Bo Liu

Guangzhou University, Shengcheng, Guangdong, China

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Publications (110)388.59 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Few examples of [4+2] cycloaddition with unmasked ortho-benzoquinones (UMOBs) as carbodiene have been reported in complex molecule synthesis. Herein we report that this cycloaddition with podocarpane-type UMOB was developed and applied to construct fully functionalized bicyclo[2.2.2]octanes. Based on this methodology, divergent total syntheses of atisane-type diterpenoids, including (±)-crotobarin, crotogoudin, atisane-3β,16α-diol and 16S,17-dihydroxy-atisan-3-one, were accomplished in 14, 14, 12 and 16 steps respectively. Key elements in these total syntheses include: (1) FeCl3-catalyzed cationic cascade cyclization to construct podocarpane-type skeleton; (2) Mn(III)/Co(II)-catalyzed radical hydroxylation of alkene with high regio-, diastereo- and chemo- selectivities; (3) and a ketal-deprotection/lactone-opening/ deprotonation/lactonization cascade. Additionally, the synthetic utility of the fully functionalized bicyclo[2.2.2]octane framework was further elucidated by applying ring distortion strategy to afford different skeleton-rearranged natural product-like compounds.
    Journal of the American Chemical Society 10/2015; 137(42):151004173805000. DOI:10.1021/jacs.5b08958 · 12.11 Impact Factor
  • Jingjing Li · Sijia Li · Lan Zhang · Liang Ouyang · Bo Liu ·
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    ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the preferential death of dopaminergic neurons. In the past two decades, great progress has been made toward understanding the pathogenesis of PD; however, its precise pathogenesis still remains unclear. Recently, accumulating evidence has suggested that macroautophagy (herein referred to as autophagy) is tightly linked to PD. Dysregulation of autophagic pathways has been observed in the brains of PD patients and in animal models of PD. More importantly, a number of PD-associated proteins, such as α-synuclein, LRRK2, Parkin and PINK1 have been further revealed to be involved in autophagy. Thus, it is now acknowledged that constitutive autophagy is essential for neuronal survival and that dysregulation of autophagy leads to PD. In this review, we focus on summarizing the relationships amongst PD-associated proteins, autophagy and PD. Moreover, we also demonstrate some autophagy-modulating compounds and autophagic microRNAs in PD models, which may provide better promising strategies for potential PD therapy.
    Oncotarget 09/2015; · 6.36 Impact Factor
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    Delong Zhang · Jinhui Wang · Xian Liu · Jun Chen · Bo Liu ·
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    ABSTRACT: The coordination of spontaneous brain activity is widely enhanced relative to compensation activity in Parkinson's disease (PD) with tremor; however, the associated topological organization remains unclear. This study collected magnetic resonance imaging data from 36 participants [i.e., 16 PD patients and 20 matched normal controls (NCs)] and constructed wavelet-based functional and morphological brain networks for individual participants. Graph-based network analysis indicated that the information translation efficiency in the functional brain network was disrupted within the wavelet scale 2 (i.e., 0.063-0.125 Hz) in PD patients. Compared with the NCs, the network local efficiency was decreased and the network global efficiency was increased in PD patients. Network local efficiency could effectively discriminate PD patients from the NCs using multivariate pattern analysis, and could also describe the variability of tremor based on a multiple linear regression model (MLRM). However, these observations were not identified in the network global efficiency. Notably, the global and local efficiency were both significantly increased in the morphological brain network of PD patients. We further found that the global and local network efficiency both worked well on PD classifications (i.e., using MVPA) and clinical performance descriptions (i.e., using MLRM). More importantly, functional and morphological brain networks were highly associated in terms of network local efficiency in PD patients. This study sheds lights on network disorganization in PD with tremor and helps for understanding the neural basis underlying this type of PD.
    Frontiers in Aging Neuroscience 09/2015; 7:169. DOI:10.3389/fnagi.2015.00169 · 4.00 Impact Factor
  • Guili Zhu · Rong Liu · Bo Liu ·
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    ABSTRACT: Atisane-type compounds and related natural products are attractive for their molecular skeletons and pharmaceutical bioactivities. This review summarizes total syntheses of atisane-type diterpenoids and related diterpenoid alkaloids. 1 Introduction 2 Total Synthesis and Synthetic Studies of Atisane-Type Diterpenoids and Related Diterpenoid Alkaloids 2.1 Ionic Methods 2.1.1 SN2 Substitution Reaction 2.1.2 Aldol Reaction 2.1.3 Intramolecular Double Michael Addition 2.2 Free-Radical Methods 2.2.1 Free-Radical Rearrangement 2.2.2 Free-Radical Addition 2.3 Diels-Alder Cycloaddition 3 Conclusion.
    Synthesis 09/2015; 47(18):2691-2708. DOI:10.1055/s-0034-1378743 · 2.69 Impact Factor
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    ABSTRACT: The aim of this study was to explore the autophagy-related protein 4B(ATG4B) and its targeted candidate agonist in triple-negative breast cancer (TNBC) therapy. In this study, the identification of Atg4B as a novel breast cancer target for screening candidate small molecular agonists was performed by phylogenetic analysis, network construction, molecular modelling, molecular docking and molecular dynamics (MD) simulation. In vitro, MTT assay, electron microscopy, western blot and ROS measurement were used for validating the efficacy of the candidate compounds. We used the phylogenetic analysis of Atg4B and constructed their protein-protein interaction (PPI) network. Also, we screened target compounds of Atg4 proteins from Drugbank and ZINC. Flubendazole was validated for its anti-proliferative efficacy in MDA-MB-231 cells. Further MD simulation results supported the stable interaction between Flubendazole and Atg4B. Moreover, Flubendazole induced autophagy and increased ROS production. In conclusion, in silico analysis and experimental validation together demonstrate that Flubendazole can target Atg4B in MDA-MB-231 cells and induce autophagy, which may shed light on the exploration of this compound as a potential new Atg4B targeted drug for future TNBC therapy.
    Molecular BioSystems 08/2015; 11(11). DOI:10.1039/c5mb00466g · 3.21 Impact Factor
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    Shu-ya Wang · Qi-jia Yu · Ru-dian Zhang · Bo Liu ·

