Publications by authors named "Xiaoqiang Sun"

103 Publications

Impaired global efficiency in boys with conduct disorder and high callous unemotional traits.

J Psychiatr Res 2021 Jun 29;138:560-568. Epub 2021 Apr 29.

Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center on Psychiatry and Psychology, Changsha, China; Medical Psychological Institute of Central South University, Changsha, China; National Clinical Research Center for Mental Disorders, Changsha, China. Electronic address:

Callous unemotional (CU) traits differentiate subtypes of conduct disorder (CD). It has been suggested that CU traits may be related to topographical irregularities that hinder information integration. To date, there is limited evidence of whether CU traits may be associated with abnormal brain topology. In this study, 43 CD boys with high and low CU trait (CD-HCU, CD-LCU), and 46 healthy controls (HCs) were subjected to resting-state functional magnetic resonance imaging to investigate how CU trait level and conduct problems may be reflected in topological organization. Brain functional networks were constructed and network/nodal properties, including small-world properties and network/nodal efficiency, were calculated. Topological analysis revealed that, compared with HCs, CD-HCU group were characterized by decreased small-worldness (σ), decreased global efficiency, and increased path length (λ). These variables were similar between the CD-LCU and HC groups. Self-reported CU traits in CD patients correlated negatively with global efficiency and positively with λ. Regional analysis revealed diminished nodal efficiency in the right amygdala in the CD-HCU group compared with HCs. The present results suggest that disrupted global efficiency, together with a regional abnormality affecting the amygdala, may contribute to abnormal information processing and integration in adolescents with CD and high CU traits.
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http://dx.doi.org/10.1016/j.jpsychires.2021.04.041DOI Listing
June 2021

Inferring latent temporal progression and regulatory networks from cross-sectional transcriptomic data of cancer samples.

PLoS Comput Biol 2021 Mar 5;17(3):e1008379. Epub 2021 Mar 5.

Department of Mathematics and Department of Developmental & Cell Biology, NSF-Simons Center for Multiscale Cell Fate Research, University of California Irvine, Irvine, California, United States of America.

Unraveling molecular regulatory networks underlying disease progression is critically important for understanding disease mechanisms and identifying drug targets. The existing methods for inferring gene regulatory networks (GRNs) rely mainly on time-course gene expression data. However, most available omics data from cross-sectional studies of cancer patients often lack sufficient temporal information, leading to a key challenge for GRN inference. Through quantifying the latent progression using random walks-based manifold distance, we propose a latent-temporal progression-based Bayesian method, PROB, for inferring GRNs from the cross-sectional transcriptomic data of tumor samples. The robustness of PROB to the measurement variabilities in the data is mathematically proved and numerically verified. Performance evaluation on real data indicates that PROB outperforms other methods in both pseudotime inference and GRN inference. Applications to bladder cancer and breast cancer demonstrate that our method is effective to identify key regulators of cancer progression or drug targets. The identified ACSS1 is experimentally validated to promote epithelial-to-mesenchymal transition of bladder cancer cells, and the predicted FOXM1-targets interactions are verified and are predictive of relapse in breast cancer. Our study suggests new effective ways to clinical transcriptomic data modeling for characterizing cancer progression and facilitates the translation of regulatory network-based approaches into precision medicine.
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http://dx.doi.org/10.1371/journal.pcbi.1008379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968745PMC
March 2021

Neuroanatomical changes associated with conduct disorder in boys: influence of childhood maltreatment.

Eur Child Adolesc Psychiatry 2021 Jan 4. Epub 2021 Jan 4.

Medical Psychological Center of Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Childhood maltreatment (CM) poses a serious risk to the physical, emotional and psychological well-being of children, and can advance the development of maladaptive behaviors, including conduct disorder (CD). CD involves repetitive, persistent violations of others' basic rights and societal norms. Little is known about whether and how CM influences the neural mechanisms underlying CD, and CD-characteristic neuroanatomical changes have not yet been defined in a structural magnetic resonance imaging (sMRI) study. Here, we used voxel-based morphometry (VBM) and surface-based morphometry (SBM) to investigate the influence of the CD diagnosis and CM on the brain in 96 boys diagnosed with CD (62 with CM) and 86 typically developing (TD) boys (46 with CM). The participants were 12-17 years of age. Compared to the CM- CD group, the CM+ CD group had structural gray matter (GM) alterations in the fronto-limbic regions, including the left amygdala, right posterior cingulate cortex (PCC), right putamen, right dorsolateral prefrontal cortex (dlPFC) and right anterior cingulate cortex (ACC). We also found boys with CD exhibited increased GM volume in bilateral dorsomedial prefrontal cortex (dmPFC), as well as decreased GM volume and decreased gyrification in the left superior temporal gyrus (STG) relative to TD boys. Regional GM volume correlated with aggression and conduct problem severity in the CD group, suggesting that the GM changes may contribute to increased aggression and conduct problems in boys with CD who have suffered CM. In conclusion, these results demonstrate previously unreported CM-associated distinct brain structural changes among CD-diagnosed boys.
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http://dx.doi.org/10.1007/s00787-020-01697-zDOI Listing
January 2021

Study on Visual Detection Algorithm of Sea Surface Targets Based on Improved YOLOv3.

Sensors (Basel) 2020 Dec 18;20(24). Epub 2020 Dec 18.

College of Intelligent Systems Science and Engineering, Harbin Engineering University, Harbin 150001, China.

