Publications by authors named "Zixiang Wang"

32 Publications

Osteoporosis and Endplate Damage Correlation Using a Combined Approach of Hounsfield Unit Values and Total Endplate Scores: A Retrospective Cross-Sectional Study.

Clin Interv Aging 2021 5;16:1275-1283. Epub 2021 Jul 5.

Department of Orthopedics, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

Purpose: Osteoporosis and endplate damage, two primary orthopedic disorders that have adverse effects on the quality of life of older adults, may have some previously unknown relationship. The purpose of this study was to determine the potential association between osteoporosis and endplate damage with two specific imaging scoring systems and analyze the underlying mechanisms.

Patients And Methods: A cross-sectional study including 156 patients with degenerative disc disease (DDD) who visited our department in 2018 was performed. Data including age, sex, body mass index, Hounsfield unit (HU) values utilizing computed tomography (CT), and total endplate scores (TEPSs) using magnetic resonance imaging (MRI) of all patients were retrospectively collected and analyzed. The average HU value and TEPS of L1-L4 were used to represent the degrees of bone mineral density (BMD) and endplate damage, respectively. Patients with an HU value < 110 were defined as having osteoporosis and placed in the low-BMD group; otherwise, they were placed in the normal-BMD group. Multivariate logistic regression models were used to determine the independent factors of endplate damage.

Results: The TEPSs in the low-BMD group were significantly higher (6.4 ± 1.6 vs 5.0 ± 0.9, p < 0.001) overall and in every segment of L1-L4 (p < 0.01). A significant negative correlation was found between TEPS and HU values (p < 0.001). The HU value (odds ratio [OR] 0.221; 95% confidence interval [CI], 0.148-0.295, p < 0.001), age (OR 0.047; 95% CI, 0.029-0.224, p < 0.001), and BMD (OR 3.796; 95% CI, 2.11-7.382, p < 0.05) were independent factors influencing endplate damage.

Conclusion: A significantly positive correlation was observed between osteoporosis and endplate damage, indicating the requirement for a more comprehensive therapeutic regimen for treating patients with DDD complicated with osteoporosis.
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http://dx.doi.org/10.2147/CIA.S315213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275111PMC
July 2021

EVI1 overexpression promotes ovarian cancer progression by regulating estrogen signaling.

Mol Cell Endocrinol 2021 Aug 17;534:111367. Epub 2021 Jun 17.

Department of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China. Electronic address:

High-grade serous ovarian cancer (HGSOC) is characterized by TP53 mutation and somatic copy number alterations (SCNAs). Here we show that the oncogenic transcription factor EVI1 (ecotropic viral integration site-1) is amplified and overexpressed up to 30% of 1640 HGSOC cases in The Cancer Genome Atlas (TCGA). Functionally, EVI1 promotes proliferation/invasion in vitro and tumor growth of xenograft model in vivo. Importantly, we discover that EVI1 regulates estrogen signaling by directly activating ESR1 (estrogen receptor 1) transcription determined by the ChIP and luciferase assay. Interestingly, EVI1 and ESR1 share common regulatory targets as indicated by the analysis of ChIP-Seq data. EVI1 and ESR1 collaborate in the regulation of some estrogen receptor-regulated genes. Furthermore, EVI1 drives tumor aggressiveness partially by regulating estrogen signaling. Estrogen enhances the proliferation, invasion and xenograft growth of ovarian cancer cells. Importantly, estrogen can rescue the inhibition of proliferation, invasion and xenograft growth induced by silencing EVI1. These findings suggest that EVI1 functions as a novel regulator of the estrogen signaling network in ovarian cancer.
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http://dx.doi.org/10.1016/j.mce.2021.111367DOI Listing
August 2021

The East Asian Erotic Picture Dataset and Gender Differences in Response to Opposite-Sex Erotic Stimuli in Chinese College Students.

Front Psychol 2021 21;12:648271. Epub 2021 Apr 21.

Reward, Competition and Social Neuroscience Lab, Department of Psychology, School of Social and Behavioral Sciences, Nanjing University, Nanjing, China.

Understanding the processing of sexual stimuli has become a significant part of research on human sexuality. In addition to individual characteristics (gender and sexual orientation), empirical studies have shown that cultural factors play an important role in sexual stimuli processing. The attitudes toward sex have been reported to be more conservative in East Asian societies as compared to western countries, and significantly more sexual difficulties are observed among East Asian people. However, stimulus materials, which potentially facilitate human sexuality research on native East Asian people, are relatively not satisfactory. Erotic stimuli depicting East Asian figures are limited in the existing picture datasets. To address this issue, we present a collection of 237 erotic and 108 control pictures, accompanied by self-reported ratings of sexual arousal, pleasantness, and sexual attractiveness for opposite-sex erotic stimuli by heterosexual males and females ( = 40, divided into two equal-sized subsamples). This collection is divided into six categories, depending on their contents: dressed males (44), semi-nude males (65), nude males (64), dressed females (64), semi-nude females (52), and nude females (56). We showed gender differences in sexual arousal, pleasantness, and sexual attractiveness ratings in response to opposite-sex erotic pictures. Males reported the highest levels of sexual arousal, pleasantness, and sexual attractiveness for nude female pictures, whereas females reported the highest levels of sexual arousal, pleasantness, and sexual attractiveness for semi-nude male pictures. The erotic picture dataset may provide a useful resource of erotic stimuli that can be used as stimulus materials in experimental research on sexual function in East Asians.
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http://dx.doi.org/10.3389/fpsyg.2021.648271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096987PMC
April 2021

Splicing factor USP39 promotes ovarian cancer malignancy through maintaining efficient splicing of oncogenic HMGA2.

Cell Death Dis 2021 03 17;12(4):294. Epub 2021 Mar 17.

Key Laboratory of Experimental Teratology, Ministry of Education, Department of Cell Biology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.