  • Li Yang · Jing Feng · Jinpeng Li · Bo Liu ·
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    ABSTRACT: Abstract The highly diastereoselective total synthesis of heliespirone B, an oxaspirocyclic compound isolated from the leaves of Helianthus annuus, has been accomplished from (R)-curcuphenol. Key transformations include the formation of an oxaspirocyclic structure via a highly diastereoselective oxa-Michael reaction.
    Tetrahedron Letters 07/2015; 56(34):4931-4933. DOI:10.1016/j.tetlet.2015.06.093 · 2.38 Impact Factor
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    ABSTRACT: Autophagy, referring to an evolutionarily conserved, multi-step lysosomal degradation process, has been well-known to be initiated by Unc-51 like kinase 1 (ULK1) with some links to Parkinson's disease (PD). MicroRNAs (miRNAs), small and non-coding endogenous RNAs 22 ~ 24 nucleotides (nt) in length, have been demonstrated to play an essential role for modulating autophagy. Recently, the relationships between miRNAs and autophagy have been widely reported in PD; however, how microRNAs regulate autophagy still remains in its infancy. Thus, in this study, we computationally constructed the ULK1-regulated autophagic kinase subnetwork in PD and further identified ULK1 able to negatively regulate p70(S6K) in starvation-induced autophagy of neuroblastoma SH-SY5Y cells. Combination of in silico prediction and microarray analyses, we identified that miR-4487 and miR-595 could target ULK1 and experimentally verified they could negatively or positively regulate ULK1-mediated autophagy. In conclusion, these results may uncover the novel ULK1-p70(S6K) autophagic pathway, as well as miR-4487 and miR-595 as new ULK1 target miRNAs. Thus, these findings would provide a clue to explore ULK1 and its target miRNAs as potential biomarkers in the future PD therapy.
    Scientific Reports 07/2015; 5:11035. DOI:10.1038/srep11035 · 5.58 Impact Factor
  • Jingjing Li · Sijia Li · Lan Zhang · Liang Ouyang · Bo Liu ·

