, 9.85 × 108 red cells/mL, 5% whole blood, and cell lysate) had low or ultralow adsorption amounts (≤8.0 ng/cm2). More interestingly, DTPs-Au film could also avoid Au deposition on the surface in the process of the catalytic growth of gold nanoparticles (AuNPs). Thus, a low-fouling and sensitive SPR sensor for miRNA detection in a complex matrix was developed by integrating DTPs-Au film with the catalytic growth of AuNPs. Exploiting the amplification of catalytic growth of AuNPs, the detection limit was 0.8 fM toward target let-7a. Moreover, the SPR sensor revealed excellent selectivity and could distinguish let-7a from homologous family. More importantly, the SPR sensor could be feasible for determining miRNA in 100% human serum and cancer cell lysates, and the results of detecting miRNA from cancer cells were in excellent accord with the results obtained using qRT-PCR. This assay may have great potential as an miRNA quantification method in complex samples.

Cysteine-Rich Intestinal Protein 1 Silencing Inhibits Migration and Invasion in Human Colorectal Cancer.

BACKGROUND/AIMS: Cysteine-rich intestinal protein 1 (CRIP1), a member of the LIM/double zinc finger protein family, is abnormally expressed in several tumour types. However, few data are available on the role of CRIP1 in cancer. In the present study, we aimed to investigate the expression profile and functions of CRIP1 in colorectal cancer. METHODS: To examine the protein expression level of CRIP1, immunohistochemistry (IHC) was performed on 56 pairs of colon cancer tissue samples. Western blotting was performed to investigate CRIP1 protein expression in four colon cancer cell lines. The endogenous expression of CRIP1 was suppressed using short interfering RNAs (siRNAs). Cell proliferation assays were used to determine whether CRIP1 silencing affected cell proliferation. Flow cytometry analysis was used to detect cell apoptosis. The effects of silencing CRIP1 on cell migration and invasion was detected using the transwell and wound-healing assays. RESULTS: IHC analysis showed that protein level of CRIP1 was significantly higher in tumour tissue samples than in paired non-tumour tissue samples and that the CRIP1 level was higher in metastatic tissue samples than in non-metastatic tissue samples. In addition, protein levels of CRIP1 were higher in highly metastatic colon cancer cell lines than in colon cancer cell lines with low metastasis. Further, CRIP1 silencing had no effect on cell proliferation or apoptosis in SW620 and HT29 cells. CRIP1 silencing suppressed cell migration and invasion obviously in SW620 and HT29 cells. CONCLUSION: The present study provides new evidence that abnormal expression of CRIP1 might be related to the degree of metastasis in colorectal cancer and that CRIP1 silencing could effectively inhibit migration and invasion during colorectal cancer development. These findings might aid the development of a biomarker for colon cancer prognosis and metastasis, and thus help to treat this common type of cancer.

DNA Tetrahedron-Based Valency Controlled Signal Probes for Tunable Protein Detection.

Combined detection of multiple markers related to the same disease could improve the accuracy of disease diagnosis. However, the abundance levels of multiple markers of the same disease varied widely in real samples, making it difficult for the traditional detection method to meet the requirements of a wide detection range. Herein, three kinds of cardiac biomarkers, cardiac troponin I (cTnI), myoglobin (Myo), and C-reaction protein (CRP), which were from the pM level to the µM level in real samples, were selected as model targets. Valency-controlled signal probes based on DNA tetrahedron nanostructures (DTNs) and platinum nanoparticles (PtNPs) were constructed for tunable cardiac biomarker detection. PtNPs with high horseradish peroxidase-like activity and stability served as signal molecules, and DTNs with unique spatial structure and sequence specificity were used for precisely controlling the number of connected PtNPs. By controlling the number of PtNPs connected to DTNs, monovalent, bivalent, and trivalent signal probes were obtained and were used for the detection of cardiac markers in different concentration ranges. The limit of detection of cTnI, Myo, and CRP was 3.0 pM, 0.4 nM, and 6.7 nM, respectively. Furthermore, it performed satisfactorily for the detection of cardiac markers in 10% human serum. It was anticipated that the design of valency-controlled signal probes based on DTNs and nanozymes could be extended to the construction of other multi-target detection platforms, thus providing a basis for the development of a new precision medical detection platform.

