Lin Chen

Taiyuan University of Technology, Yangkü, Shanxi Sheng, China

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Publications (126)434.27 Total impact

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    ABSTRACT: The histone methylation on lysine residues is one of the most studied post-translational modifications, and its aberrant states have been associated with many human diseases. In 2012, Kruidenier et al. reported GSK-J1 as a selective Jumonji H3K27 demethylase (JMJD3 and UTX) inhibitor. However, there is limited information on the structure–activity relationship of this series of compounds. Moreover, there are few scaffolds reported as chelating groups for Fe(II) ion in Jumonji demethylase inhibitors development. To further elaborate the structure–activity relationship of selective JMJD3 inhibitors and to explore the novel chelating groups for Fe(II) ion, we initialized a medicinal chemistry modification based on the GSK-J1 structure. Finally, we found that several compounds bearing different chelating groups showed similar activities with respect to GSK-J1 and excellent metabolic stability in liver microsomes. The ethyl ester prodrugs of these inhibitors also showed a better activity than GSK-J4 for inhibition of TNF-α production in LPS-stimulated murine macrophage cell line Raw 264.7 cells. Taking together, the current study not only discovered alternative potent JMJD3 inhibitors, but also can benefit other researchers to design new series of Jumonji demethylase inhibitors based on the identified chelating groups.
    No preview · Article · Jan 2016 · Bioorganic & medicinal chemistry letters
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    ABSTRACT: Rhodamine B, a familiar organic dye, was embedded in mesoporous silica (MCM-41) which had been modified by (3-Aminopropyl) triethoxysilane (APTES) through chemical bonding method. The materials were investigated by small angle X-ray diffraction (XRD), Transmission electron microcopy (TEM), Fourier transform infrared spectrometry (FT-IR), and Photoluminescence spectroscopy (PL). The structure of the composites was characterized by XRD, which reveals that the mesoporous structure is maintained and the functional groups have been introduced into the mesostructure. The TEM photograph of the sample future shows that the ordered mesoporous structure is maintained after grafting. The FT-IR spectra improve that RhB has been successfully introduced into the mesoporous silica (MCM-41). The PL spectra of the product indicate that the emission spectrum shift to lower wavelength after grafting.
    No preview · Article · Jan 2016 · Synthesis and Reactivity in Inorganic Metal-Organic and Nano-Metal Chemistry
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    ABSTRACT: Thymic epithelial cells (TECs) form a 3-dimentional network supporting thymocyte development and maturation. Besides epithelium and thymocytes, heterogeneous fibroblasts are essential components in maintaining thymic microenvironments. However, thymic fibroblast characteristics, development and function remain to be determined. We herein found that thymic non-hematopoietic CD45- FSP1+ cells represent a unique Fibroblast specific protein 1 (FSP1)- fibroblast-derived cell subset. Deletion of these cells in FSP1-TK transgenic mice caused thymus atrophy due to the loss of TECs, especially mature medullary TECs (MHCIIhigh, CD80+ and Aire+). In a cyclophosphamide-induced thymus injury and regeneration model, lack of non-hematopoietic CD45- FSP1+ fibroblast subpopulation significantly delayed thymus regeneration. In fact, thymic FSP1+ fibroblasts released more IL-6, FGF7 and FSP1 in the culture medium than their FSP1- counterparts. Further experiments showed that the FSP1 protein could directly enhance the proliferation and maturation of TECs in the in vitro culture systems. FSP1 knockout mice had significantly smaller thymus size and less TECs than their control. Collectively, our studies reveal that thymic CD45- FSP1+ cells are a subpopulation of fibroblasts, which is crucial for the maintenance and regeneration of TECs especially medullary TECs through providing IL-6, FGF7 and FSP1.