Aberrant expression of splicing factors was found to promote tumorigenesis and the development of human malignant tumors. Nevertheless, the underlying mechanisms and functional relevance remain elusive. We here show that USP39, a component of the spliceosome, is frequently overexpressed in high-grade serous ovarian carcinoma (HGSOC) and that an elevated level of USP39 is associated with a poor prognosis. USP39 promotes proliferation/invasion in vitro and tumor growth in vivo. Importantly, USP39 was transcriptionally activated by the oncogene protein c-MYC in ovarian cancer cells. We further demonstrated that USP39 colocalizes with spliceosome components in nuclear speckles. Transcriptomic analysis revealed that USP39 deletion led to globally impaired splicing that is characterized by skipped exons and overrepresentation of introns and intergenic regions. Furthermore, RNA immunoprecipitation sequencing showed that USP39 preferentially binds to exon-intron regions near 5' and 3' splicing sites. In particular, USP39 facilitates efficient splicing of HMGA2 and thereby increases the malignancy of ovarian cancer cells. Taken together, our results indicate that USP39 functions as an oncogenic splicing factor in ovarian cancer and represents a potential target for ovarian cancer therapy.
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http://dx.doi.org/10.1038/s41419-021-03581-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969951PMC
March 2021

Enhanced Isolation of Fetal Nucleated Red Blood Cells by Enythrocyte-Leukocyte Hybrid Membrane-Coated Magnetic Nanoparticles for Noninvasive Pregnant Diagnostics.

Anal Chem 2021 01 9;93(2):1033-1042. Epub 2020 Dec 9.

Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China.

Fetal nucleated red blood cells (fNRBCs) in maternal peripheral blood containing the whole genetic information of the fetus may serve for noninvasive pregnant diagnostics (NIPD). However, the fetal cell-based NIPD is seriously limited by the poor purity of the isolated fNRBCs. Recently, the biomimetic cell membrane-camouflaged nanoparticles containing outstanding features have been widely used to detect and isolate rare cells from the peripheral blood samples. In this work, enythrocyte (RBC) and leukocyte (WBC) membranes are fused and coated onto magnet nanoparticles and then modified with anti-CD147 to isolate fNRBCs from the maternal peripheral blood with significant efficiency (∼90%) and purity (∼87%) in simulated spiked blood samples. Further, fNRBCs were isolated and identified from a series of maternal peripheral blood samples coming from pregnant women of 11-13 gestational weeks, and different chromosomal aneuploidies were diagnosed using fNRBCs isolated from maternal blood in early pregnancy. Our strategy may offer additional opportunity to overcome the limitations of current cell-based NIPD platforms.
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http://dx.doi.org/10.1021/acs.analchem.0c03933DOI Listing
January 2021

High-throughput isolation of fetal nucleated red blood cells by multifunctional microsphere-assisted inertial microfluidics.

Biomed Microdevices 2020 10 20;22(4):75. Epub 2020 Oct 20.

Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, 430072, China.

Being easy, safe and reliable, non-invasive prenatal diagnosis (NIPD) has been greatly pursued in recent years. Holding the complete genetic information of the fetus, fetal nucleated red blood cells (fNRBCs) are viewed as a suitable target for NIPD application. However, effective separating fNRBCs from maternal peripheral blood for clinic use still faces great challenges, given that fNRBCs are extremely rare in maternal blood circulation. Here, by combining the high-throughput inertial microfluidic chip with multifunctional microspheres as size amplification, we develop a novel method to isolate fNRBCs with high performance. To enlarge the size difference between fNRBCs and normal blood cells, we use the gelatin coated microspheres to capture fNRBCs with anti-CD147 as specific recognizer at first. The size difference between fNRBCs captured by the microspheres and normal blood cells makes it easy to purify the captured fNRBCs through the spiral microfluidic chip. Finally, the purified fNRBCs are mildly released from the microspheres by enzymatically degrading the gelatin coating. Cell capture efficiency about 81%, high purity of 83%, as well as cell release viability over 80% were achieved using spiked samples by this approach. Additionally, fNRBCs were successfully detected from peripheral blood of pregnant women with an average of 24 fNRBCs per mL, suggesting the great potential of this method for clinical non-invasive prenatal diagnosis.
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http://dx.doi.org/10.1007/s10544-020-00531-2DOI Listing
October 2020

Electrospun degradable Zn-Mn oxide hierarchical nanofibers for specific capture and efficient release of circulating tumor cells.

Nanotechnology 2020 Dec;31(49):495102

Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, Hubei 430072, People's Republic of China.

Constructing biological affinity devices is considered as an effective strategy for isolating circulating tumor cells (CTCs), and electrospun nanofibers (ESNFs) have recently received attention. However, the current research focuses on polymer fibers, and fabricating stimuli-responsive inorganic nanofibers for cancer diagnosis and analysis is still challenging. In this work, Zn-Mn oxide nanofibers (ZnMnNFs) are used to capture and purify cancer cells after modification with specific antibodies. Then, the hierarchical nanofibers are degraded by reductive weak acid to release the captured cells efficiently without residues. Fusion of Zn and Mn, two transition metals, enhances the surface activity of oxides so that ZnMnNFs are easier to be degraded and modified. By using MCF-7 cancer cells, the cell capture efficiency of ZnMnNFs is up to 88.2%. Furthermore, by using citric acid, it is discovered that, by comparison with Mn oxide nanofibers, the cell release efficiency of ZnMnNFs is improved to 95.1% from 15.4%. In addition, the viability of released cells exceeds 90%. Lastly, the robustness of ZnMnNFs substrates is tested in peripheral blood from breast cancer patients (BCP) and colorectal cancer patients (CCP). Combined with fluorescence labeling, CTCs are confirmed to be isolated from all the clinical samples. This is the first trial of using ternary inorganic ESNFs for cancer cell capture. It is anticipated that the degradable ESNFs will provide biocompatible theranostic platforms and overcome the current limitations of cell release for high-precision gene analysis.
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http://dx.doi.org/10.1088/1361-6528/abb48bDOI Listing
December 2020

Cyclin F and KIF20A, FOXM1 target genes, increase proliferation and invasion of ovarian cancer cells.