Countries around the world have paid increasing attention to the issue of marine security, and sea target detection is a key task to ensure marine safety. Therefore, it is of great significance to propose an efficient and accurate sea-surface target detection algorithm. The anchor-setting method of the traditional YOLO v3 only uses the degree of overlap between the anchor and the ground-truth box as the standard. As a result, the information of some feature maps cannot be used, and the required accuracy of target detection is hard to achieve in a complex sea environment. Therefore, two new anchor-setting methods for the visual detection of sea targets were proposed in this paper: the average method and the select-all method. In addition, cross PANet, a feature fusion structure for cross-feature maps was developed and was used to obtain a better baseline cross YOLO v3, where different anchor-setting methods were combined with a focal loss for experimental comparison in the datasets of sea buoys and existing sea ships, SeaBuoys and SeaShips, respectively. The results showed that the method proposed in this paper could significantly improve the accuracy of YOLO v3 in detecting sea-surface targets, and the highest value of mAP in the two datasets is 98.37% and 90.58%, respectively.
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http://dx.doi.org/10.3390/s20247263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766418PMC
December 2020

Inferring microenvironmental regulation of gene expression from single-cell RNA sequencing data using scMLnet with an application to COVID-19.

Brief Bioinform 2021 03;22(2):988-1005

Zhong-Shan School of Medicine, Sun Yat-Sen University.

Inferring how gene expression in a cell is influenced by cellular microenvironment is of great importance yet challenging. In this study, we present a single-cell RNA-sequencing data based multilayer network method (scMLnet) that models not only functional intercellular communications but also intracellular gene regulatory networks (https://github.com/SunXQlab/scMLnet). scMLnet was applied to a scRNA-seq dataset of COVID-19 patients to decipher the microenvironmental regulation of expression of SARS-CoV-2 receptor ACE2 that has been reported to be correlated with inflammatory cytokines and COVID-19 severity. The predicted elevation of ACE2 by extracellular cytokines EGF, IFN-γ or TNF-α were experimentally validated in human lung cells and the related signaling pathway were verified to be significantly activated during SARS-COV-2 infection. Our study provided a new approach to uncover inter-/intra-cellular signaling mechanisms of gene expression and revealed microenvironmental regulators of ACE2 expression, which may facilitate designing anti-cytokine therapies or targeted therapies for controlling COVID-19 infection. In addition, we summarized and compared different methods of scRNA-seq based inter-/intra-cellular signaling network inference for facilitating new methodology development and applications.
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http://dx.doi.org/10.1093/bib/bbaa327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799217PMC
March 2021

Mechanism of ulinastatin in severe pancreatitis rats and its effect on CD4CD25 regulatory T Cells.

Minerva Med 2020 Dec 15. Epub 2020 Dec 15.

Emergency Department, Shandong Provincial Western Hospital, Jinan, China.

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http://dx.doi.org/10.23736/S0026-4806.20.07163-3DOI Listing
December 2020

Deconvolution of heterogeneous tumor samples using partial reference signals.

PLoS Comput Biol 2020 11 30;16(11):e1008452. Epub 2020 Nov 30.

Department of Mathematics, Shanghai Normal University, Shanghai, China.

Deconvolution of heterogeneous bulk tumor samples into distinct cellular populations is an important yet challenging problem, particularly when only partial references are available. A common approach to dealing with this problem is to deconvolve the mixed signals using available references and leverage the remaining signal as a new cell component. However, as indicated in our simulation, such an approach tends to over-estimate the proportions of known cell types and fails to detect novel cell types. Here, we propose PREDE, a partial reference-based deconvolution method using an iterative non-negative matrix factorization algorithm. Our method is verified to be effective in estimating cell proportions and expression profiles of unknown cell types based on simulated datasets at a variety of parameter settings. Applying our method to TCGA tumor samples, we found that proportions of pure cancer cells better indicate different subtypes of tumor samples. We also detected several cell types for each cancer type whose proportions successfully predicted patient survival. Our method makes a significant contribution to deconvolution of heterogeneous tumor samples and could be widely applied to varieties of high throughput bulk data. PREDE is implemented in R and is freely available from GitHub (https://xiaoqizheng.github.io/PREDE).
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http://dx.doi.org/10.1371/journal.pcbi.1008452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728196PMC
November 2020

Refractive Index Sensor Based on Double Side-Polished U-Shaped Plastic Optical Fiber.

Sensors (Basel) 2020 Sep 14;20(18). Epub 2020 Sep 14.

State Key Laboratory of Integrated Optoelectronics, College of Electronic Science & Engineering, Jilin University, Changchun 130012, China.

A U-shaped double-side polished plastic optical fiber (POF) is demonstrated as a liquid refractive index (RI) sensor. The refractive index of glycerinum solutions is identified by the intensity detection on the bending and evanescent wave loss change. Heat treatment and mechanical polishing are adopted to form the symmetrical side-polished POF probe. The processing parameters are experimentally optimized on the power transmittance. The sensitivity of 1541%/RIU (Refractive Index Unit) can be obtained with a resolution of 5.35 × 10 in the scope of 1.33-1.39. The favorable temperature characteristic is proved to offer stable RI sensing from 20 to 50 °C. This simple POF sensor has potentials in low-cost visible light intensity RI detection.
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http://dx.doi.org/10.3390/s20185253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570505PMC
September 2020

A Survey on Secure Computation Based on Homomorphic Encryption in Vehicular Ad Hoc Networks.