    Full-text · Article · Oct 2015 · Scientific Reports
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    Lixia He · Ke Zhou · Tiangang Zhou · Sheng He · Lin Chen
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    ABSTRACT: What is a number? The number sense hypothesis suggests that numerosity is "a primary visual property" like color, contrast, or orientation. However, exactly what attribute of a stimulus is the primary visual property and determines numbers in the number sense? To verify the invariant nature of numerosity perception, we manipulated the numbers of items connected/enclosed in arbitrary and irregular forms while controlling for low-level features (e.g., orientation, color, and size). Subjects performed discrimination, estimation, and equality judgment tasks in a wide range of presentation durations and across small and large numbers. Results consistently show that connecting/enclosing items led to robust numerosity underestimation, with the extent of underestimation increasing monotonically with the number of connected/enclosed items. In contrast, grouping based on color similarity had no effect on numerosity judgment. We propose that numbers or the primitive units counted in numerosity perception are influenced by topological invariants, such as connectivity and the inside/outside relationship. Beyond the behavioral measures, neural tuning curves to numerosity in the intraparietal sulcus were obtained using functional MRI adaptation, and the tuning curves showed that numbers represented in the intraparietal sulcus were strongly influenced by topology.
    Preview · Article · Sep 2015 · Proceedings of the National Academy of Sciences
  • Jing Li · Wei Zhang · Lin Chen · Jun Liang · Kuangfei Lin
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    ABSTRACT: BDE209 and Pb are ubiquitous contaminants at e-waste recycling sites (EWRSs). This study aimed to determine acute and sub-acute toxicity to earthworm Eisenia fetida induced by BDE209 and Pb in natural soil. Results demonstrated that the inhibition of Pb on growth and reproduction of earthworms followed a dose-dependent pattern. Earthworms exposed to 100 mg kg(-1) of BDE209 displayed avoidance responses, while the soil indicated a more obvious decline of habitat function with the increase of Pb level. Comet assay suggested that increasing concentrations of Pb exposure resulted in a gradual increase in the tail length and olive tail moment, which meant that the degree of DNA damage was promoted. BDE209 addition could reduce the damage; therefore the joint effects of both chemicals showed antagonistic. These results revealed that joint exposure (BDE209-Pb) could elicit pronounced biochemical and physiological responses in earthworms, and the DNA damage might be potential molecular biomarker of the two pollutants.
    No preview · Article · Sep 2015 · Environmental Pollution
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    ABSTRACT: Since 2013, avian influenza A(H7N9) viruses have diversified into multiple lineages by dynamically reassorting with other viruses, especially H9N2, in Chinese poultry. Despite concerns about the pandemic threat posed by H7N9 viruses, little is known about the biological properties of H7N9 viruses that may recruit internal genes from genetically distinct H9N2 viruses circulating among wild birds. Here, we generated 63 H7N9 reassortants derived from an avian H7N9 and a wild-bird-origin H9N2 virus. Compared with the wild-type parent, 25/63 reassortants had increased pathogenicity in mice. A reassortant containing PB1 of the H9N2 virus was highly lethal to mice and chickens but was not transmissible to guinea pigs by airborne routes; however, three substitutions associated with adaptation to mammals conferred airborne transmission to the virus. The emergence of the H7N9-pandemic reassortant virus highlights that continuous monitoring of H7N9 viruses is needed, especially at the domestic poultry/wild bird interface.
    Preview · Article · Sep 2015 · Cell Reports
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    ABSTRACT: Diurnal animals are a better model for seasonal affective disorder (SAD) than nocturnal ones. Previous work with diurnal rodents demonstrated that short photoperiod conditions brought about depression-like behavior. However, rodents are at a large phylogenetic distance from humans. In contrast, nonhuman primates are closely similar to humans, making them an excellent candidate for SAD model. This study made the first attempt to develop SAD in rhesus macaque (Macaca mulatta) and it was found that short photoperiod conditions could lead monkeys to display depressive-like huddling behavior, less spontaneous locomotion, as well as less reactive locomotion. In addition to these depression-related behavioral changes, the physiological abnormalities that occur in patients with SAD, such as weight loss, anhedonia and hypercortisolism, were also observed in those SAD monkeys. Moreover, antidepressant treatment could reverse all of the depression-related symptoms, including depressive-like huddling behavior, less spontaneous locomotion, less reactive locomotion, weight loss, anhedonia and hypercortisolism. For the first time, this study observed the SAD symptoms in rhesus macaque, which would provide an important platform for the understanding of the etiology of SAD as well as developing novel therapeutic interventions in the future. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Jul 2015 · Behavioural brain research
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    ABSTRACT: There has been rising interest in the discovery of novel drug indications because of high costs in introducing new drugs. Many computational techniques have been proposed to detect potential drug-disease associations based on the creation of explicit profiles of drugs and diseases, while seldom research takes advantage of the immense accumulation of interaction data. In this work, we propose a matrix factorization model based on known drug-disease associations to predict novel drug indications. In addition, genomic space is also integrated into our framework. The introduction of genomic space, which includes drug-gene interactions, disease-gene interactions, and gene-gene interactions, is aimed at providing molecular biological information for prediction of drug-disease associations. The rationality lies in our belief that association between drug and disease has its evidence in the interactome network of genes. Experiments show that the integration of genomic space is indeed effective. Drugs, diseases, and genes are described with feature vectors of the same dimension, which are retrieved from the interaction data. Then a matrix factorization model is set up to quantify the association between drugs and diseases. Finally, we use the matrix factorization model to predict novel indications for drugs.