Exp Cell Res 2020 10 7;395(2):112212. Epub 2020 Aug 7.

Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China. Electronic address:

Increased expression of FOXM1 is observed in a variety of human malignancies. The downstream target genes of FOXM1 involved in tumorigenesis and development are not fully elucidated in ovarian cancer. Here, we identified Cyclin F, a substrate recognition subunit of SCF (Skp1-Cul1-F-box protein) complex, and Kinesin Family Member 20A (KIF20A) were transcriptionally regulated by FOXM1 in ovarian cancer. Accordingly, Cyclin F and KIF20A were commonly overexpressed in ovarian cancer. Functionally, forced expression of Cyclin F or KIF20A significantly enhanced while knockdown of them decreased proliferation and invasion of ovarian cancer cells. Importantly, high levels of Cyclin F and KIF20A correlated with poor prognosis in patients with ovarian cancer. Our findings indicate that Cyclin F and KIF20A are functional targets of FOXM1 which might be potential drug targets in ovarian cancer.
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http://dx.doi.org/10.1016/j.yexcr.2020.112212DOI Listing
October 2020

Altered sulcogyral patterns of orbitofrontal cortex in patients with mild cognitive impairment.

Psychiatry Res Neuroimaging 2020 08 21;302:111108. Epub 2020 May 21.

Reward, Competition and Social Neuroscience Lab, Department of Psychology, School of Social and Behavioral Sciences, Nanjing University, Nanjing, China; Institute for Brain Sciences, Nanjing University, Nanjing, China. Electronic address:

Mild cognitive impairment (MCI) is increasingly recognized as a risk factor for Alzheimer's disease (AD). Neuroimaging studies have revealed structural abnormalities in the orbitofrontal cortex (OFC) in MCI patients, while other findings fail to report anatomical alterations. Accordingly, structural changes in this brain region amongst MCI patients has not been well characterized. Given that OFC sulcogyral organization has increasingly been demonstrated as a reliable pre-morbid marker of pathological conditions in several neuropsychiatric disorders, we examined the distribution of OFC sulcogyral patterns (classified into Type I, II and III) based on structural brain data from 68 MCI patients and 55 healthy controls. Our results, supported by both Frequentist and Bayesian statistics, showed that MCI patients exhibited an increased prevalence of Type II pattern compared with healthy controls, particularly in the right hemisphere. Meanwhile, MCI patients showed a decreased prevalence of Type I pattern compared with healthy controls. Taken together, our results reveal a skewed distribution of OFC sulcogyral in MCI patients, possibly reflecting a potential neurodevelopmental risk marker of MCI.
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http://dx.doi.org/10.1016/j.pscychresns.2020.111108DOI Listing
August 2020

ZnO nanowire-integrated bio-microchips for specific capture and non-destructive release of circulating tumor cells.

Nanoscale 2020 Jan;12(3):1455-1463

Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, 430072, Hubei, P. R. China.

Circulating tumor cells (CTCs) are one type of significant biomarker in cancer patients' blood that have been attracting attention from researchers for decades, and their efficient and viable isolation is of vital importance in cancer prevention and treatment. However, the development of efficient and low-cost bio-microchips still faces significant challenges. In this paper, we construct a novel three-dimensional micro-nano bio-microchip that has dual functions of specifically capturing and non-destructively releasing cancer cells. ZnO nanowire arrays were vertically grown on the surface of a polydimethylsiloxane (PDMS) pillar substrate with a gear structure (ZnO-coated G-PDMS pillar microchips). The gear structure provides more binding sites for antibodies and target cancer cells, while ZnO nanowires provide a rough surface for CTC attachment and size-specific effects for retaining CTCs. For subsequent culture and bioanalysis, the captured CTCs can be non-destructively released with high efficiency and good viability using a mild acidic solution treatment. Furthermore, the manufacturing process of the G-PDMS pillar microchips is convenient and low-cost, and the preparation approach of the ZnO nanowire is mature and simple to operate. In particular, the bio-microchips showed high capture efficiency (91.11% ± 5.53%) and excellent cell viability (96%) using a spiked cell sample. Moreover, we successfully achieved the specific fluorescent labeling of CTCs in 9 clinical breast cancer patients' samples. The ZnO-coated G-PDMS pillar microchips not only have great potential for new target drug development for cancer stem cells but also open up new opportunities for individualized treatment.
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http://dx.doi.org/10.1039/c9nr07349cDOI Listing
January 2020

Silica microbeads capture fetal nucleated red blood cells for noninvasive prenatal testing of fetal ABO genotype.

Electrophoresis 2020 06 8;41(10-11):966-972. Epub 2020 Jan 8.

Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P. R. China.

ABO hemolytic disease of the newborn (ABO-HDN), which may cause neonatal jaundice and polycythemia, or even stillbirth or neonatal death, is widespread in China. Prenatal testing for the fetal ABO blood group can reduce unnecessary concerns or ensure prompt treatment. Herein, we presented a method to employ high-density silica microbeads (SiO MBs) for capturing fetal nucleated red blood cells (fnRBCs) in maternal peripheral blood, and we detected the ABO genotype of the fetus using these captured cells. We evaluated 52 patients using the SiO MBs. Among 26 pregnant women with type O blood, 8 (30.8%) of the fetuses had type A blood, 5 (19.2%) had type B blood, and 13 (50%) had type O blood. SRY genes were detected in all 27 male fetuses. This study represents a simple and effective method for noninvasive prenatal detection of the fetal ABO genotype. We believe that this method has great potential for noninvasive prenatal testing of the fetal Rh blood group and other fetal diseases as well.
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http://dx.doi.org/10.1002/elps.201900292DOI Listing
June 2020

Efficient Delivery of Therapeutic siRNA by FeO Magnetic Nanoparticles into Oral Cancer Cells.