One-step multiplex analysis of breast cancer exosomes using an electrochemical strategy assisted by gold nanoparticles.

Exosomes, as a non-invasive biomarker, perform an important role in breast cancer screening and prognosis monitoring. However, establishing a simple, sensitive, and reliable exosome analysis technique remains challenging. Herein, a one-step multiplex analysis electrochemical aptasensor based on a multi-probe recognition strategy was constructed to analyze breast cancer exosomes. HER2-positive breast cancer cell (SK-BR-3) exosomes were selected as the model targets and three aptamers including CD63, HER2 and EpCAM aptamers were used as the capture units. Methylene blue (MB) functionalized HER2 aptamer and ferrocene (Fc) functionalized EpCAM aptamer, which were modified on gold nanoparticles (Au NPs), i.e. MB-HER2-Au NPs and Fc-EpCAM-Au NPs, were used as signal units. When the mixture of target exosomes, MB-HER2-Au NPs and Fc-EpCAM-Au NPs were added on the CD63 aptamer modified gold electrode, two Au NPs modified by MB and Fc could be specifically captured on the electrode by the recognition of three aptamers with target exosomes. Then one-step multiplex analysis of exosomes was achieved by detecting two independent electrochemical signals. This strategy can not only distinguish breast cancer exosomes from other exosomes (including normal exosomes and other tumor exosomes) but also HER2-positive breast cancer exosomes and HER2-negative breast cancer exosomes. Besides, it had high sensitivity and can detect SK-BR-3 exosomes with a concentration as low as 3.4 × 103 particles mL-1. Crucially, this method can be applicable to the examination of exosomes in complicated samples, which is anticipated to afford assistance for the screening and prognosis of breast cancer.

Polymer-assisted Au@PDA nanoparticles lyophilized powder with high stability and low adsorption and its application in colorimetric biosensing.

Gold nanoparticles (Au NPs) has been widely used to develop label-free colorimetric biosensors. Since the lyophilization process of Au NPs might cause various stresses and lead to irreversible aggregation, Au NPs were usually preserved in an aqueous suspension, which was inconvenienced for transportation and storage. In addition, the potential adsorption interaction between target and Au NPs was often ignored, which may lead to false-signal for Au NPs based colorimetric strategy. Herein, polydopamine-coated gold nanoparticles (Au@PDA NPs) freeze-dried powder was prepared with the assistance of polyvinylpyrrolidone (PVP) (i.e. Au@PDA-PVP NPs) or polyethylene glycol (PEG) (i.e. Au@PDA-PEG NPs). After freeze-dried powder of Au@PDA nanoparticles was redissolved, not only their spectral properties can still be maintained, but also the Au@PDA nanoparticles have nice monodispersity. Besides, the freeze-dried powder has long-term stability and could be stored for at least nine months. Since kanamycin, an aminoglycoside antibiotic, can be absorbed on the surface of Au NPs and induce easily the false signal, it was difficult to be detected using conventional Au NPs-based colorimetric method. Thus, kanamycin was chosen as the model target, a simple, sensitive and label-free colorimetric sensor was established. Given that the adsorption between kanamycin and Au@PDA-PVP NPs was effectively avoided, the possibility of false-positive signal was also reduced. The detection limit of kanamycin was 0.22 nM (S/N = 3), which was met the requirements for the detection of kanamycin residues in milk. This work not only provided an effective and facile way to prepare the nanomaterial lyophilized powder, but also expanded the application of the Au NPs based colorimetric method.

Microcapillary-based multicolor assay for quantitative and sensitive point-of-care testing of proteins.