    Preview · Article · Jun 2015 · Computational and Mathematical Methods in Medicine
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    ABSTRACT: Non-human primates offer unique opportunities to study the development of depression rooted in behavioral and physiological abnormalities. This study observed adult female rhesus macaques within social hierarchies and aimed to characterize the physiological and brain abnormalities accompanying depressive-like behavior. The behaviors of 31 female rhesus macaques from 14 different breeding groups were video recorded, and the footage was analyzed using the focal animal technique. There were 13 monkeys who never displayed huddling behavior (non-huddlers). The remaining 18 monkeys were divided into two groups according the mean time spent in the huddle posture. Four monkeys were designated as high huddlers, whereas the other 14 monkeys were low huddlers. An inverse relationship was discovered between social rank and depression. High huddlers spent more time engaging in physical contact and in close proximity to other monkeys, as well as less time spontaneously and reactively locomoting, than low huddlers and/or non-huddlers. Cortisol levels measured from the hair were elevated significantly in high huddlers compared with low huddlers and non-huddlers, and the measured cortisol levels were specifically higher in high huddlers than subordinate or dominant control monkeys. Regional cerebral blood flow data revealed significant and widespread decreases in high huddlers compared with non-huddlers.
    Preview · Article · Jun 2015 · Scientific Reports
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    ABSTRACT: Sexual behavior is the dominant mode of HIV transmission in China, and young female migrants are among the populations at highest risk. This article examines how HIV-related risk behaviors among female migrants might vary according to workplace settings. Participants were young female migrants recruited from three workplace settings-factories, restaurants and entertainment venues. In a cross-sectional survey, we assessed 457 participants' sociodemographic characteristics, HIV/AIDS-related knowledge, condom use knowledge, sexual behaviors, condom use behavior and reproductive health factors. Participants working in entertainment venues were significantly more likely than those working in factories and restaurants to report sexual behavior, unprotected sex, multiple pregnancy terminations and sexually transmitted infections (STI). However, participants working in factories and restaurants reported significantly lower levels of HIV/AIDS knowledge, condom use knowledge, condom use self-efficacy and history of HIV/AIDS counseling and testing. Independent correlates of unprotected sex included employment in an entertainment venue, abortion history and sexual self-efficacy. Independent correlates of STI or genitourinary tract infection included employment in an entertainment venue, abortion history, recent migration and recent unprotected sex. These findings indicate a need for sexual and reproductive health interventions prioritizing young female migrants, and call for programs that can be incorporated into different workplace settings. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    No preview · Article · Jun 2015 · Health Promotion International
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    ABSTRACT: The aerial filamentous microalga, Trentepohlia arborum (Chlorophyta), was cultured in three habitats - an aerial, a subaerial and an aquatic one - using different types of bioreactors. The growth, carotenoid productivity, and morphologic differences of T. arborum in different habitats were investigated. The maximum specific growth rate (μ) of the alga obtained in the logarithmic phase in the subaerial habitat was 0.034 h−1. HPLC analysis also demonstrated that T. arborum accumulated a high content of carotenoids. Zeaxanthin was the primary carotenoid in subaerial culture, while β,β-carotene was dominant in aerial culture. The maximum carotenoid productivity, 67.7 mg m−2 day−1, was reached when T. arborum was cultured in the subaerial habitat under nitrogen depletion using a novel attached cultivation bioreactor. Overall, it was demonstrated that T. arborum exhibited a relatively high growth rate and carotenoid productivity under attached cultivation.