Pharmaceutics 2019 Nov 17;11(11). Epub 2019 Nov 17.

Department of Stem Cells and Regenerative Medicine, Key Laboratory of Cell Biology, National Health Commission of China, and Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, China.

The incidence of oral cancer is increasing due to smoking, drinking, and human papillomavirus (HPV) infection, while the current treatments are not satisfactory. Small interfering RNA (siRNA)-based therapy has brought hope, but an efficient delivery system is still needed. Here, polyethyleneimine (PEI)-modified magnetic FeO nanoparticles were prepared for the delivery of therapeutic siRNAs targeting B-cell lymphoma-2 (BCL2) and Baculoviral IAP repeat-containing 5 (BIRC5) into Ca9-22 oral cancer cells. The cationic nanoparticles were characterized by transmission electronic microscopy (TEM), scanning electronic microscopy (SEM), dynamic light scattering (DLS), and vibrating sample magnetometer (VSM). By gel retardation assay, the nanoparticles were found to block siRNA in a concentration-dependent manner. The cellular uptake of the nanoparticle/siRNA complexes under a magnetic field was visualized by Perl's Prussian blue staining and FAM labeling. High gene silencing efficiencies were determined by quantitative real-time PCR and western blotting. Furthermore, the nanoparticle-delivered siRNAs targeting BCL2 and BIRC5 were found to remarkably inhibit the viability and migration of Ca9-22 cells, by cell counting kit-8 assay and transwell assay. In this study, we have developed a novel siRNA-based therapeutic strategy targeting BCL2 and BIRC5 for oral cancer.
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http://dx.doi.org/10.3390/pharmaceutics11110615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921101PMC
November 2019

An Acoustic Droplet-Induced Enzyme Responsive Platform for the Capture and On-Demand Release of Single Circulating Tumor Cells.

ACS Appl Mater Interfaces 2019 Nov 25;11(44):41118-41126. Epub 2019 Oct 25.

Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology , Wuhan University , Wuhan 430072 , China.

The recovery of rare single circulating tumor cells (CTCs) from patients has great potential to facilitate the study of cell heterogeneity and cancer metastasis, which may promote the development of individualized cancer immunotherapy. Herein, a versatile single-cell recovery approach that utilizes an acoustic droplet-induced enzyme responsive platform for the capture and on-demand release of single CTCs is proposed. The platform combines a multifunctional enzyme-responsive gelatin nanoparticle (GNP)-decorated substrate (GNP-chip) for specific capture with an acoustic droplet positioning technique to realize on-demand release of single CTCs. The acoustic droplet dispenser is employed to generate oxidized alginate microdroplets containing the MMP-9 enzyme (OA-MMP-9) with controllable size and precise positioning upon the cell-attached GNP-chip, allowing controlled cell-surface biodegradation under enzymatic reactions followed by calcium chloride (CaCl) solution treatment to form single-cell encapsulated calcium alginate hydrogels. Benefitting from the existence of hydrogels, the released cells could be efficiently recovered by microcapillary. Results demonstrate that the encapsulated cells maintain good cell morphology in the hydrogels, which allow further single-cell nucleic acid analysis. As a proof-of-concept platform, this approach enables reliable and efficient retrieval of single CTCs and holds the potential for versatility in single-cell analysis systems.
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http://dx.doi.org/10.1021/acsami.9b16566DOI Listing
November 2019

Prognostic significance of mRNA expression of CASPs in gastric cancer.

Oncol Lett 2019 Nov 5;18(5):4535-4554. Epub 2019 Sep 5.

Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.

Current studies suggest that the cysteinyl aspartate specific proteinase (caspase/CASP) family may be closely associated with apoptosis. Scientists have suggested that caspases may be a key to the development of more effective anti-cancer therapies. However, the prognostic value of CASP expression in gastric cancer (GC) remains unclear. Using a Kaplan-Meier plotter online database, the predictive prognostic significance of the expression of 12 CASPs genes (CASP1, CASP2, CASP3, CASP4, CASP5, CASP6, CASP7, CASP8, CASP9, CASP10, CASP12 and CASP14) to overall survival (OS) in different clinicopathological features, including Lauren classification, pathological stages, therapies employed and differentiation in gastric cancer patients was explored. The present study revealed that higher CASP1, 2, 3, 4, 5, 6, 7 and 8 mRNA expression was associated with better OS, whereas higher expression of CASP9, 10, 12 and 14 showed an unfavorable OS in all GC patients. Moreover, CASP1 to 8 were all associated with favorable OS in intestinal type and diffuse type classified by Lauren classification. Therefore, the results of the present study suggested that the CASP family may function as new prognostic indicators in GC and may be helpful in making treatment decisions.
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http://dx.doi.org/10.3892/ol.2019.10816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781674PMC
November 2019

Berzosertib (VE-822) inhibits gastric cancer cell proliferation via base excision repair system.

Cancer Manag Res 2019 13;11:8391-8405. Epub 2019 Sep 13.

Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.

Background: Current investigations suggest that the Base Excision Repair (BER) system may change DNA repair capacity and affect clinical gastric cancer progression such as overall survival. However, the prognostic value of BER system members in gastric cancer remains unclear.

