Xiaoyuan Chen

Bio: Xiaoyuan Chen is an academic researcher from National University of Singapore. The author has contributed to research in topics: Physics & Photothermal therapy. The author has an hindex of 149, co-authored 994 publications receiving 89870 citations. Previous affiliations of Xiaoyuan Chen include Brown University & University of Southern California.

Noninvasive Visualization of MicroRNA-16 in the Chemoresistance of Gastric Cancer Using a Dual Reporter Gene Imaging System

Abstract: MicroRNAs (miRNAs) have been implicated to play a central role in the development of drug resistance in a variety of malignancies. However, many studies were conducted at the in vitro level and could not provide the in vivo information on the functions of miRNAs in the anticancer drug resistance. Here, we introduced a dual reporter gene imaging system for noninvasively monitoring the kinetic expression of miRNA-16 during chemoresistance in gastric cancer both in vitro and in vivo. Human sodium iodide symporter (hNIS) and firefly luciferase (Fluc) genes were linked to form hNIS/Fluc double fusion reporter gene and then generate human gastric cancer cell line NF-3xmir16 and its multidrug resistance cell line NF-3xmir16/VCR. Radioiodide uptake and Fluc luminescence signals in vitro correlated well with viable cell numbers. The luciferase activities and radioiodide uptake in NF-3xmir16 cells were remarkably repressed by exogenous or endogenous miRNA-16. The NF-3xmir16/VCR cells showed a significant increase of 131I uptake and luminescence intensity compared to NF-3xmir16 cells. The radioactivity from in vivo 99mTc-pertechnetate imaging and the intensity from bioluminescence imaging were also increased in NF-3xmir16/VCR compared with that in NF-3xmir16 tumor xenografts. Furthermore, using this reporter gene system, we found that etoposide (VP-16) and 5-fluorouracil (5-FU) activated miRNA-16 expression in vitro and in vivo, and the upregulation of miRNA-16 is p38MAPK dependent but NF-κB independent. This dual imaging reporter gene may be served as a novel tool for in vivo imaging of microRNAs in the chemoresistance of cancers, as well as for early detection and diagnosis in clinic.

Desmin- and vimentin-mediated hepatic stellate cell-targeting radiotracer 99mTc-GlcNAc-PEI for liver fibrosis imaging with SPECT.

Abstract: Extracellular matrix (ECM) accumulation in liver fibrosis is caused by the activation of hepatic stellate cells (HSCs). The goal of this study was to develop a 99mTc-labeled N-acetylglucosamine (GlcNAc) that specifically interacts with desmin and vimentin expressed on activated HSCs to monitor the progression and prognosis of liver fibrosis using single-photon emission computed tomography (SPECT) imaging. Methods: GlcNAc-conjugated polyethylenimine (PEI) was first prepared and radiolabeled with 99mTc. Noninvasive SPECT imaging with 99mTc-GlcNAc-PEI was used to assess liver fibrosis in a carbon tetrachloride (CCl4) mouse model. The liver uptake value (LUV) of 99mTc-GlcNAc-PEI was measured by drawing the region of interest (ROI) of the whole liver as previously suggested. The LUV of the CCl4 groups was compared with that of the olive oil group. Next, we estimated the correlation between the results of SPECT imaging and physiological indexes. After treatment with clodronate liposome, the LUV of 99mTc-GlcNAc-PEI in fibrotic mice was compared with that in control mice. Results:99mTc-GlcNAc-PEI is a hydrophilic compound with high radiochemical purity (>98%) and good stability. It could specifically target desmin and vimentin on the surface of activated HSCs with high affinity (the Kd values were 53.75 ± 9.50 nM and 20.98 ± 3.56 nM, respectively). The LUV of 99mTc-GlcNAc-PEI was significantly different between the CCl4 and control groups as early as 4 weeks of CCl4 administration (3.30 ± 0.160 vs 2.34 ± 0.114%/cc; P ˂ 0.05). There was a strong correlation between the LUV and Sirius Red quantification (R = 0.92, P ˂ 0.001). Compared with control, clodronate liposome treatment reduced the LUV of 99mTc-GlcNAc-PEI (4.62 ± 0.352 vs 2.133 ± 0.414%/cc; P ˂ 0.05). Conclusion:99mTc-GlcNAc-PEI SPECT/CT was useful in assessing liver fibrosis and monitoring the treatment response.