    No preview · Article · Jun 2015 · Journal of Applied Phycology
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    ABSTRACT: Biofilm cultivation of microalgae has great potential in many applications. However, the water footprint for this method has not been well assessed. This issue was explored with the microalga Haematococcus pluvialis. Only 1.25 l water is sufficient to support 1 m(2) biofilm cultivation surface. To produce 1 kg Haematococcus biomass and astaxanthin, the water footprint could be as low as 35.7 and 1440 l, respectively, by sealing the biofilm in a narrow chamber and supplying the proper amount of nutrients if the evaporation water loss was not considered. However, when loss of water by evaporation was considered, the water footprint was as low as 66.9 and 2700 l, respectively, if the chamber was aerated with CO2 at 0.014 vvm. These water footprint values are much lower than values obtained in other research work. The water footprint of biofilm microalgal cultivation can be potentially reduced by more than 90 % if the biofilm is sealed in a narrow chamber and supplied with a slow aeration of CO2 as carbon source.
    No preview · Article · May 2015 · Biotechnology Letters

  • No preview · Article · Apr 2015 · Nature Communications
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    ABSTRACT: The ability of animals to respond to life-threatening stimuli is essential for survival. Although vision provides one of the major sensory inputs for detecting threats across animal species, the circuitry underlying defensive responses to visual stimuli remains poorly defined. Here, we investigate the circuitry underlying innate defensive behaviours elicited by predator-like visual stimuli in mice. Our results demonstrate that neurons in the superior colliculus (SC) are essential for a variety of acute and persistent defensive responses to overhead looming stimuli. Optogenetic mapping revealed that SC projections to the lateral posterior nucleus (LP) of the thalamus, a non-canonical polymodal sensory relay, are sufficient to mimic visually evoked fear responses. In vivo electrophysiology experiments identified a di-synaptic circuit from SC through LP to the lateral amygdale (Amg), and lesions of the Amg blocked the full range of visually evoked defensive responses. Our results reveal a novel collicular-thalamic-Amg circuit important for innate defensive responses to visual threats.
    Full-text · Article · Apr 2015 · Nature Communications
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    ABSTRACT: In Traditional Chinese Medicine theory, syndrome is essential to diagnose diseases and treat patients, and symptom is the foundation of syndrome differentiation. Thus the combination and interaction between symptoms represent the pattern of syndrome at phenotypic level, which can be modeled and analyzed using complex network. At first, we collected inquiry information of 364 depression patients from 2007 to 2009. Next, we learned classification models for 7 syndromes in depression using naïve Bayes, Bayes network, support vector machine (SVM), and C4.5. Among them, SVM achieves the highest accuracies larger than 0.9 except for Yin deficiency. Besides, Bayes network outperforms naïve Bayes for all 7 syndromes. Then key symptoms for each syndrome were selected using Fisher's score. Based on these key symptoms, symptom networks for 7 syndromes as well as a global network for depression were constructed through weighted mutual information. Finally, we employed permutation test to discover dynamic symptom interactions, in order to investigate the difference between syndromes from the perspective of symptom network. As a result, significant dynamic interactions were quite different for 7 syndromes. Therefore, symptom networks could facilitate our understanding of the pattern of syndrome and further the improvement of syndrome differentiation in depression.