Methods: We explored the prognostic correlation between 7 individual BER genes, including uracil-DNA glycosylase (UNG), Single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1), Methyl-CpG binding domain 4 (MBD4), thymine DNA glycosylase (TDG), 8-oxoguanine DNA glycosylase (OGG1), MutY DNA glycosylase (MUTYH) and Nei like DNA glycosylase 1 (NEIL1), expression and overall survival (OS) in different clinical data, such as Lauren classification, pathological stages, human epidermal growth factor receptor-2 (HER2) expression status, treatment strategy, gender and differentiation degree in gastric cancer patients, using Kaplan-Meier plotter (KM plotter) online database. Based on the bioinformatics analysis, we utilized Berzosertib (VE-822) to inhibit DNA damage repair in cancer cells compared to solvent control group via real-time cellular analysis (RTCA), flow cytometry, colony formation and migration assay. Finally, we utilized reverse transcription-polymerase chain reaction (RT-PCR) to confirm the expression of BER members between normal and two gastric cancer cells or solvent and VE-822 treated groups.

Results: Our work revealed that high UNG mRNA expression was correlated with high overall survival probability; however, high SMUG1, MBD4, TDG, OGG1, MUTYH and NEIL1 mRNA expression showed relatively low overall survival probability in all GC patients. Additionally, UNG was associated with high overall survival probability in intestinal and diffuse types, but SMUG1 and NEIL1 showed opposite results. Further, VE-822 pharmacological experiment suggested that inhibition of DNA damage repair suppressed gastric cancer cells' proliferation and migration ability via inducing apoptosis. Further, real-time polymerase chain reaction results proposed the inhibition of gastric cancer cells by VE-822 may be through UNG, MUTYH and OGG-1 of BER system.

Conclusion: We comprehensively analyze the prognostic value of the BER system (UNG, SMUG1, MBD4, TDG, OGG1, MUTYH and NEIL1) based on bioinformatics analysis and experimental confirmation. BER members are associated with distinctive prognostic significance and maybe new valuable prognostic indicators in gastric cancer.
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http://dx.doi.org/10.2147/CMAR.S217375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750847PMC
September 2019

Altered orbitofrontal sulcogyral patterns in gambling disorder: a multicenter study.

Transl Psychiatry 2019 08 5;9(1):186. Epub 2019 Aug 5.

Lyon Neuroscience Research Center - INSERM U1028 - CNRS UMR5292, PSYR2 Team, University of Lyon, Lyon, France.

Gambling disorder is a serious psychiatric condition characterized by decision-making and reward processing impairments that are associated with dysfunctional brain activity in the orbitofrontal cortex (OFC). However, it remains unclear whether OFC functional abnormalities in gambling disorder are accompanied by structural abnormalities. We addressed this question by examining the organization of sulci and gyri in the OFC. This organization is in place very early and stable across life, such that OFC sulcogyral patterns (classified into Types I, II, and III) can be regarded as potential pre-morbid markers of pathological conditions. We gathered structural brain data from nine existing studies, reaching a total of 165 individuals with gambling disorder and 159 healthy controls. Our results, supported by both frequentist and Bayesian statistics, show that the distribution of OFC sulcogyral patterns is skewed in individuals with gambling disorder, with an increased prevalence of Type II pattern compared with healthy controls. Examination of gambling severity did not reveal any significant relationship between OFC sulcogyral patterns and disease severity. Altogether, our results provide evidence for a skewed distribution of OFC sulcogyral patterns in gambling disorder and suggest that pattern Type II might represent a pre-morbid structural brain marker of the disease. It will be important to investigate more closely the functional implications of these structural abnormalities in future work.
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http://dx.doi.org/10.1038/s41398-019-0520-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683128PMC
August 2019

TiO nanopillar arrays coated with gelatin film for efficient capture and undamaged release of circulating tumor cells.

Nanotechnology 2019 Aug 9;30(33):335101. Epub 2019 Apr 9.

Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, Hubei, 430072, People's Republic of China.

Circulating tumor cells (CTCs) are important for the detection and treatment of cancer. Nevertheless, a low density of circulating tumor cells makes the capture and release of CTCs an obstacle. In this work, TiO nanopillar arrays coated with gelatin film were synthesized for efficient capture and undamaged release of circulating tumor cells. The scanning electron microscope and atomic force microscope images demonstrate that the substrate has a certain roughness. The interaction between the cell membrane and the nanostructure substrate contributes to the efficient capture of CTC (capture efficiency up to 94.98%). The gelatin layer has excellent biocompatibility and can be rapidly digested by matrix metalloproteinase (MMP9), which realizes the non-destructive release of CTCs (0.1 mg ml, 5 min, nearly 100% release efficiency, activity 100%). Therefore, by our strategy, the CTCs can be efficiently captured and released undamaged, which is important for subsequent analysis.
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http://dx.doi.org/10.1088/1361-6528/ab176cDOI Listing
August 2019

lncRNA CASC9 positively regulates CHK1 to promote breast cancer cell proliferation and survival through sponging the miR‑195/497 cluster.

Int J Oncol 2019 May 28;54(5):1665-1675. Epub 2019 Feb 28.

Specialized Medical Service Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.

Accumulating evidence has demonstrated that long non‑coding RNAs (lncRNAs) play important roles in the pathogenesis and development of diverse types of human disorders. Cancer susceptibility candidate 9 (CASC9), a gene encoding a lncRNA, has frequently been reported to be dysregulated and has been implicated in multiple types of human malignancies. However, the biological role of lncRNA CASC9 in breast cancer (BC) remains largely unknown. The present study aimed to investigate the role of lncRNA CASC9 in BC and to elucidate the potential molecular mechanisms involved. In the present study, lncRNA CASC9 was found to be significantly upregulated in both BC tissues and cell lines. Furthermore, functional analyses revealed that lncRNA CASC9 accelerated BC cell proliferation, promoted cell cycle progression and suppressed cell apoptosis. Moreover, mechanical experiments demonstrated that lncRNA CASC9 positively regulated checkpoint kinase 1 (CHK1) by competitively binding to the miR‑195/497 cluster in BC cells. Additionally, the knockdown of lncRNA CASC9 was observed to suppress breast tumor growth in vivo. Taken together, the results of this study indicate that lncRNA CASC9 plays an oncogenic role in BC through sponging the miR‑195/497 cluster, and that lncRNA CASC9 may be used as a novel therapeutic target and as a potential diagnostic marker for BC.
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http://dx.doi.org/10.3892/ijo.2019.4734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438439PMC
May 2019

Accurate prediction of protein-lncRNA interactions by diffusion and HeteSim features across heterogeneous network.