    Oncotarget 07/2015; DOI:10.18632/oncotarget.5803 · 6.36 Impact Factor
  • Jiao Xu · Bo Liu ·
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    ABSTRACT: First total synthesis of norleucosceptroids F and G has been achieved through key steps of Michael–Aldol cascade, oxa-Michael cyclization–dehydration–deprotection cascade and cross metathesis (CM), this work developed a general and concise method to the synthesis of leucosceptroid and norleucosceptroid.
    Chinese Chemical Letters 07/2015; 26(11). DOI:10.1016/j.cclet.2015.07.004 · 1.59 Impact Factor
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    ABSTRACT: In this paper, the pentacyclic skeleton of hirsutellone B including the paracyclophane was constructed via a tandem IMDA/ketene-trapping scenario with the proper stereochemistry. Alternatively, from the common intermediate 4, we completed a formal synthesis of hirsutellone B.
    Tetrahedron 06/2015; 71(22). DOI:10.1016/j.tet.2015.01.002 · 2.64 Impact Factor
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    ABSTRACT: Accumulating evidence demonstrates existence of cancer stem cells (CSCs), which are suspected of contributing to cancer cell self-renewal capacity and resistance to radiation and/or chemotherapy. Including evasion of apoptosis and autophagic cell death, CSCs have revealed abilities to resist cell death, making them appealing targets for cancer therapy. Recently, molecular mechanisms of apoptosis and of autophagy in CSCs have been gradually explored, comparing them in stem cells and in cancer cells; distinct expression of these systems in CSCs may elucidate how these cells exert their capacity of unlimited self-renewal and hierarchical differentiation. Due to their proposed ability to drive tumour initiation and progression, CSCs may be considered to be potentially useful pharmacological targets. Further, multiple compounds have been verified as triggering apoptosis and/or autophagy, suppressing tumour growth, thus providing new strategies for cancer therapy. In this review, we summarized regulation of apoptosis and autophagy in CSCs to elucidate how key proteins participate in control of survival and death; in addition, currently well-studied compounds that target CSC apoptosis and autophagy are selectively presented. With increasing attention to CSCs in cancer therapy, researchers are now trying to find responses to unsolved questions as unambiguous as possible, which may provide novel insight into future anti-cancer regimes. © 2015 John Wiley & Sons Ltd.
    Cell Proliferation 05/2015; 48(4). DOI:10.1111/cpr.12191 · 3.12 Impact Factor
  • Yi Chen · Jian Huang · Bo Liu ·

    Apoptosis 05/2015; 20(7). DOI:10.1007/s10495-015-1133-1 · 3.69 Impact Factor
  • Jing Feng · Bo Liu ·