Sensors (Basel) 2020 Jul 30;20(15). Epub 2020 Jul 30.

Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China.

In vehicular ad hoc networks (VANETs), the security and privacy of vehicle data are core issues. In order to analyze vehicle data, they need to be computed. Encryption is a common method to guarantee the security of vehicle data in the process of data dissemination and computation. However, encrypted vehicle data cannot be analyzed easily and flexibly. Because homomorphic encryption supports computations of the ciphertext, it can completely solve this problem. In this paper, we provide a comprehensive survey of secure computation based on homomorphic encryption in VANETs. We first describe the related definitions and the current state of homomorphic encryption. Next, we present the framework, communication domains, wireless access technologies and cyber-security issues of VANETs. Then, we describe the state of the art of secure basic operations, data aggregation, data query and other data computation in VANETs. Finally, several challenges and open issues are discussed for future research.
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http://dx.doi.org/10.3390/s20154253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435932PMC
July 2020

The MAOA Gene Influences the Neural Response to Psychosocial Stress in the Human Brain.

Front Behav Neurosci 2020 15;14:65. Epub 2020 May 15.

Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China.

The stress response is regulated by many mechanisms. Monoamine oxidase A (MAOA) has been related to many mental illnesses. However, few studies have explored the relationship between MAOA and acute laboratory-induced psychosocial stress with functional magnetic resonance imaging (fMRI). In the current study, the Montreal Imaging Stress Task (MIST) and fMRI were used to investigate how MAOA influences the stress response. Increased cortisol concentrations were observed after the task; functional connectivity between the bilateral anterior hippocampus and other brain regions was reduced during stress. MAOA-H allele carriers showed greater deactivation of the right anterior hippocampus and greater cortisol response after stress than did MAOH-L allele carriers. Hippocampal deactivation may lead to disinhibition of the hypothalamic-pituitary-adrenal (HPA) axis and the initiation of stress hormone release under stress. Our results suggest that the MAOA gene regulates the stress response by influencing the right anterior hippocampus.
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http://dx.doi.org/10.3389/fnbeh.2020.00065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243356PMC
May 2020

The zero-frequency component of bulk waves in solids with randomly distributed micro-cracks.

Ultrasonics 2020 Sep 16;107:106172. Epub 2020 May 16.

State Key Laboratory of Reliability and Intelligence Electrical Equipment, Hebei University of Technology, Tianjin 300401, PR China; School of Mechanical Engineering, Hebei University of Technology, Tianjin 300401, PR China. Electronic address:

When a longitudinal wave (bulk wave) propagates in elastic solids with randomly distributed micro-cracks, the acoustic nonlinear behavior including the zero-frequency component and higher harmonics can be generated due to the clapping and slipping behavior of micro-cracks. In this paper, the analytical solution based on the bi-linear stiffness model of micro-cracks and the numerical simulation with random micro-crack modeling are implemented to investigate the behavior of the zero-frequency component. The theoretical and numerical results both show that the zero-frequency component of bulk waves can be generated by the micro-cracks, which is more sensitive than the conventional second harmonics. Meanwhile, we find that the acoustic nonlinearity parameter based on the zero-frequency component increases linearly with the crack density, the length of the micro-crack region and the fundamental frequency in the low-frequency region. Moreover, the zero-frequency component of the reflected waves is also investigated, indicating it can be used to locate the micro-crack region.
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http://dx.doi.org/10.1016/j.ultras.2020.106172DOI Listing
September 2020

Straight Long-Range Surface Plasmon Polariton Waveguide Sensor Operating at l = 850 nm.

Sensors (Basel) 2020 Apr 28;20(9). Epub 2020 Apr 28.

School of Electrical Engineering and Computer Science, Department of Physics, and Center for Research in Photonics, University of Ottawa, Ottawa, ON K1N 6N5, Canada.

A bulk refractive index sensor based on a straight long-range surface plasmon polariton (LRSPP) waveguide is theoretically designed. The waveguide sensor consists of an Au stripe that is embedded in ultraviolet sensitive polymer SU-8. The geometric parameters are optimized by finite difference eigenmode method at the optical wavelength of 850 nm. The sensitivity of 196 dB/RIU/mm can be obtained with a 1.5 μm wide, 25 nm thick Au stripe waveguide. Straight LRSPP waveguides are fabricated by a double layer lift-off process. Its optical transmission is characterized to experimentally prove the feasibility of the proposed design. This sensor has potential for the realization of a portable, low-cost refractometer.
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http://dx.doi.org/10.3390/s20092507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273216PMC
April 2020

Influence of psychosocial stress on activation in human brain regions: moderation by the 5-HTTLPR genetic locus.

Physiol Behav 2020 06 16;220:112876. Epub 2020 Mar 16.

Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China; Medical Psychological Institute of Central South University, Changsha 410011, Hunan, China; National Clinical Research Center for Mental Disorders. Electronic address:

Variants of the serotonin transporter linked polymorphic region (5-HTTLPR) of the serotonin transporter gene SLC6A4 have been related with the onset of depression, anxiety, and other mental disorders. Homozygotes for the short 5-HTTLPR variant, referred to as the SS genotype, have greater cortisol responses to experimentally induced psychosocial stress. In the current study, we used functional magnetic resonance imaging (fMRI) to compare regional brain activations across 5-HTTLPR genotypes in subjects performing the Montreal Imaging Stress Task (MIST). Subjects with an SS genotype had significant greater increases in cortisol concentrations after the task than subjects with at least one long 5-HTTLPR allele. Additionally, relative to L carriers, the SS group had greater activation in the dorsomedial prefrontal cortex(dmPFC), dorsal anterior cingulate cortex, anterior insula.
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http://dx.doi.org/10.1016/j.physbeh.2020.112876DOI Listing
June 2020

Childhood Maltreatment Experience Influences Neural Response to Psychosocial Stress in Adults: An fMRI Study.

