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Fang, Chiew San,Kim, Kwang-sun,Yu, Byeongjun,Jon, Sangyong,Kim, Moon-Soo,Yang, Haesik American Chemical Society 2017 ANALYTICAL CHEMISTRY - Vol.89 No.3
<P>Both high sensitivity and high specificity are crucial for detection of miRNAs that have emerged as important clinical biomarkers. Just Another Zinc finger proteins (JAZ, ZNF346) bind preferably (but nonsequence-specifically) to DNA RNA hybrids over single stranded RNAs, single stranded DNAs, and double stranded DNAs. We present an ultrasensitive and highly specific electrochemical method for miRNA-21 detection based on the selective binding of JAZ to the DNA RNA hybrid formed between a DNA capture probe and a target miRNA-21. This enables us to use chemically stable DNA as a capture probe instead of RNA as well as to apply a standard sandwich type assay format to miRNA detection. High signal amplification is obtained by (i) enzymatic amplification by alkaline phosphatase (ALP) coupled with (ii) electrochemical chemical chemical (ECC) redox cycling involving an ALP product (hydroquinone). Low nonspecific adsorption of ALP conjugated JAZ is obtained using a polymeric self-assembled-monolayer-modified and casein treated indium tin oxide electrode. The detection method can discriminate between target miRNA-21 and nontarget nucleic acids (DNA DNA hybrid, single stranded DNA, miRNA-125b, miRNA-155, single base mismatched miRNA, and three base mismatched miRNA). The detection limits for miRNA-21 in buffer and 10 fold diluted serum are approximately 2 and 30 fM, respectively, indicating that the detection method is ultrasensitive. This detection method can be readily extended to multiplex detection of miRNAs with only one ALP conjugated JAZ probe due to its nonsequence-specific binding character. We also believe that the method could offer a promising solution for point of care testing of miRNAs in body fluids.</P>
Fang, Chiew San,Oh, Kyung Hwan,Oh, Aram,Lee, Kwangyeol,Park, Seonhwa,Kim, Sinyoung,Park, Jin Kyoon,Yang, Haesik The Royal Society of Chemistry 2016 Chemical communications Vol.52 No.34
<P>This communication reports a new nanocatalytic scheme based on the facts that the redox reaction between a highly outer-sphere-reaction-philic (OSR-philic) species and a highly inner-sphere-reaction-philic (ISR-philic) species is slow and that an OSR-and ISR-philic Au-nanocatalyst label can mediate the two different types of redox species. This scheme allows highly sensitive and incubation free detection of creatine kinase-MB.</P>
Washing-Free Electrochemical Detection of Amplified Double-Stranded DNAs Using a Zinc Finger Protein
Fang, Chiew San,Kim, Kwang-sun,Ha, Dat Thinh,Kim, Moon-Soo,Yang, Haesik American Chemical Society 2018 ANALYTICAL CHEMISTRY - Vol.90 No.7
<P>Recombinase polymerase amplification (RPA) has been combined with electrochemical detection for simple and rapid point-of-care testing. However, there are two major hindrances to this simple and rapid testing: (i) washing or purification steps are required to remove unbound labeled probes and interfering species in the sample; (ii) it is difficult to quantify double-stranded DNA (dsDNA) electrochemically by using biospecific affinity binding without dsDNA denaturation. In the present study, we describe a wash-free and rapid electrochemical method to detect RPA-amplified dsDNAs using a zinc finger protein, Zif268. Electrochemical detection is achieved using proximity-dependent electron mediation of ferrocenemethanol between a glucose-oxidase (GOx) label and an electrode, which differentiates the specifically electrode-bound and -unbound labels without a washing or purification step. RPA-amplified dsDNA containing a biotin-terminated forward primer is specifically bound to a neutravidin-modified electrode, and GOx-conjugated Zif268 is specifically bound to the dsDNA. The whole detection is performed within 17 min (15 min for the RPA reaction and <2 min for the electrochemical measurement). Electrochemical detection is carried out without an additional incubation period, because the specific binding between Zif268 and the dsDNA occurs during the RPA reaction. The detection method could discriminate between target template DNA of <I>Piscirickettsia salmonis</I> and nontarget DNAs (random sequence and calf thymus DNA). The detection limit for the target DNA is approximately 300 copies in 13.2 μL, indicating that the detection method is ultrasensitive. We believe that the method could offer a promising solution for simple and rapid point-of-care testing.</P> [FIG OMISSION]</BR>