A microcapillary-based multicolor assay was developed for proteins quantification in serum sample with the assistance of manual centrifugal platform. The proposed assay only required the operation of "one suction and one extrusion" to realize the target detection. Myoglobin (Myo), a biomarker in the early stage of acute myocardial infarction (AMI), was chosen as the model target. The microcapillary was first modified with polydopamine (PDA), then Myo aptamer was immobilized on the PDA modified microcapillary and hybridized with glucose oxidase (Gox) functionalized DNA probe (DNA-Gox). The step "one suction" referred to the inhalation of the sample into the functionalized microcapillary. Then the target Myo in the sample could bind to the Myo aptamer on the microcapillary so that DNA-Gox complexes were released from the microcapillary into solution. Through the step "one extrusion", the DNA-Gox complexes in the solution could catalyze glucose to generate hydrogen peroxide, and then the etching of gold nanorods (AuNRs) was initiated, causing a color change from brown to yellow. According to the color change based on the etching of AuNRs, as low as 0.1 nM Myo was detected with naked eyes. Combined with the manual centrifugal platform, even the Myo in the serum samples could be detected without power supply. It was expected to build a universal and adaptable sensing platform for different targets more quickly and efficiently.

Demethylation of miR-195 suppresses prostate cancer cell proliferation, migration and invasion.

Prostate cancer (PCa) is the most prevalent cancer among men and the second leading cause of tumor-associated deaths worldwide, with increasing incidence rates over the last 10 years. Recently, miR-195 was reported to be hypermethylated at its promoter CpG island and down-regulated in hepatocellular carcinoma. However, the function of miR-195 and the underlying mechanisms in PCa remain unknown. Here, we report that a significant down-regulation of microRNA-195 (miR-195) in PCa tissues and cell lines was associated with promoter methylation status. Overexpression of miR-195 significantly suppressed cell proliferation, migration, invasion and epithelial-mesenchymal transition (increased E-cadherin and decreased N-cadherin) in PCa cells. We further demonstrated that transfection with a miR-195 inhibitor reversed the inhibitory effect of the DNA methyltransferase inhibitor 5-azacytidine on the proliferation, migration and invasion ability of PCa cells. In summary, our findings suggest that miR-195 may function as a crucial tumor suppressor in PCa.

Protective effect of bone marrow mesenchymal stem cell-derived exosomes on cardiomyoblast hypoxia-reperfusion injury through the miR-149/let-7c/Faslg axis.

Ischaemia-reperfusion injury (IRI) is closely related to cardiovascular disease (CVD), which is the leading cause of death and disability. Exosomes appear to be involved in several diseases, including CVD. However, the role of mesenchymal stem cell (MSC)-derived exosomes in IRI remains unclear. miRNA expression levels in exosomes from rat normal MSCs or hypoxia-reoxygenation (H/R) MSCs were determined by qPCR and the two significantly upregulated miRNAs were selected for further investigation. Rat cardiomyoblasts (H9c2) were transfected with either miRNA mimics or scramble controls, followed by H/R induction. The effects of miRNA overexpression and exosome administration on H/R damage were then investigated. H/R increased Faslg, suppressed ß-catenin, inhibited cell proliferation and migration, and stimulated apoptosis and reactive oxygen species (ROS) production. miR-149 or Let-7c mimics or exosomes reversed H/R-induced damage. The luciferase reporter assay proved the targeted regulation of Faslg by both miR149 and Let-7c. Inhibition of ß-catenin suppressed cell migration, proliferation, and ΔΨm but increased apoptosis and ROS. Overall, bone marrow MSC-derived exosomes protected rat cardiomyoblasts from H/R injury via the miR-149/Let-7c/Faslg axis.

The mechanisms of HSA@PDA/Fe nanocomposites with enhanced nanozyme activity and their application in intracellular H2O2 detection.