    Preview · Article · Mar 2015 · Evidence-based Complementary and Alternative Medicine
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    Yan Huang · Lin Chen · Huan Luo
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    ABSTRACT: The brain constantly creates perceptual predictions about forthcoming stimuli to guide perception efficiently. Abundant studies have demonstrated that perceptual predictions modulate sensory activities depending on whether the actual inputs are consistent with one particular prediction. In real-life contexts, however, multiple and even conflicting predictions might concurrently exist to be tested, requiring a multiprediction coordination process. It remains largely unknown how multiple hypotheses are conveyed and harmonized to guide moment-by-moment perception. Based on recent findings revealing that multiple locations are sampled alternatively in various phase of attentional rhythms, we hypothesize that this oscillation-based temporal organization mechanism may also underlie the multiprediction coordination process. To address the issue, we used well established priming paradigms in combination with a time-resolved behavioral approach to investigate the fine temporal dynamics of the multiprediction harmonization course in human subjects. We first replicate classical priming effects in slowly developing trends of priming time courses. Second, after removing the typical priming patterns, we reveal a new theta-band (∼4 Hz) oscillatory component in the priming behavioral data regardless of whether the prime was masked. Third, we show that these theta-band priming oscillations triggered by congruent and incongruent primes are in an out-of-phase relationship. These findings suggest that perceptual predictions return to low-sensory areas not continuously but recurrently in a theta-band rhythm (every 200-300 ms) and that multiple predictions are dynamically coordinated in time by being conveyed in different phases of the theta-band oscillations to achieve dissociated but temporally organized neural representations. Copyright © 2015 the authors 0270-6474/15/352830-08$15.00/0.
    Preview · Article · Feb 2015 · The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
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    ABSTRACT: c-Met has emerged as an attractive target for targeted cancer therapy due to its abnormal activation in many cancer cells. To identify high potent and selective c-Met inhibitors, we started with profiling the potency and in vitro metabolic stability of a reported hit 7. By rational design, a novel sulfonyl-pyrazolo[4,3-b]pyridine 9 with improved DMPK properties was discovered. Further elaboration of π-π stacking interactions and solvent accessible polar moieties led to a series of high potent and selective type I c-Met inhibitors. Based on in vitro and in vivo pharmacological and pharmacokinetics studies, compound 46 was selected as a preclinical candidate for further anticancer drug development.
    No preview · Article · Feb 2015 · Journal of Medicinal Chemistry
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    ABSTRACT: The signal transduction of acetylated histone can be processed through a recognition module-bromodomain. Several inhibitors targeting BRD4, one of the bromodomain members, are in clinical trials as anticancer drugs. Hereby, we report our efforts on discovery, optimization of a new series of 2-thiazolidinones as BRD4 inhibitors along our previous study. In this work, guided by crystal structure analysis, we reversed the sulfonamide group and identified a new binding mode. SAR study on this new series led to several potent BRD4 inhibitors with IC50 about 0.05-0.1 μM in FP binding assay and GI50 0.1-0.3 μM in cell based assays. To complete the lead-like assessment of this series, we further checked its effects on BRD4 downstream protein c-Myc, investigated its selectivity among five different bromodomain proteins, as well as the metabolic stability test, and reinforced the utility of 2-thiazolidinone scaffold as BET bromodomain inhibitors in novel anti-cancer drug development.
    No preview · Article · Jan 2015 · Journal of Medicinal Chemistry
  • Wei Zhang · Kou Liu · Jing Li · Lin Chen · Kuangfei Lin
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    ABSTRACT: Lead (Pb) and BDE209 (decabromodiphenyl ether) are the main contaminants at e-waste recycling sites, and their potential toxicological effects on terrestrial organisms have received extensive attention. However, the impact on earthworms of exposure to the two chemicals remains almost unknown. Therefore, indoor incubation tests were performed on control and contaminated soil samples to determine the uptake and toxicity of Pb in the presence of BDE209 to the earthworm Eisenia fetida. The results have demonstrated that the presence of BDE209 facilitated the release of Pb into soil porewater. Compared with exposure to Pb alone, simultaneous exposure to BDE209 significantly enhanced the Pb uptake rate at the level of p<0.05, while decreased the depuration rate, ultimately resulting in a larger bioaccumulation factor (BAF) value. Additionally, BDE209 addition reduced the antioxidant enzymatic activities [superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) and glutathione-s-transferase (GST)] and total antioxidant capacity (T-AOC). The decline trend in antioxidant enzymatic activities and T-AOC might explain an increase in lipid peroxidation reflected by the observed augment in malondialdehyde (MDA) level. Moreover, a biomarker of the lysosomal membrane stability, measured by neutral red retention time (NRRT), was also investigated. The NRRT obviously declined in the joint presence of BDE209, indicating a distinct time-response relationship. The results of these observations have provided a basic understanding of the potential eco-toxicological effects of joint heavy metal and BDE209 exposure on terrestrial invertebrates in a multi-contamination context of ecosystems. Copyright © 2014 Elsevier Inc. All rights reserved.