ON POSITIVE DEFINITE SOLUTIONS OF A CLASS OF NONLINEAR MATRIX EQUATION
Fang, Liang,Liu, San-Yang,Yin, Xiao-Yan Korean Mathematical Society 2018 대한수학회보 Vol.55 No.2
This paper is concerned with the positive definite solutions of the nonlinear matrix equation $X-A^*{\bar{X}}^{-1}A=Q$, where A, Q are given complex matrices with Q positive definite. We show that such a matrix equation always has a unique positive definite solution and if A is nonsingular, it also has a unique negative definite solution. Moreover, based on Sherman-Morrison-Woodbury formula, we derive elegant relationships between solutions of $X-A^*{\bar{X}}^{-1}A=I$ and the well-studied standard nonlinear matrix equation $Y+B^*Y^{-1}B=Q$, where B, Q are uniquely determined by A. Then several effective numerical algorithms for the unique positive definite solution of $X-A^*{\bar{X}}^{-1}A=Q$ with linear or quadratic convergence rate such as inverse-free fixed-point iteration, structure-preserving doubling algorithm, Newton algorithm are proposed. Numerical examples are presented to illustrate the effectiveness of all the theoretical results and the behavior of the considered algorithms.
On positive definite solutions of a class of nonlinear matrix equation
Liang Fang,San-Yang Liu,Xiaoyan Yin 대한수학회 2018 대한수학회보 Vol.55 No.2
This paper is concerned with the positive definite solutions of the nonlinear matrix equation $X-A^{*}\bar{X}^{-1}A=Q$, where $A, Q$ are given complex matrices with $Q$ positive definite. We show that such a matrix equation always has a unique positive definite solution and if $A$ is nonsingular, it also has a unique negative definite solution. Moreover, based on Sherman-Morrison-Woodbury formula, we derive elegant relationships between solutions of $X-A^{*}\bar{X}^{-1}A=I$ and the well-studied standard nonlinear matrix equation $Y+B^{*}Y^{-1}B=Q$, where $B, Q$ are uniquely determined by $A$. Then several effective numerical algorithms for the unique positive definite solution of $X-A^{*}\bar{X}^{-1}A=Q$ with linear or quadratic convergence rate such as inverse-free fixed-point iteration, structure-preserving doubling algorithm, Newton algorithm are proposed. Numerical examples are presented to illustrate the effectiveness of all the theoretical results and the behavior of the considered algorithms.
Identification of Homer1 as a Potential Prognostic Marker for Intrahepatic Cholangiocarcinoma
Wu, San-Yun,Yu, Ming-Xia,Li, Xiao-Gai,Xu, Shu-Fang,Shen, Ji,Sun, Zhen,Zhou, Xin,Chen, Xing-Zhen,Tu, Jian-Cheng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7
Background: The aim of the present study was to analyze whether Homer1 is a potential prognostic marker for intrahepatic cholangiocarcinoma (ICC). Materials and Methods: The expression of Homer1 in ICC tissue was detected with immunohistochemistry and levels of protein in ICC and paratumor tissues were evaluated by Western blotting. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. Results: Homer1 expression was high in 67.4% (58/86) of ICC samples, and there was significant difference between ICC and adjacent noncancerous tissues (p<0.001); high expression was associated with poor histologic differentiation (p=0.019), TNM stage (p=0.014), lymph node metastasis (p=0.040), and lymphatic invasion (p=0.025). On Kaplan-Meier analysis, a comparison of survival curves of low versus high expressors of Homer1 revealed a highly significant difference in OS (p=0.001) and DFS (p=0.006), indicating that high expression of Homer1 was linked with a worse prognosis. Multivariate analyses showed that Homer1 expression was an independent risk factor predicting overall survival[Hazard ratio(HR), 7.52; 95% confidence interval (CI), 2.63-21.47; p=0.002] and disease-free survival (HR, 11.56; 95%CI, 5.17-25.96; p<0.001) in ICC. Conclusions: Homer1 promotes lymphatic invasion and associates with lymph node metastasis and poor prognosis of ICC. The current study shows that Homer1 may be an independent prognostic factor for ICC patients after curative resection, and it provides an important basis for screening/treating high-risk patients.