Front Psychol 2019 14;10:2961. Epub 2020 Jan 14.

Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, China.

Background: Childhood maltreatment is a strong risk factor for the development of depression in later life. However, the neurobiological mechanisms underlying this vulnerability are not well understood. As depression has been associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and increased responsiveness to psychosocial stressors, we speculated that childhood maltreatment may lead to lasting alteration of the stress response system, thereby increasing the risk of depression. This study investigated the effects of childhood maltreatment on the stress response in healthy subjects while controlling for psychiatric condition.

Methods: Forty-eight healthy young adults (24 females) with childhood maltreatment experience and 48 healthy controls (33 females) without such experience were administered the Montreal Imaging Stress Task during functional magnetic resonance imaging. Childhood maltreatment experience was assessed using the 28-item Childhood Trauma Questionnaire (CTQ). Between-group differences in subjective stress levels, whole brain activations and cortisol levels were assessed.

Results: Relative to healthy control subjects, individuals exposed to childhood maltreatment exhibited higher subjective stress and cortisol levels. Neurofunctionally, participants with histories of childhood maltreatment displayed significantly increased activation in the dorsolateral prefrontal cortex (dlPFC), insula and precuneus, and decreased activation in ventromedial prefrontal cortex (vmPFC) relative to healthy controls during the psychosocial stress task. Activations in dlPFC and insula correlated with CTQ scores in the childhood maltreatment group.

Conclusion: The results of this study show that childhood maltreatment induces lasting changes in brain function and HPA-axis responsiveness to stress. The observed abnormal activation in the dlPFC, insula and vmPFC and enhanced cortisol response are similar to those seen in individuals with depression. This dysfunction might serve as a diathesis that embeds latent vulnerability to psychiatric disorders, and this mechanism provides evidence supporting the stress sensitization model.
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http://dx.doi.org/10.3389/fpsyg.2019.02961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971063PMC
January 2020

Compact Inner-Wall Grating Slot Microring Resonator for Label-Free Sensing.

Sensors (Basel) 2019 Nov 19;19(22). Epub 2019 Nov 19.

State Key Laboratory of Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, 2699 Qianjin Street, Changchun 130012, China.

In this paper, we present and analyze a compact inner-wall grating slot microring resonator (IG-SMRR) with the footprint of less than 13 μm × 13 μm on the silicon-on-insulator (SOI) platform for label-free sensing, which comprises a slot microring resonator (SMRR) and inner-wall grating (IG). Its detection range is significantly enhanced without the limitation of the free spectral region (FSR) owing to the combination of SMRR and IG. The IG-SMRR has an ultra-large quasi-FSR of 84.5 nm as the detection range, and enlarged factor is up to over 3 compared with the conventional SMRR. The concentration sensitivities of sodium chloride solutions and D-glucose solutions are 996.91 pm/% and 968.05 pm/%, respectively, and the corresponding refractive index (RI) sensitivities are 559.5 nm/RIU (refractive index unit) and 558.3 nm/RIU, respectively. The investigation on the combination of SMRR and IG is a valuable exploration of label-free sensing application for ultra-large detection range and ultra-high sensitivity in future.
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http://dx.doi.org/10.3390/s19225038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891492PMC
November 2019

Neuroticism modulates neural activities of posterior cingulate cortex and thalamus during psychosocial stress processing.

J Affect Disord 2020 02 4;262:223-228. Epub 2019 Nov 4.

Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China; Medical Psychological Institute of Central South University, Changsha, Hunan, China; China National Clinical Research Center on Mental Disorders (Xiangya), Changsha, Hunan, China. Electronic address:

Objective: Individuals with higher neuroticism are vulnerable to stress and are prone to develop depression, however, the neural mechanisms underlying it have not been clarified clearly.

Method: The Montreal Imaging Stress Task (MIST) was administered to 148 healthy adults during functional magnetic resonance imaging (fMRI). Whole-brain voxel-wise regression analyses were used to detect associations of neuroticism with neural activity involved in perceiving and processing psychosocial stress. In addition, two-sample t-tests were conducted between the high-neurotic and low-neurotic group in order to supplement the results found in regression analyses.

Results: Higher neuroticism scores were associated with higher activities in the posterior cingulate cortex (PCC)/precuneus and thalamus (p < 0.05, false discovery rate correction). Moreover, two sample t-tests also revealed that the high-neurotic group had higher neural stress responses in precuneus and bilateral thalamus in comparison to the low-neurotic group (p < 0.05, false discovery rate correction).

Limitations: Our study mainly recruited young adults, which may limit the generalizability of our findings.

Conclusions: Our findings highlight the crucial role of PCC/precuneus and thalamus in the association between neuroticism and stress and may provide insight into the cognitive model of depression.
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http://dx.doi.org/10.1016/j.jad.2019.11.003DOI Listing
February 2020

Differential regulatory network-based quantification and prioritization of key genes underlying cancer drug resistance based on time-course RNA-seq data.

PLoS Comput Biol 2019 11 4;15(11):e1007435. Epub 2019 Nov 4.