BMC Bioinformatics 2018 Oct 11;19(1):370. Epub 2018 Oct 11.

Lab of Information Management, Changzhou University, Jiangsu, 213164, China.

Background: Identifying the interactions between proteins and long non-coding RNAs (lncRNAs) is of great importance to decipher the functional mechanisms of lncRNAs. However, current experimental techniques for detection of lncRNA-protein interactions are limited and inefficient. Many methods have been proposed to predict protein-lncRNA interactions, but few studies make use of the topological information of heterogenous biological networks associated with the lncRNAs.

Results: In this work, we propose a novel approach, PLIPCOM, using two groups of network features to detect protein-lncRNA interactions. In particular, diffusion features and HeteSim features are extracted from protein-lncRNA heterogenous network, and then combined to build the prediction model using the Gradient Tree Boosting (GTB) algorithm. Our study highlights that the topological features of the heterogeneous network are crucial for predicting protein-lncRNA interactions. The cross-validation experiments on the benchmark dataset show that PLIPCOM method substantially outperformed previous state-of-the-art approaches in predicting protein-lncRNA interactions. We also prove the robustness of the proposed method on three unbalanced data sets. Moreover, our case studies demonstrate that our method is effective and reliable in predicting the interactions between lncRNAs and proteins.

Availability: The source code and supporting files are publicly available at: http://denglab.org/PLIPCOM/ .
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http://dx.doi.org/10.1186/s12859-018-2390-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182872PMC
October 2018

A valve-based microfluidic device for on-chip single cell treatments.

Electrophoresis 2019 03 9;40(6):961-968. Epub 2018 Sep 9.

School of Physics and Technology, Wuhan University, Wuhan, P. R. China.

Assays toward single-cell analysis have attracted the attention in biological and biomedical researches to reveal cellular mechanisms as well as heterogeneity. Yet nowadays microfluidic devices for single-cell analysis have several drawbacks: some would cause cell damage due to the hydraulic forces directly acting on cells, while others could not implement biological assays since they could not immobilize cells while manipulating the reagents at the same time. In this work, we presented a two-layer pneumatic valve-based platform to implement cell immobilization and treatment on-chip simultaneously, and cells after treatment could be collected non-destructively for further analysis. Target cells could be encapsulated in sodium alginate droplets which solidified into hydrogel when reacted with Ca . The size of hydrogel beads could be precisely controlled by modulating flow rates of continuous/disperse phases. While regulating fluid resistance between the main channel and passages by the integrated pneumatic valves, on-chip capture and release of hydrogel beads was implemented. As a proof of concept for on-chip single-cell treatments, we showed cellular live/dead staining based on our devices. This method would have potential in single cell manipulation for biochemical cellular assays.
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http://dx.doi.org/10.1002/elps.201800213DOI Listing
March 2019

Highly sensitive and rapid isolation of fetal nucleated red blood cells with microbead-based selective sedimentation for non-invasive prenatal diagnostics.

Nanotechnology 2018 Oct 8;29(43):434001. Epub 2018 Aug 8.

Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, People's Republic of China.

Non-invasive prenatal diagnostics (NIPD) has been an emerging field for prenatal diagnosis research. Carrying the whole genome coding of the fetus, fetal nucleated red blood cells (FNRBCs) have been pursued as a surrogate biomarker traveling around in maternal blood. Here, by combining a unique microbead-based centrifugal separation and enzymatic release, we demonstrated a novel method for FNRBC isolation from the blood samples. First, the gelatin-coated silica microbeads were modified with FNRBC-specific antibody (anti-CD147) to capture the target cells in the blood samples. Then, the density difference between microbead-bound FNRBCs and normal blood cells enables the purification of FNRBCs via an improved high-density percoll-based separation. The non-invasive release of FNRBCs can then be achieved by enzymatically degrading the gelatin film on the surface of the microbeads, allowing a gentle release of the captured target cells with as high as 84% efficiency and ∼80% purity. We further applied it to isolate fetal cells from maternal peripheral blood. The released cells were analyzed by real-time polymerase chain reaction to verify their fetal origin and fluorescent in situ hybridization to detect fetal chromosome disorders. This straightforward and reliable alternative platform for FNRBC detection may have the potential for realizing facile NIPD.
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http://dx.doi.org/10.1088/1361-6528/aad8c4DOI Listing
October 2018

Ontological function annotation of long non-coding RNAs through hierarchical multi-label classification.

Bioinformatics 2018 05;34(10):1750-1757

School of Software, Central South University, Changsha 410075, China.

Motivation: Long non-coding RNAs (lncRNAs) are an enormous collection of functional non-coding RNAs. Over the past decades, a large number of novel lncRNA genes have been identified. However, most of the lncRNAs remain function uncharacterized at present. Computational approaches provide a new insight to understand the potential functional implications of lncRNAs.

Results: Considering that each lncRNA may have multiple functions and a function may be further specialized into sub-functions, here we describe NeuraNetL2GO, a computational ontological function prediction approach for lncRNAs using hierarchical multi-label classification strategy based on multiple neural networks. The neural networks are incrementally trained level by level, each performing the prediction of gene ontology (GO) terms belonging to a given level. In NeuraNetL2GO, we use topological features of the lncRNA similarity network as the input of the neural networks and employ the output results to annotate the lncRNAs. We show that NeuraNetL2GO achieves the best performance and the overall advantage in maximum F-measure and coverage on the manually annotated lncRNA2GO-55 dataset compared to other state-of-the-art methods.

Availability And Implementation: The source code and data are available at http://denglab.org/NeuraNetL2GO/.