Synthesis of (4-[18F]fluorophenyl)triphenylphosphonium as a potential imaging agent for mitochondrial dysfunction

Abstract: Tetraphenylphosphonium (TPP) cation is able to function as a molecular probe for monitoring mitochondrial disease. The F-18 labeled TPP, (4-[18F]fluorophenyl) triphenylphosphonium (18FTPP), was therefore developed as a PET radioligand for in vivo molecular imaging of mitochondrial dysfunction. 18FTPP was synthesized via direct nucleophilic substitution of no-carrier-added [18F]fluoride with the precursor 4-nitrophenyltriphenylphosphonium. After purification by HPLC, the average radiochemical yield was determined to be 10–15% and the specific activity was >500 Ci/mmol at the end of synthesis. The total synthesis time was within 60 min, and the radiochemical purity of the 18FTPP was above 95%. Copyright © 2005 John Wiley & Sons, Ltd.

Exceedingly Small Gadolinium Oxide Nanoparticles with Remarkable Relaxivities for Magnetic Resonance Imaging of Tumors.

Abstract: Gd chelates have occupied most of the market of magnetic resonance imaging (MRI) contrast agents for decades. However, there have been some problems (nephrotoxicity, non-specificity, and low r1 ) that limit their applications. Herein, a wet-chemical method is proposed for facile synthesis of poly(acrylic acid) (PAA) stabilized exceedingly small gadolinium oxide nanoparticles (ES-GON-PAA) with an excellent water dispersibility and a size smaller than 2.0 nm, which is a powerful T1 -weighted MRI contrast agent for diagnosis of diseases due to its remarkable relaxivities (r1 = 70.2 ± 1.8 mM-1 s-1 , and r2 /r1 = 1.02 ± 0.03, at 1.5 T). The r1 is much higher and the r2 /r1 is lower than that of the commercial Gd chelates and reported gadolinium oxide nanoparticles (GONs). Further ES-GON-PAA is developed with conjugation of RGD2 (RGD dimer) (i.e., ES-GON-PAA@RGD2) for T1 -weighted MRI of tumors that overexpress RGD receptors (i.e., integrin αv β3 ). The maximum signal enhancement (ΔSNR) for T1 -weighted MRI of tumors reaches up to 372 ± 56% at 2 h post-injection of ES-GON-PAA@RGD2, which is much higher than commercial Gd-chelates (<80%). Due to the high biocompatibility and high tumor accumulation, ES-GON-PAA@RGD2 with remarkable relaxivities is a promising and powerful T1 -weighted MRI contrast agent.

Reducing false negatives in COVID-19 testing by using microneedle-based oropharyngeal swabs.

Abstract: Summary Coronavirus disease 2019 (COVID-19) has become a severe threat to human health worldwide. Early etiological diagnosis plays a critical role in controlling COVID-19 pandemic. However, etiological diagnosis has been largely compromised by high “false-negative” rates of viral nucleic acid testing, resulting from limited sampling efficiency using conventional oropharyngeal swabs. Here, we engineer regular swabs by using a microneedle (MN) patch to significantly improve the quality and quantity of virus collection. The combination of MNs with different crosslinking levels endows the patches with dual capability of mucus penetration and virus extraction. Moreover, the antibody (Ab) against viral spike protein was integrated into the patch, conferring MNs with an active virus capture potential. By taking advantage of the biological and engineered species, we believe that the designed MN/Ab swabs could serve as a promising tool to improve current sampling efficiency with fewer false negatives, contributing to the containment of the COVID-19 pandemic.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Chemistry and properties of nanocrystals of different shapes.

Abstract: The interest in nanoscale materials stems from the fact that new properties are acquired at this length scale and, equally important, that these properties * To whom correspondence should be addressed. Phone, 404-8940292; fax, 404-894-0294; e-mail, mostafa.el-sayed@ chemistry.gatech.edu. † Case Western Reserve UniversitysMillis 2258. ‡ Phone, 216-368-5918; fax, 216-368-3006; e-mail, burda@case.edu. § Georgia Institute of Technology. 1025 Chem. Rev. 2005, 105, 1025−1102