Two-Dimensional Analysis Method for Highly Sensitive Detection of Dual MicroRNAs in Breast Cancer Cells.

Multiple biomarker detection is crucial for early clinical diagnosis, and it is significant to achieve the simultaneous detection of multiple biomarkers with the same nanomaterial. In this work, the hairpin DNA strands were selectively modified on the surface of gold nanorods (AuNRs) to construct two kinds of nanoprobes by rational design. When in the presence of dual microRNAs, AuNRs were assembled to form end-to-end (ETE) and side-by-side (SBS) dimers. Compared with a single AuNR, the dark-field scattering intensity and red color percentage variation of dimers were extremely distinguished, which could be developed for dual microRNA detection by combining the red color percentage and scattering intensity with the data processing method of principal component analysis to construct a two-dimensional analysis method. Especially, the fraction of AuNR dimers presented a linear relationship with the amount of microRNAs. Based on this, microRNA-21 and microRNA Let-7a in breast cancer cells were detected with the detection limits of 1.72 and 0.53 fM, respectively. This method not only achieved the sensitive detection of dual microRNAs in human serum but also realized the high-resolution intracellular imaging, which developed a new way for the oriented assembly of nanomaterials and biological detection in living cells.

The Accurate Imaging of Collective Gold Nanorods with a Polarization-Dependent Dark-Field Light Scattering Microscope.

Anisotropic nanomaterials, such as gold nanorods (AuNRs), could be employed as an orientation platform due to their polarization-dependent surface plasmon resonance. However, a variety of factors would affect the dark-field light scattering imaging of anisotropic nanomaterials, resulting in an unstable signal, which is not advantageous to its further application. In this work, the localized surface plasmon resonance properties of a few AuNRs at different angles were excited by polarization with a conventional dark-field microscope, in which it was found that the ratio of AuNRs' light scattering intensity at different polarization angles (I) to that without a polarizer (I0) reflected the orientation information of AuNRs. Furthermore, the light scattering signal ratio between the parallel polarization (Ip) and that without a polarizer (I0) was closely related with the aspect ratio of AuNRs, which could not be affected by external conditions. To verify this concept, a highly sensitive and selective assay of the alkaline phosphatase activity in human serum was successfully developed based on the chemical etching of AuNRs, resulting in a lower aspect ratio and a lesser Ip/I0. This result holds great promise for polarization-dependent colorimetric nanomaterials and single-particle tracers in living cells.

"Hepatitis virus indicator"----the simultaneous detection of hepatitis B and hepatitis C viruses based on the automatic particle enumeration.

As the common hepatitis viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV) are important causes of liver diseases, which greatly threaten human health and public hygiene. Furthermore, due to the similar transmission routes of HBV and HCV, it is highly susceptible to suffer from the cross-infection of HBV and HCV when humans are infected by hepatitis viruses. So it is urgent to develop strategies with high sensitivity to distinguish HBV/HCV and detect their overlapping infection. Herein, a new biosensor named "hepatitis virus indicator" for simultaneous detection of HBV and HCV based on the automatic particle enumeration was developed by the combination of Exo III assisted signal amplification strategy and particle counting technology with a dark-field microscopy. The limit of detections (LOD) were as low as 0.194 pM for HBV and 0.169 pM for HCV, respectively. In addition, the proposed method was capable of simultaneously detecting HBV and HCV based on the colorful light scattering from plasmonic nanoparticles. The proposed assay was simple, sensitive and selective for the simultaneous detection of HBV and HCV, which provided a new idea for the early diagnosis of diseases, such as hepatitis A virus (HAV), hepatitis D virus (HDV) and hepatitis E virus (HEV).

Size-Dependent Plasmonic Resonance Scattering Characteristics of Gold Nanorods for Highly Sensitive Detection of microRNA-27a.

MicroRNAs, as one kind of significant biomarkers, play indispensable roles in the diagnosis and treatment of cancers. Yet, owing to low expression and high sequence homology, high sensitivity and specificity for microRNA detection are greatly challenging. Herein, a sensitive sensing platform with high specificity was developed for microRNA-27a (miRNA-27a) based on the miRNA-27a-triggered chemical etching of gold nanorods to a smaller size, which was accompanied by a significant blue shift and a large decrease of intensity in the localized surface plasmon resonance (LSPR) scattering and remarkable color variability from red to green. When combined with strand displacement reactions as well as liposome signal amplification and transduction, the proposed bioassay presented high selectivity toward miRNA-27a in a dynamic range from 100 fM to 3 pM and a low limit of detection of 16.5 fM (3σ/k) by dark-field microscopy. Additionally, the remarkable discrimination of single nucleotide difference suggested superior selectivity and was able to detect miRNA-27a extracted from breast cancer cells. The strategy put forward is universal, presenting amusing application prospects in the early diagnosis of various cancers by adapting the corresponding nucleotide sequences.