    No preview · Article · Dec 2014 · Ecotoxicology and Environmental Safety
  • Kou Liu · Lin Chen · Wei Zhang · Kuangfei Lin · Li Zhao
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    ABSTRACT: Lead (Pb) and decabromodiphenyl ether (BDE209) are the main contaminants at e-waste recycling sites, and their potential toxicological effects on terrestrial organisms have received extensive attention. However, the impacts on the oxidative perturbations and hydroxyl radical (·OH) generation in earthworms of exposure to the two chemicals remain almost unknown. Therefore, indoor incubation tests were performed on control and contaminated soil samples to determine the effects of Pb in earthworms Eisenia fetida in the presence of BDE209 through the use of several biomarkers in microcosms. The results have demonstrated that the addition of BDE209 (1 or 10 mg kg(-1)) decreased the enzymatic activities [superoxide dismutase, catalase (CAT), peroxidase] and total antioxidant capacity (T-AOC) compared with exposure to BDE209 alone (50, 250 or 500 mg kg(-1)). Electron paramagnetic resonance spectra indicated that ·OH radicals in earthworms were significantly induced by Pb in the presence of BDE209. The changing pattern of malondialdehyde (MDA) contents was accordant with that of ·OH intensity suggested that reactive oxygen species might lead to cellular lipid peroxidation. Furthermore, CAT exhibited more sensitive response to single Pb exposure than the other biomarkers, while T-AOC, ·OH and MDA might be three most sensitive biomarkers in earthworms after simultaneous exposure to Pb and BDE209. The results of these observations suggested that oxidative stress appeared in E. fetida, and it may play an important role in inducing the Pb and BDE209 toxicity to earthworms.
    No preview · Article · Nov 2014 · Ecotoxicology

Publication Stats

1k Citations
434.27 Total Impact Points

Institutions

  • 2016
    • Taiyuan University of Technology
      Yangkü, Shanxi Sheng, China
  • 2015
    • China Academy of Chinese Medical Sciences
      Peping, Beijing, China
  • 2012-2015
    • East China University of Science and Technology
      • School of Resource and Environmental Engineering
      Shanghai, Shanghai Shi, China
    • Chengdu University Of Traditional Chinese Medicine
      Hua-yang, Sichuan, China
  • 2002-2015
    • Chinese Academy of Sciences
      • • State Key Laboratory of Drug Research
      • • Institute of Biophysics
      • • Graduate School
      Peping, Beijing, China
  • 2014
    • Shanghai Veterinary Research Institute
      Shanghai, Shanghai Shi, China
  • 2013-2014
    • Wenzhou University
      Yung-chia, Zhejiang Sheng, China
  • 2008-2013
    • Tsinghua University
      • Department of Chemical Engineering
      Peping, Beijing, China
    • Beijing Tiantan Hospital
      Peping, Beijing, China
  • 2011
    • Wenzhou Medical College
      Yung-chia, Zhejiang Sheng, China
    • Peking University
      • Environmental Engineering
      Peping, Beijing, China
    • Nanjing Agricultural University
      • College of Plant Protection
      Nan-ching, Jiangsu Sheng, China
    • Capital Medical University
      • Department of Neurosurgery
      Beijing, Beijing Shi, China
  • 2009
    • Anhui Medical University
      • Department of Pharmacology
      Luchow, Anhui Sheng, China
  • 1998-2003
    • University of Science and Technology of China
      • School of Life Sciences
      Luchow, Anhui Sheng, China
  • 2001
    • University of Illinois at Chicago
      Chicago, Illinois, United States
    • Chengdu University
      Hua-yang, Sichuan, China
  • 1997
    • China University of Mining & Technology Beijing Graduate School
      Peping, Beijing, China