Contact: [email protected]

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btx833DOI Listing
May 2018

Computational identification of binding energy hot spots in protein-RNA complexes using an ensemble approach.

Bioinformatics 2018 05;34(9):1473-1480

School of Software, Central South University, Changsha 410075, China.

Motivation: Identifying RNA-binding residues, especially energetically favored hot spots, can provide valuable clues for understanding the mechanisms and functional importance of protein-RNA interactions. Yet, limited availability of experimentally recognized energy hot spots in protein-RNA crystal structures leads to the difficulties in developing empirical identification approaches. Computational prediction of RNA-binding hot spot residues is still in its infant stage.

Results: Here, we describe a computational method, PrabHot (Prediction of protein-RNA binding hot spots), that can effectively detect hot spot residues on protein-RNA binding interfaces using an ensemble of conceptually different machine learning classifiers. Residue interaction network features and new solvent exposure characteristics are combined together and selected for classification with the Boruta algorithm. In particular, two new reference datasets (benchmark and independent) have been generated containing 107 hot spots from 47 known protein-RNA complex structures. In 10-fold cross-validation on the training dataset, PrabHot achieves promising performances with an AUC score of 0.86 and a sensitivity of 0.78, which are significantly better than that of the pioneer RNA-binding hot spot prediction method HotSPRing. We also demonstrate the capability of our proposed method on the independent test dataset and gain a competitive advantage as a result.

Availability And Implementation: The PrabHot webserver is freely available at http://denglab.org/PrabHot/.

Contact: [email protected]

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btx822DOI Listing
May 2018

A boosting approach for prediction of protein-RNA binding residues.

BMC Bioinformatics 2017 Dec 1;18(Suppl 13):465. Epub 2017 Dec 1.

School of Software, Central South University, No.22 Shaoshan South Road, Changsha, 410075, China.

Background: RNA binding proteins play important roles in post-transcriptional RNA processing and transcriptional regulation. Distinguishing the RNA-binding residues in proteins is crucial for understanding how protein and RNA recognize each other and function together as a complex.

Results: We propose PredRBR, an effectively computational approach to predict RNA-binding residues. PredRBR is built with gradient tree boosting and an optimal feature set selected from a large number of sequence and structure characteristics and two categories of structural neighborhood properties. In cross-validation experiments on the RBP170 data set show that PredRBR achieves an overall accuracy of 0.84, a sensitivity of 0.85, MCC of 0.55 and AUC of 0.92, which are significantly better than that of other widely used machine learning algorithms such as Support Vector Machine, Random Forest, and Adaboost. We further calculate the feature importance of different feature categories and find that structural neighborhood characteristics are critical in the recognization of RNA binding residues. Also, PredRBR yields significantly better prediction accuracy on an independent test set (RBP101) in comparison with other state-of-the-art methods.

Conclusions: The superior performance over existing RNA-binding residue prediction methods indicates the importance of the gradient tree boosting algorithm combined with the optimal selected features.
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http://dx.doi.org/10.1186/s12859-017-1879-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5773889PMC
December 2017

Transarterial chemoembolisation for breast cancer with liver metastasis: A systematic review.

Breast 2017 Dec 12;36:25-30. Epub 2017 Sep 12.

General Surgery Department, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, 253 Industrial Avenue, Haizhu District, Guangzhou, Guangdong, 510282, People's Republic of China. Electronic address:

Background: There is limited data on the impact of transarterial chemoembolisation (TACE) on survival in patients of breast cancer with liver metastasis (BCLM).

Methods: A systematic review was conducted to assess TACE effect on BCLM patients. A search for clinical studies published since 1/1/2000 to 1/1/2017 was performed. Survival data from all studies were extracted to evaluate the efficacy of TACE, including overall survival, disease free survival and response rate. Toxic side effects data were also extracted to assess the safety of TACE.

Results: A total of 10 studies with 519 BCLM patients were identified. 78.0% patients were treated with TACE, 9.9% were treated with TACE plus systematic chemotherapy and 12.1% were treated with systematic chemotherapy alone. Pooled median overall survival of patients who received TACE ranged from 7.3 to 47.0 months, median disease free survival ranged from 2.9 to 17.0 months and response rates ranged from 7.0 to 73.5%. Pooled Grade 3 and 4 side effects (blood toxicities, liver toxicity and post-embolization syndrome) ranged from 0.0 to 17.4%.

Conclusions: TACE is one of an effective treatment for BCLM and whether a specific patient is appropriate to receive TACE depends on a multiple disciplinary team discussion.
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http://dx.doi.org/10.1016/j.breast.2017.09.001DOI Listing
December 2017

Cancer-Associated Fibroblasts Autophagy Enhances Progression of Triple-Negative Breast Cancer Cells.

Med Sci Monit 2017 Aug 12;23:3904-3912. Epub 2017 Aug 12.

Department of General Surgery, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China (mainland).

BACKGROUND Cancer-associated fibroblasts (CAFs) are key factors in malignant tumor initiation, progression, and metastasis. However, the effect of CAFs autophagy on triple-negative breast cancer (TNBC) cells is not clear. In this study, the growth effect of TNBC cells regulated by CAFs autophagy was evaluated. MATERIAL AND METHODS CAFs were obtained from invasive TNBC tumors and identified by Western blot and immunofluorescence staining assay. CAFs were co-cultured with TNBC cells, and migration and invasion were evaluated by Matrigel-coated Transwell and Transwell inserts. TNBC cells growth was detected by MTT assay, and epithelial-mesenchymal transition (EMT) regulated by CAFs was evaluated by Western blot assay. RESULTS CAFs were identified by the high expression of α-smooth muscle actin (α-SMA) protein. Autophagy-relevant Beclin 1 and LC3-II/I protein conversion levels in CAFs were higher than those in NFs (P<0.05). TNBC cells migration, invasion, and proliferation levels were significantly improved in the CAFs-conditioned medium (CAFs-CM) group, compared with the other 3 groups (P<0.05). TNBC cells vimentin and N-cadherin protein levels were upregulated and E-cadherin protein level was downregulated in the CAFs-CM group compared with the control group (P<0.05). Further study indicated b-catenin and P-GSK-3β protein levels, which are the key proteins in the Wnt/β-catenin pathway, were upregulated in the CAFs-CM group compared with the control group (P<0.05). CONCLUSIONS Our data demonstrated CAFs autophagy can enhance TNBC cell migration, invasion, and proliferation, and CAFs autophagy can induce TNBC cells to engage in the EMT process through the Wnt/β-catenin pathway.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5565237PMC
http://dx.doi.org/10.12659/msm.902870DOI Listing
August 2017