Department of Medical Informatics, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China; Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Chinese Ministry of Education, Guangzhou, Guangdong, China.

Drug resistance is a major cause for the failure of cancer chemotherapy or targeted therapy. However, the molecular regulatory mechanisms controlling the dynamic evolvement of drug resistance remain poorly understood. Thus, it is important to develop methods for identifying key gene regulatory mechanisms of the resistance to specific drugs. In this study, we developed a data-driven computational framework, DryNetMC, using a differential regulatory network-based modeling and characterization strategy to quantify and prioritize key genes underlying cancer drug resistance. The DryNetMC does not only infer gene regulatory networks (GRNs) via an integrated approach, but also characterizes and quantifies dynamical network properties for measuring node importance. We used time-course RNA-seq data from glioma cells treated with dbcAMP (a cAMP activator) as a realistic case to reconstruct the GRNs for sensitive and resistant cells. Based on a novel node importance index that comprehensively quantifies network topology, network entropy and expression dynamics, the top ranked genes were verified to be predictive of the drug sensitivities of different glioma cell lines, in comparison with other existing methods. The proposed method provides a quantitative approach to gain insights into the dynamic adaptation and regulatory mechanisms of cancer drug resistance and sheds light on the design of novel biomarkers or targets for predicting or overcoming drug resistance.
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http://dx.doi.org/10.1371/journal.pcbi.1007435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827891PMC
November 2019

A Polymer Asymmetric Mach-Zehnder Interferometer Sensor Model Based on Electrode Thermal Writing Waveguide Technology.

Micromachines (Basel) 2019 Sep 20;10(10). Epub 2019 Sep 20.

State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130012, China.

This paper presents a novel electrode thermal writing waveguide based on a heating-induced refractive index change mechanism. The mode condition and the electrode thermal writing parameters were optimized, and the output patterns of the optical field were obtained in a series of simulations. Moreover, the effect of various adjustments on the sensing range of the nanoimprint M-Z temperature sensor was analyzed theoretically. A refractive index asymmetry Mach-Zehnder (M-Z) waveguide sensor with a tunable refractive index for a waveguide core layer was simulated with a length difference of 946.1 µm. The optimal width and height of the invert ridge waveguide were 2 μm and 2.8 μm, respectively, while the slab thickness was 1.2 μm. The sensing accuracy was calculated to range from 2.0896 × 10 to 5.1252 × 10 in the 1.51-1.54 region. The sensing fade issue can be resolved by changing the waveguide core refractive index to 0.001 via an electrode thermal writing method. Thermal writing a single M-Z waveguide arm changes its refractive index by 0.03. The sensor's accuracy can be improved 1.5 times by the proposed method. The sensor described in this paper shows great prospects in organism temperature detection, molecular analysis, and biotechnology applications.
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http://dx.doi.org/10.3390/mi10100628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843899PMC
September 2019

Metal-printing polymer waveguide thermo-optic switches compatible with 650 and 532  nm visible signal wavelengths for plastic optical fiber systems.

Appl Opt 2019 Sep;58(25):6820-6826

In this work, thermo-optic (TO) waveguide switches for 650 and 532 nm visible wavelengths are designed and fabricated by the metal-printing technique based on poly (methyl methacrylate-glycidyl methacrylate) [P(MMA-GMA)] material. The optical characteristics and thermal stability of the P(MMA-GMA) material are analyzed. Optical transmission modes in the core waveguide for different visible wavelengths are simulated, and the thermal field distribution from the self-heating electrode structure is calculated, respectively. The structural parameters of the devices compatible with 650 and 532 nm visible wavelengths are designed optimally. For 650 and 532 nm signal wavelengths, the insertion loss of the actual TO switch fabricated is less than 3.2 dB, and the response time of the device is about 367.4 μs at 100 Hz square wave electrical signals. The driving electrical power of the device for the 650 nm signal wavelength is 15.2 mW and 14.0 mW for the 532 nm signal wavelength, respectively. The extinction ratio of the visible TO switch for 650 nm is 15.1 dB and 18.5 dB for 532 nm, respectively. The technique is suitable for realizing plastic optical fiber system applications.
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http://dx.doi.org/10.1364/AO.58.006820DOI Listing
September 2019

State-independent and -dependent structural alterations in limbic-cortical regions in patients with current and remitted depression.

J Affect Disord 2019 11 30;258:1-10. Epub 2019 Jul 30.

Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Medical Psychological Institute of Central South University, Changsha, Hunan 410011, China; China National Clinical Research Center on Mental disorders (Xiangya), Changsha, Hunan 410011, China. Electronic address:

Background: The high recurrence of major depressive disorder (MDD) may derive from underlying state-independent structural alterations.

Methods: First-episode drug-naïve currently depressed (cMDD) patients (N = 97), remitted depressed (RD) patients (N = 72), and healthy controls (HCs, N = 100) underwent structural magnetic resonance imaging (MRI). Group differences in cortical thickness (CT), surface area (SA), and local gyrification index (lGI) were analyzed in FreeSurfer.

Results: Both groups of depressed patients had significantly decreased CT, relative to HCs, in the left precentral gyrus and significantly increased lGI values in the left superior frontal gyrus (SFG) indicative of state-independent alterations. Relative to HCs, the cMDD group had decreased CT of the SFG, caudal middle frontal gyrus (MFG), posterior cingulate cortex (PCC), and lateral occipital regions as well as increased SA or lGI of the superior temporal gyrus, precuneus, and pericalcarine, whereas the RD group had increased SA or lGI of the SFG, caudal MFG, and supramarginal gyrus; these alterations appeared to be state-dependent. SA or lGI values of the fusiform gyrus, inferior temporal gyrus, and superior parietal lobule differed between the cMDD and RD groups, consistent with state-dependent alterations. Beck depression inventory scores correlated with CT or lGI values of the caudal MFG, lateral occipital cortex in depressed patients.