The synergistic effect enhanced chemical etching of gold nanorods for the rapid and sensitive detection of biomarks.

The rapid and sensitive assay is the goal for advancing analytical methods and techniques to save time and achieve the early diagnosis, which are of crucial importance in clinic. The concept of synergistic effects for fastening reaction and improving sensitivity was constructed by introducing iodide (I-) to the typical Fenton's reaction system as a model reaction, which was calculated theoretically and demonstrated experimentally. In an acid medium, the simultaneous presence of Fe2+ and I- could significantly improve the oxidation capability and rate of H2O2 to etch gold nanorods (AuNRs) because of the synergistic effect, which was further successfully applied to the rapid and sensitive assay of cholesterol, glucose and uric acid in human serum. In this work, the synergistic effect greatly improved the reaction rate and sensitivity, which showed potential applications in biological sensing and clinic diagnosis.

High-Resolution Vertical Polarization Excited Dark-Field Microscopic Imaging of Anisotropic Gold Nanorods for the Sensitive Detection and Spatial Imaging of Intracellular microRNA-21.

As an important biomarker for early diagnosis of cancers, sensitive detection and high-resolution imaging of microRNA-21 in cancer cells have become important and challengeable. In this work, highly sensitive detection and spatial imaging of intracellular microRNA-21 were realized by the reduced signal background through vertical polarization excitation with a polarizer. The lateral local surface plasmon resonance property of gold nanorods (AuNRs) displayed a pronounced green color with low scattering intensity, which was adjusted to red color with strong scattering intensity when the core-satellite gold nanoparticle (AuNP) assembly was constructed on the side of AuNRs through a catalyzed hairpin assembly (CHA) circuit in the presence of microRNA-21. This unique approach allows for effectively reducing the strong background signal to improve the sensitivity of detection. Additionally, the proposed strategy can not only realize the sensitive detection of microRNA-21 with the limit of detection as low as 2 pM (3σ) but also achieve the high spatial imaging of cancer cells, which provided a specific strategy for the construction and imaging of intracellular imaging probes. It is believed that the simple and sensitive approach on the basis of lateral local surface plasmon resonance property of anisotropic AuNRs with excellent sensitivity combined with high spatial imaging holds promising potentials to visualize intracellular microRNAs with low abundance.

Label-free gold nanorods sensor array for colorimetric detection and discrimination of biothiols in human urine samples.

Biothiols play important roles in regulating redox balance in biological systems, but their discrimination is challengeable. In this work, a colorimetric nanosensing array for biothiols was established, which was composed of gold nanorods (AuNRs) and metal ions (Hg2+, Pb2+, Cu2+, Ag+). By employing label-free AuNRs as the colorimetric probe, and the color and spectral changes of AuNRs as the output signal, principal component analysis (PCA) was applied to processing the signal and generating a clustering map. Due to the different binding affinity between biothiols and metal ions, AuNRs exhibited a unique pattern to form a fingerprint-like colorimetric array, which was able to discriminate five biothiols by the naked eyes. This strategy combines PCA and sensor array to achieve rapid and accurate discrimination and detection of biothiols. In addition, the method shows the great potential in analysis of biothiols in human urine samples.

Chinese nurses are at high risk for suicide: A review of nurses suicide in China 2007-2016.

OBJECTIVE: This study summarized the cases of Chinese nurses' suicide during 2007-2016. METHODS: We reviewed public reports on local media, and medical websites. RESULT: A total of 46 cases of nurse suicide reported or published from 2007 to 2016. In these 46 cases, the proportion of female suicide is 98%. Most cases of suicide occurred in nurses aged 18-50 years. The most common way of suicide was jump from building. Nurse suicide occurred more often in full-service tertiary hospitals. CONCLUSION: The Chinese Government and medical organization should be aware of severity of suicide, and take action to be avoided of more suicide in Chinese nurses.