    ChemInform 05/2015; 46(19). DOI:10.1002/chin.201519295
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    ABSTRACT: As a conserved protein interaction module that recognizes and binds to acetylated lysine, bromodomain (BRD) contains a deep, largely hydrophobic acetyl lysine binding site. Proteins that share the feature of containing two BRDs and an extra-terminal domain belong to BET family, including BRD2, BRD3, BRD4 and BRDT. BET family proteins perform transcription regulatory function under normal conditions, while in cancer, they regulate transcription of several oncogenes, such as c-Myc and Bcl-2. Thus, targeting BET proteins may be a promising strategy, and intense interest of BET proteins has fueled the development of structure-based bromodomain inhibitors in cancer. In this review, we focus on summarizing several small-molecule BET inhibitors and their relevant anti-tumor mechanisms, which would provide a clue for exploiting new targeted BET inhibitors in the future cancer therapy.
    Oncotarget 03/2015; 6(8):5501-5516. DOI:10.18632/oncotarget.3551 · 6.36 Impact Factor
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    ABSTRACT: A diastereoselective Pd-catalyzed intramolecular cyclopropanation of alkenes with unstabilized allylic tosylhydrazones was developed. This methodology provides an efficient entry toward synthesis of the bicyclo[3.1.0] hexane system with an exo-double bond, and sets the basis for future elaboration of more complex polycyclic motifs.
    Chemical Communications 03/2015; 51(28). DOI:10.1039/c5cc00235d · 6.83 Impact Factor
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    ABSTRACT: The aim of this study was to discover a small molecule activator BL-AD008 targeting AMPK/ZIPK and inducing apoptosis in cervical cancer. In this study, we systematically constructed the global protein-protein interaction (PPI) network and predicted apoptosis-related protein connections by the Naïve Bayesian model. Then, we identified some classical apoptotic PPIs and other previously unrecognized PPIs between apoptotic kinases, such as AMPK and ZIPK. Subsequently, we screened a series of candidate compounds targeting AMPK/ZIPK, synthesized some compounds and eventually discovered a novel dual-target activator (BL-AD008). Moreover, we found BL-AD008 bear remarkable anti-proliferative activities toward cervical cancer cells and could induce apoptosis by death-receptor and mitochondrial pathways. Additionally, we found that BL-AD008-induced apoptosis was affected by the combination of AMPK and ZIPK. Then, we found that BL-AD008 bear its anti-tumor activities and induced apoptosis by targeting AMPK/ZIPK in vivo. In conclusion, these results demonstrate the ability of systems biology network to identify some key apoptotic kinase targets AMPK and ZIPK; thus providing a dual-target small molecule activator (BL-AD008) as a potential new apoptosis-modulating drug in future cervical cancer therapy.
    Oncotarget 03/2015; 6(10). DOI:10.18632/oncotarget.3513 · 6.36 Impact Factor
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    ABSTRACT: The present study examined directional connections in the brain among resting-state networks (RSNs) when the participant had their eyes open (EO) or had their eyes closed (EC). The resting-state fMRI data were collected from 20 healthy participants (9 males, 20.17 ± 2.74 years) under the EO and EC states. Independent component analysis (ICA) was applied to identify the separated RSNs (i.e., the primary/high-level visual, primary sensory-motor, ventral motor, salience/dorsal attention, and anterior/posterior default-mode networks), and the Gaussian Bayesian network (BN) learning approach was then used to explore the conditional dependencies among these RSNs. The network-to-network directional connections related to EO and EC were depicted, and a support vector machine (SVM) was further employed to identify the directional connection patterns that could effectively discriminate between the two states. The results indicated that the connections among RSNs are directionally connected within a BN during the EO and EC states. The directional connections from the salience network (SN) to the anterior/posterior default-mode networks and the high-level to primary-level visual network were the obvious characteristics of both the EO and EC resting-state BNs. Of the directional connections in BN, the directional connections of the salience and dorsal attention network (DAN) were observed to be discriminative between the EO and EC states. In particular, we noted that the properties of the salience and DANs were in opposite directions. Overall, the present study described the directional connections of RSNs using a BN learning approach during the EO and EC states, and the results suggested that the directionality of the attention systems (i.e., mainly for the salience and the DAN) in resting state might have important roles in switching between the EO and EC conditions.
    Frontiers in Human Neuroscience 02/2015; 9:81. DOI:10.3389/fnhum.2015.00081 · 3.63 Impact Factor
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    Delong Zhang · Xian Liu · Jun Chen · Bo Liu · Jinhui Wang ·
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    ABSTRACT: Parkinson's disease (PD) is a clinically heterogeneous disease in the symptomatology dominated by tremor, akinesia, or rigidity. Focusing on PD patients with tremor, this study investigated their discoordination patterns of spontaneous brain activity by combining voxel-wise centrality, seed-based functional connectivity, and network efficiency methods. Sixteen patients and 20 matched healthy controls (HCs) were recruited and underwent structural and resting-state functional MRI scan. Compared with the HCs, the patients exhibited increased centrality in the frontal, parietal, and occipital regions while decreased centrality in the cerebellum anterior lobe and thalamus. Seeded at these regions, a distributed network was further identified that encompassed cortical (default mode network, sensorimotor cortex, prefrontal and occipital areas) and subcortical (thalamus and basal ganglia) regions and the cerebellum and brainstem. Graph-based analyses of this network revealed increased information transformation efficiency in the patients. Moreover, the identified network correlated with clinical manifestations in the patients and could distinguish the patients from HCs. Morphometric analyses revealed decreased gray matter volume in multiple regions that largely accounted for the observed functional abnormalities. Together, these findings provide a comprehensive view of network disorganization in PD with tremor and have important implications for understanding neural substrates underlying this specific type of PD.
    Frontiers in Aging Neuroscience 02/2015; 7. DOI:10.3389/fnagi.2015.00006 · 4.00 Impact Factor
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    ABSTRACT: Wound dressing is critical important for cutaneous wound healing. However, the application of current products is limited due to poor mechanical property, unsuitable water vapor transmission rate (WVTR), poor anti-infective property or poor biocompatibility, etc. In the present study, a microporous silicone rubber membrane bilayer (SRM-B) composed of two layers with different pore sizes was prepared. The physical properties, the influences of pore structure on the bacterial penetration, the cell adhesion and proliferation were studied. Lastly, the effects of the SRM-B on the healing of a mouse full-thickness wound were examined. The data showed that the small pore upper layer of SRM-B could effectively prevent the bacterial invasion, as well as properly keep the water vapor transmission rate; the large pore lower layer of SRM-B could promote the cell adhesion and proliferation. The in vivo results showed that SRM-B could significantly enhance wound re-epithelialization and contraction, which accelerated the wound healing. Our data suggested that the SRM-B, with different particular pore sizes, could serve as a kind of promising wound dressing.
    Biomaterials 02/2015; 40. DOI:10.1016/j.biomaterials.2014.10.077 · 8.56 Impact Factor

Publication Stats

2k Citations
388.59 Total Impact Points


  • 2015
    • Guangzhou University
      Shengcheng, Guangdong, China
  • 2014-2015
    • China Pharmaceutical University
      • Division of Medicinal Chemistry
      Nan-ching-hsü, Jiangxi Sheng, China
  • 2008-2015
    • Sichuan University
      • • State Key Laboratory of Polymer Material Engineering
      • • College of Chemistry
      • • College of Life Sciences
      Hua-yang, Sichuan, China
  • 2013
    • Sun Yat-Sen University of Medical Sciences
      Shengcheng, Guangdong, China
    • State Key Laboratory of Medical Genetics of China
      Ch’ang-sha-shih, Hunan, China
  • 2012-2013
    • Guangzhou University of Traditional Chinese Medicine
      Shengcheng, Guangdong, China