Limitations: The structural features of several subcortical limbic regions were not analyzed.

Conclusions: Left precentral gyrus CT and left SFG gyrification alterations may represent state-independent alterations in MDD.
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http://dx.doi.org/10.1016/j.jad.2019.07.065DOI Listing
November 2019

Single-cell transcriptome-based multilayer network biomarker for predicting prognosis and therapeutic response of gliomas.

Brief Bioinform 2020 05;21(3):1080-1097

School of Mathematics, Sun Yat-Sen University, Guangzhou, China.

Occurrence and development of cancers are governed by complex networks of interacting intercellular and intracellular signals. The technology of single-cell RNA sequencing (scRNA-seq) provides an unprecedented opportunity for dissecting the interplay between the cancer cells and the associated microenvironment. Here we combined scRNA-seq data with clinical bulk gene expression data to develop a computational pipeline for identifying the prognostic and predictive signature that connects cancer cells and microenvironmental cells. The pipeline was applied to glioma scRNA-seq data and revealed a tumor-associated microglia/macrophage-mediated EGFR/ERBB2 feedback-crosstalk signaling module, which was defined as a multilayer network biomarker (MNB) to predict survival outcome and therapeutic response of glioma patients. We used publicly available clinical data sets from large cohorts of glioma patients to examine the prognostic significance and predictive accuracy of the MNB, which outperformed conventional gene biomarkers and other methods. Additionally, the MNB was found to be predictive of the sensitivity or resistance of glioma patients to molecularly targeted therapeutics. Moreover, the MNB was an independent and the strongest prognostic factor when adjusted for clinicopathologic risk factors and other existing gene signatures. The robustness of the MNB was further tested on additional data sets. Our study presents a promising scRNA-seq transcriptome-based multilayer network approach to elucidate the interactions between tumor cell and tumor-associated microenvironment and to identify prognostic and predictive signatures of cancer patients. The proposed MNB method may facilitate the design of more effective biomarkers for predicting prognosis and therapeutic resistance of cancer patients.
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http://dx.doi.org/10.1093/bib/bbz040DOI Listing
May 2020

Effects of BDNF Val66Met polymorphisms on brain structures and behaviors in adolescents with conduct disorder.

Eur Child Adolesc Psychiatry 2020 Apr 1;29(4):479-488. Epub 2019 Jul 1.

Center of Functional Neuroimaging, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Accumulating evidence suggests that neural abnormalities in conduct disorder (CD) may be subject to genetic influences, but few imaging studies have taken genetic variants into consideration. The Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) has emerged as a high-interest genetic variant due to its importance in cortical maturation, and several studies have implicated its involvement in neurodevelopmental disorders. Thus, it is unclear how this polymorphism may influence brain anatomy and aberrant behaviors in CD. A total of 65 male adolescents with CD and 69 gender-, IQ- and socioeconomic status-matched healthy controls (HCs) (age range 13-17 years) were enrolled in this study. Analyses of variance (ANOVAs) were used to assess the main effects of CD diagnosis, BDNF genotype, and diagnosis-genotype interactions on brain anatomy and behaviors. We detected a significant main effect of BDNF genotype on temporal gyrification and antisocial behaviors, but not on CD symptoms. Diagnosis-genotype interactive effects were found for cortical thickness of the superior temporal and adjacent areas. These results suggest that the BDNF Val66Met polymorphism may exert its influence both on neural alterations and delinquent behaviors in CD patients. This initial evidence highlights the importance of elucidating potentially different pathways between BDNF genotype and cortical alterations or delinquent behaviors in CD patients.
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http://dx.doi.org/10.1007/s00787-019-01363-zDOI Listing
April 2020

Multicellular gene network analysis identifies a macrophage-related gene signature predictive of therapeutic response and prognosis of gliomas.

J Transl Med 2019 05 16;17(1):159. Epub 2019 May 16.

Faculty of Health Sciences, University of Macau, Taipa, Macau, China.

Background: The tumor-associated microenvironment plays important roles in tumor progression and drug resistance. However, systematic investigations of macrophage-tumor cell interactions to identify novel macrophage-related gene signatures in gliomas for predicting patient prognoses and responses to targeted therapies are lacking.

Methods: We developed a multicellular gene network approach to investigating the prognostic role of macrophage-tumor cell interactions in tumor progression and drug resistance in gliomas. Multicellular gene networks connecting macrophages and tumor cells were constructed from re-grouped drug-sensitive and drug-resistant samples of RNA-seq data in mice gliomas treated with BLZ945 (a CSF1R inhibitor). Subsequently, a differential network-based COX regression model was built to identify the risk signature using a cohort of 310 glioma samples from the Chinese Glioma Genome Atlas database. A large independent validation set of 690 glioma samples from The Cancer Genome Atlas database was used to test the prognostic significance and accuracy of the gene signature in predicting prognosis and targeted therapeutic response of glioma patients.