Novel maturity parameters for mature to over-mature source rocks and oils based on the distribution of phenanthrene series compounds.

Heliyon 2016 Mar 8;2(3):e00085. Epub 2016 Mar 8.

Key Laboratory of Petroleum Resources, Gansu Province/Key Laboratory of Petroleum Resources Research, Institute of Geology and Geophysics, Chinese Academy of Sciences, Lanzhou 730000, PR China.

Pyrolysis experiments of a low-mature bitumen sample originated from Cambrian was conducted in gold capsules. Abundance and distribution of phenanthrene series compounds in pyrolysis products were measured by GC-MS to investigate their changes with thermal maturity. Several maturity parameters based on the distribution of phenanthrene series compounds have been discussed. The results indicate that the distribution changes of phenanthrene series compounds are complex, and cannot be explained by individual reaction process during thermal evolution. The dealkylation cannot explain the increase of phenanthrene within the EasyRo range of 0.9% ∼ 2.1%. Adding of phenanthrene into maturity parameters based on the methylphenanthrene isomerization is unreasonable, even though MPI 1 and MPI 2 could be used to some extent. Two additional novel and an optimized maturation parameters based on the distribution of phenanthrene series compounds are proposed and their relationships to EasyRo% (x) are established: log(MPs/P) = 0.19x + 0.08 (0.9% < EasyRo% < 2.1%); log(MPs/P) = 0.64x - 0.86 (2.1% < EasyRo% < 3.4%); log(DMPs/TMPs) = 0.71x - 0.55 (0.9% < EasyRo% < 3.4%); log(MTR) = 0.84x - 0.75 (0.9% < EasyRo% < 3.4%). These significant positive correlations are strong argument for using log(MPs/P), log(DMPs/TMPs) and log(MTR) as maturity parameters, especially for mature to over-mature source rocks.
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http://dx.doi.org/10.1016/j.heliyon.2016.e00085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946077PMC
March 2016

Implementation of dynamically corrected gates on a single electron spin in diamond.

Phys Rev Lett 2014 Feb 6;112(5):050503. Epub 2014 Feb 6.

Hefei National Laboratory for Physics Sciences at Microscale and Department of Modern Physics, University of Science and Technology of China, Hefei 230026, China and Synergetic Innovation Center of Quantum Information and Quantum Physics, University of Science and Technology of China, Hefei, Anhui 230026, China.

Precise control of an open quantum system is critical to quantum information processing but is challenging due to inevitable interactions between the quantum system and the environment. We demonstrated experimentally a type of dynamically corrected gates using only bounded-strength pulses on the nitrogen-vacancy centers in diamond. The infidelity of quantum gates caused by a nuclear-spin bath is reduced from being the second order to the sixth order of the noise-to-control-field ratio, which offers greater efficiency in reducing infidelity. The quantum gates have been protected to the limit essentially set by the spin-lattice relaxation time T1. Our work marks an important step towards fault-tolerant quantum computation in realistic systems.
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http://dx.doi.org/10.1103/PhysRevLett.112.050503DOI Listing
February 2014

Observation of time-domain Rabi oscillations in the Landau-Zener regime with a single electronic spin.

Phys Rev Lett 2014 Jan 9;112(1):010503. Epub 2014 Jan 9.

Hefei National Laboratory for Physics Sciences at Microscale and Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui 230026, China and Synergetic Innovation Center of Quantum Information and Quantum Physics, University of Science and Technology of China, Hefei, Anhui 230026, China.

It is theoretically known that the quantum interference of a long sequence of Landau-Zener transitions can result in Rabi oscillations. Because of its stringent requirements, however, this phenomenon has never been experimentally observed in the time domain. Using a nitrogen-vacancy (NV) center spin in isotopically purified diamond, we observed the Rabi oscillations resulting from more than 100 Landau-Zener processes. Our results demonstrate favorable quantum controllability of NV centers, which could find applications in quantum metrology and quantum information processing.
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http://dx.doi.org/10.1103/PhysRevLett.112.010503DOI Listing
January 2014

Demonstration of motion transduction based on parametrically coupled mechanical resonators.

Phys Rev Lett 2013 May 29;110(22):227202. Epub 2013 May 29.

Hefei National Laboratory for Physics Sciences at Microscale and Department of Modern Physics, University of Science and Technology of China, Hefei 230026, China.

Universal sensing of the motion of mechanical resonators with high precision and low backaction is of paramount importance in ultraweak signal detection, which plays a fundamental role in modern physics. Here we present a universal scheme that mechanically transfers the motion of the resonator not directly measurable to the one that can be precisely measured using mechanical frequency conversion. Demonstration of the scheme at room temperature shows that both the motion imprecision and the backaction force are below the intrinsic level of the objective resonator, which agrees well with our theoretical prediction. The scheme developed here provides an effective interface between an arbitrary mechanical resonator and a high quantum efficient displacement sensor, and is expected to find extensive applications in highly demanding mechanical-based force measurements.
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http://dx.doi.org/10.1103/PhysRevLett.110.227202DOI Listing
May 2013
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