Nanozymes have drawn increasing attention with their broad applications but most nanozymes lack enzyme-like molecular structures, resulting in weak selectivity and low activity. Bioinspired molecular assembly provides an extremely promising strategy to mimic natural enzyme processes and develop function enhanced architectures. Herein, a new bioinspired molecular assembly strategy based on human serum albumin@polydopamine/Fe nanocomposites (HSA@PDA/Fe NCs) was proposed, in which Fe(iii)/Fe(ii) were anchored on HSA supported on PDA. HSA@PDA/Fe NCs with iron as the active center and HSA@PDA as the skeleton showed excellent peroxidase-like activity, which was nearly 1000 times higher than that of free Fe(iii). This may be attributed to the phenomenon that the cycle of quinones and the hydroxyl group on the nanocomposite surface greatly accelerate the conversion of Fe(iii)/Fe(ii) in acidic microenvironments. Systematic experimental studies illustrated that its activity was mainly affected by the metal active center, followed by the polymeric ligand, while the protein framework has little effect on its activity. Meanwhile, even after freeze-thaw and thermal cycle tests, it also showed excellent catalytic stability. Besides, a colorimetric assay based on HSA@PDA/Fe NCs was developed for detection of H2O2in vitro and in situ detection of H2O2 generated from live cells. This work will facilitate the developments on theoretical analysis, rational design and practical applications of nanozymes based on bioinspired molecular assemblies.

Development of DNA Aptamer as a ß-Amyloid Aggregation Inhibitor.

Developing a strategy of modulating ß-amyloid (Aß) aggregation with low cost, easy synthesis, high efficiency, and biosafety is significant and a challenge for Alzheimer's disease (AD) therapy. Herein, DNA aptamer (Aß-Apt) against Aß42 obtained by in vitro selection was developed as a potent inhibitor of Aß42 aggregation for the first time. Indeed, the Aß42 monomer fibrillation was inhibited completely by Aß-Apt. Notably, the inhibition effect of Aß-Apt on the Aß42 oligomer aggregation was more obvious than that on the Aß42 monomer aggregation. It was presumed that the distinguishing effect may be attributed to different binding behaviors of Aß-Apt with Aß42 monomer and Aß42 oligomer. Surface plasmon resonance analysis demonstrated that Aß-Apt specifically recognized Aß42 monomer and Aß42 oligomer. Furthermore, the binding affinity of Aß-Apt with Aß42 oligomer was larger than that of Aß-Apt with Aß42 monomer. This work provided a promising platform with high efficiency for manipulating Aß aggregation.

[Association between hemoglobin scavenger receptor CD163 expression and coronary atherosclerotic severity in patients with coronary heart disease].

OBJECTIVE: To investigate the association between hemoglobin scavenger receptor (CD163) expression levels on monocytic surfaces and coronary atherosclerotic severity in patients with coronary heart disease (CHD) as well as the roles of CD163 in inflammation and lipidperoxidation. METHODS: Eighty-four patients were diagnosed as CHD according to the results of coronary angiography and ACC/AHA diagnostic criteria. The patients were divided into 3 groups: acute myocardial infarction (AMI) group (n = 30), unstable angina (UA) group (n = 30), stable angina (SA) group (n = 24). Another 20 patients with normal coronary artery served as control. Expression levels of CD163 on monocytes were detected by means of flow cytometry, and the results were shown as mean fluorescence intensity (mfi). All patients underwent coronary angiography and the results were further evaluated by Jenkins score. Serum CRP and LDL-C were also measured. RESULTS: The expression levels of CD163 on monocytes in peripheral blood were significantly higher in CHD patients compared to controls (P < 0.01) in the order of AMI group [(84.4 +/- 6.9) mfi] > UA group [(64.1 +/- 5.5) mfi, P < 0.01 vs. AMI] > SA group [(46.7 +/- 6.5) mfi, P < 0.01 vs. AMI and UA] > control group [(22.0 +/- 6.1) mfi, P < 0.01 vs. AMI, UA and SA]. The expression levels of CD163 on monocytes in patients with CHD were positively correlated with Jenkins score (r = 0.9107, P < 0.01), CRP (r = 0.766, P < 0.01) and LDL-C (r = 0.749, P < 0.01). CONCLUSIONS: Expression levels of CD163 was significantly increased in patients with CHD and positively correlated with coronary heart disease severity and serum CRP and LDL-C.