Results: A macrophage-related gene signature was developed consisting of twelve genes (ANPEP, DPP4, PRRG1, GPNMB, TMEM26, PXDN, CDH6, SCN3A, SEMA6B, CCDC37, FANCA, NETO2), which was tested in the independent validation set to examine its prognostic significance and accuracy. The generation of 1000 random gene signatures by a bootstrapping scheme justified the non-random nature of the macrophage-related gene signature. Moreover, the discovered gene signature was verified to be predictive of the sensitivity or resistance of glioma patients to molecularly targeted therapeutics and outperformed other existing gene signatures. Additionally, the macrophage-related gene signature was an independent and the strongest prognostic factor when adjusted for clinicopathologic risk factors and other existing gene signatures.

Conclusion: The multicellular gene network approach developed herein indicates profound roles of the macrophage-mediated tumor microenvironment in the progression and drug resistance of gliomas. The identified macrophage-related gene signature has good prognostic value for predicting resistance to targeted therapeutics and survival of glioma patients, implying that combining current targeted therapies with new macrophage-targeted therapy may be beneficial for the long-term treatment outcomes of glioma patients.
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http://dx.doi.org/10.1186/s12967-019-1908-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524242PMC
May 2019

Multiscale modeling reveals angiogenesis-induced drug resistance in brain tumors and predicts a synergistic drug combination targeting EGFR and VEGFR pathways.

BMC Bioinformatics 2019 May 1;20(Suppl 7):203. Epub 2019 May 1.

Zhong-shan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.

Background: Experimental studies have demonstrated that both the extracellular vasculature or microenvironment and intracellular molecular network (e.g., epidermal growth factor receptor (EGFR) signaling pathway) are important for brain tumor growth. Additionally, some drugs have been developed to inhibit EGFR signaling pathways. However, how angiogenesis affects the response of tumor cells to drug treatment has rarely been mechanistically studied. Therefore, a multiscale model is required to investigate such complex biological systems that contain interactions and feedback among multiple levels.

Results: In this study, we developed a single cell-based multiscale spatiotemporal model to simulate vascular tumor growth and the drug response based on the vascular endothelial growth factor receptor (VEGFR) signaling pathway, the EGFR signaling pathway and the cell cycle as well as several microenvironmental factors that determine cell fate switches in a temporal and spatial context. By incorporating the EGFRI treatment effect, the model showed an interesting phenomenon in which the survival rate of tumor cells decreased in the early stage but rebounded in a later stage, revealing the emergence of drug resistance. Moreover, we revealed the critical role of angiogenesis in acquired drug resistance, since inhibiting blood vessel growth using a VEGFR inhibitor prevented the recovery of the survival rate of tumor cells in the later stage. We further investigated the optimal timing of combining VEGFR inhibition with EGFR inhibition and predicted that the drug combination targeting both the EGFR pathway and VEGFR pathway has a synergistic effect. The experimental data validated the prediction of drug synergy, confirming the effectiveness of our model. In addition, the combination of EGFR and VEGFR genes showed clinical relevance in glioma patients.

Conclusions: The developed multiscale model revealed angiogenesis-induced drug resistance mechanisms of brain tumors to EGFRI treatment and predicted a synergistic drug combination targeting both EGFR and VEGFR pathways with optimal combination timing. This study explored the mechanistic and functional mechanisms of the angiogenesis underlying tumor growth and drug resistance, which advances our understanding of novel mechanisms of drug resistance and provides implications for designing more effective cancer therapies.
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http://dx.doi.org/10.1186/s12859-019-2737-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509865PMC
May 2019

Fluorinated photopolymer cascaded MMI-based integrated optical waveguide switching matrix with encoding functions.

Opt Express 2019 Apr;27(9):12883-12898

In this work, thermo-optic tunable 4 × 4 cascaded multimode interference based integrated optical waveguide switching matrices are designed and fabricated using photopolymer lightwave circuits. The materials of the waveguide core and cladding are fluorinated epoxy-terminated copolycarbonate and polymethylmethacrylate, respectively. The driving power that controls matrices for binary encoding of different optical switching states are simulated and analyzed. The measured insertion loss of the actual chip is < 7.1 dB and the maximum crosstalk in adjacent channels is <-30 dB. The switching time is approximately 220 μs and the extinction ratio is obtained as 21.5 dB. This flexible encoding technique can be applied for achieving optical code-division multiple-access network coders.
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http://dx.doi.org/10.1364/OE.27.012883DOI Listing
April 2019

Ultra-sensitive polymeric waveguide temperature sensor based on asymmetric Mach-Zehnder interferometer.

Appl Opt 2019 Feb;58(5):1276-1280

We proposed and designed an ultra-sensitive polymeric waveguide temperature sensor based on an asymmetric Mach-Zehnder interferometer that has different widths in the two interferometer arms. A polymer with a larger thermo-optic coefficient (TOC) was employed to enhance the sensitivity of the waveguide temperature sensor. The influence of the width difference between the two arms and the cladding materials with different TOCs on the sensitivity of the sensor was studied and experimentally demonstrated. The devices were fabricated by using the standard photolithography and simple all-wet etching process. When the cladding material Norland optical adhesive 73 (NOA 73) and the width difference of 6.5 μm were selected, the sensitivity of the waveguide temperature sensor was measured to be 30.8 nm/°C. Moreover, the minimum temperature resolution was about 0.97×10°. The proposed sensor has the distinct advantages of high sensitivity, high resolution, easy fabrication, low cost, and biological compatibility, which make it have potential applications in temperature detection of organisms, molecular analysis, and biotechnology.
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http://dx.doi.org/10.1364/AO.58.001276DOI Listing
February 2019

Topologically state-independent and dependent functional connectivity patterns in current and remitted depression.

J Affect Disord 2019 05 5;250:178-185. Epub 2019 Mar 5.

Medical Psychological Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China; Medical Psychological Institute of Central South University, Changsha, Hunan, PR China; China National Clinical Research Center on Mental Disorders (Xiangya), Changsha, Hunan, PR China. Electronic address:

Objective: Identification of state-independent and -dependent neural biomarkers may provide insight into the pathophysiology and effective treatment of major depressive disorder (MDD), therefore we aimed to investigate the state-independent and -dependent topological alterations of MDD.

Method: Brain resting-state functional magnetic resonance imaging (fMRI) data were acquired from 59 patients with unmedicated first episode current MDD (cMDD), 48 patients with remitted MDD (rMDD) and 60 demographically matched healthy controls (HCs). Using graph theory, we systematically studied the topological organization of their whole-brain functional networks at the global and nodal level.

Results: At a global level, both patient groups showed decreased normalized clustering coefficient in relative to HCs. On a nodal level, both patient groups showed decreased nodal centrality, predominantly in cortex-mood-regulation brain regions including the dorsolateral prefrontal cortex, posterior parietal cortex and posterior cingulate cortex. By comparison to cMDD patients, rMDD group had a higher nodal centrality in right parahippocampal gyrus.

Limitations: The present study, an exploratory analysis, may require further confirmation with task-based and experimental studies.

Conclusions: Deficits in the topological organization of the whole brain and cortex-mood-regulation brain regions in both rMDD and cMDD represent state-independent biomarkers.
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http://dx.doi.org/10.1016/j.jad.2019.03.030DOI Listing
May 2019

State-Related Alterations of Spontaneous Neural Activity in Current and Remitted Depression Revealed by Resting-State fMRI.

Front Psychol 2019 11;10:245. Epub 2019 Feb 11.

Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China.

Although efforts have been made to identify neurobiological characteristic of major depressive disorder (MDD) in recent years, trait- and state-related biological characteristics of MDD still remains unclear. Using functional magnetic resonance imaging (fMRI), the aim of this study was to explore whether altered spontaneous neural activities in MDD are trait- or state- related. Resting-state fMRI data were analyzed for 72 current MDD (cMDD) patients (first-episode, medication-naïve), 49 remitted MDD (rMDD) patients, and 78 age- and sex- matched healthy control (HC) subjects. The values of amplitude of low-frequency fluctuation (ALFF) were compared between groups. Compared with the cMDD group, the rMDD group had increased ALFF values in the left middle occipital gyrus, left middle temporal gyrus and right cerebellum anterior lobe. Besides, compared with the HC group, the cMDD group had decreased ALFF values in the left middle occipital gyrus. Further analysis explored that the mean ALFF values in the left middle occipital gyrus, left middle temporal gyrus and right cerebellum anterior lobe were correlated positively with BDI scores in rMDD patients. Abnormal activity in the left middle occipital gyrus, left middle temporal gyrus and right cerebellum anterior lobe may be state-specific in current (first-episode, medication-naïve) and remitted (medication-naïve) depression patients. Furthermore, the state-related compensatory effect was found in these brain areas.
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http://dx.doi.org/10.3389/fpsyg.2019.00245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378291PMC
February 2019

Regional Homogeneity Abnormalities in Early-Onset and Adolescent-Onset Conduct Disorder in Boys: A Resting-State fMRI Study.

Front Hum Neurosci 2019 7;13:26. Epub 2019 Feb 7.

Department of Radiology, Second Xiangya Hospital, Central South University, Changsha, China.

: Developmental taxonomic theory posits that formation of early-onset conduct disorder (EO-CD), is considered to have a neurodevelopmental etiology and have more severe psychosocial and neuropsychological dysfunction than adolescent-onset CD (AO-CD), which is thought to stem largely from social mimicry of deviant peers. The purpose of the current study was to investigate whether regional homogeneity (ReHo), denoting the spontaneous brain activity, supports developmental taxonomic theory in a resting state (rs). : Rs-functional magnetic resonance imaging (fMRI) examinations were administered to 36 EO-CD patients, 32 AO-CD patients, and 30 healthy controls (HCs). All participants were male adolescents, aged between 12 and 17 years old. A one-way analysis of covariance (ANCOVA), with age and IQ as covariates, was performed to identify regions with significant group differences in ReHo values, followed by a analyses. : Compared with the AO-CD groups, EO-CD had higher ReHo values in the right middle/inferior frontal gyrus. Compared with the HCs, the EO-CD group exhibited lower ReHo values in the left precuneus, left middle occipital gyrus, left cerebellum posterior lobe and the right inferior parietal lobule, as well as higher ReHo values in the right middle frontal gyrus, left insula/inferior frontal gyrus, right postcentral gyrus, and the left anterior cingulate gyrus. Compared with the HCs, the AO-CD group showed lower ReHo values in the bilateral precuneus, left cerebellum posterior lobe, and the right inferior parietal lobule. : Significant differences in ReHo were observed between the EO-CD and AO-CD groups, implying distinct neuropathological mechanisms of the two CD subtypes, consistent with developmental taxonomic theory. CD-associated abnormalities in ReHo may be related to high-order cognitive and low-level perceptual system impairments in CD.
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http://dx.doi.org/10.3389/fnhum.2019.00026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374554PMC
February 2019