Jun Zhu

National Pharmaceutical Engineering Research Center, Shanghai, Shanghai Shi, China

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Publications (51)419.32 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A facile approach was proposed to prepare Silk Fibroin (SF) and Hyaluronic Acid (HA) composite films from aqueous solution without crosslinking or any post treatment. Only by controlling the HA content and film formation temperature during the film casting, the HA/SF films with different composition were prepared. The films were then characterized by structural characteristics, thermal stability, morphology, water stability, water absorption, mechanical properties. After immersing in water for 24 hours, all of the films showed good structural integrity. The degradation rate of the HA/SF films in protease XIV can be controlled by changing the film formation temperature and HA content. Decreasing the temperature and adding HA resulted in the rapid release of VEGF (vascular endothelial growth factor) from the HA/SF films. Overall, the 5% HA/SF films formed at 37 °C with more rapid VEGF release exhibited great potential in drug delivery, especially when the rapid vascularization was needed.
    No preview · Article · Jan 2016 · Carbohydrate Polymers
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    ABSTRACT: A universal platform with Mn doping and hyaluronic acid (HA) modification, based on mesoporous silica (mSiO2), was designed and used as a basic multifunctional material with magnetic resonance (MR) imaging. Furthermore, we added flexible functions through the addition of functional molecules. Specially, two typical compounds, hydrophobic perfluorooctyl bromide (PFOB) and hydrophilic doxorubicin (DOX), were loaded into the channels to obtain PFOB@Mn@mSiO2@HA (PMMH) or DOX@Mn@mSiO2@HA (DMMH) nanoparticles for dual-mode imaging or imaging and therapy, respectively. The PMMH and DMMH nanoparticles were highly targeted to the lymph system in vitro and in vivo. MR and ultrasound imaging of PMMH nanoparticles were performed in the lymph system, while MR imaging and chemotherapy of DMMH nanoparticles was used to detect cancer. These results showed that both PMMH and DMMH nanoparticles can be designed with high lymph targeting efficiency. PMMH nanoparticles are a dual-mode contrast agent for both ultrasound and MR imaging for the lymph system and DMMH nanoparticles are powerful agents for the combined diagnosis and therapy of cancer in vivo.[Figure not available: see fulltext.] © 2015 Tsinghua University Press and Springer-Verlag Berlin Heidelberg
    No preview · Article · Nov 2015 · Nano Research
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    ABSTRACT: CCAAT/enhancer-binding protein α (C/ebpα) is a transcription factor that plays important roles in the regulation of hepatogenesis, adipogenesis and hematopoiesis. Disruption of the C/EBPα gene in mice leads to disturbed liver architecture and neonatal death due to hypoglycemia. However, the precise stages of liver development affected by C/ebpα loss are poorly studied. Using the zebrafish embryo as a model organism, we show that inactivation of the cebpa gene by TALENs results in a small liver phenotype. Further studies reveal that C/ebpα is distinctively required for hepatic outgrowth but not for hepatoblast specification. Lack of C/ebpα leads to enhanced hepatic cell proliferation and subsequent increased cell apoptosis. Additional loss of p53 can largely rescue the hepatic defect in cebpa mutants, suggesting that C/ebpα plays a role in liver growth regulation via the p53 pathway. Thus, our findings for the first time demonstrate a stage-specific role for C/ebpα during liver organogenesis.
    Preview · Article · Oct 2015 · Scientific Reports
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    ABSTRACT: Perfluorocarbon (PFC), a kind of oxygen carriers, is encapsulated in PLGA-PEG to prepare PLGA-PEG/PFC emulsion for highly efficient reoxygenation to cell and organism. HCT 116 cells are used as a model cell, whose viability has a significant enhancement after reoxygenation with PLGA-PEG/PFC emulsion because of the sufficient and timely oxygen supply. Meanwhile, hypoxia-reoxygenation injury will happen along with cell hypoxia-reoxygenation treatment, which is reflected by increasing ROS in cells. However, the integration of intracellular ROS and cell viability implies that the degree of hypoxia-reoxygenation injury is sublethal to HCT116 cells when the concentration of PLGA-PEG/PFC emulsion is lower than 0.2 mg/mL. Furthermore, the change of the expression level of HIF-1α is similar to that of cell viability during reoxygenation, which suggests that HIF-1α or its downstream proteins may make a significant contribution to cell viability. In vivo oxygen supply is assessed in rats through pulmonary delivery, which shows that PLGA-PEG/PFC emulsion can supply oxygen to rats and improve rats' lungs ventilation.
    No preview · Article · Jul 2015 · ACS Applied Materials & Interfaces
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    ABSTRACT: A novel MRI contrast agent, hyaluronic acid gadolinium complex (HA-Gd-DTPA) nanospheres, is prepared by the synthesis of hyaluronic acid gadolinium complexes and their assembly. The physicochemical properties are characterized, and the lymphatic targeting in vitro and in vivo are also evaluated. The results show that the HA-Gd-DTPA nanospheres with suitable and stable physicochemical properties could be used for in vivo lymphatic targeting studies. Furthermore, the HA-Gd-DTPA nanospheres have obviously higher relaxation efficiency and MRI contrast between blood vessel and lymph vessel in rabbit than that of Magnevist. Thus, the novel MRI contrast agent can be taken up selectively by lymphatic system and used as a potential MRI contrast agents in lymphatic system.
    No preview · Article · Jul 2015 · Chinese Journal of Chemistry
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    ABSTRACT: Dysregulation of ribosome biogenesis causes human diseases, such as Diamond-Blackfan anemia, del (5q-) syndrome and bone marrow failure. However, the mechanisms of blood disorders in these diseases remain elusive. Through genetic mapping, molecular cloning and mechanism characterization of the zebrafish mutant cas002, we reveal a novel connection between ribosomal dysfunction and excessive autophagy in the regulation of hematopoietic stem/progenitor cells (HSPCs). cas002 carries a recessive lethal mutation in kri1l gene that encodes an essential component of rRNA small subunit processome. We show that Kri1l is required for normal ribosome biogenesis, expansion of definitive HSPCs and subsequent lineage differentiation. Through live imaging and biochemical studies, we find that loss of Kri1l causes the accumulation of misfolded proteins and excessive PERK activation-dependent autophagy in HSPCs. Blocking autophagy but not inhibiting apoptosis by Bcl2 overexpression can fully rescue hematopoietic defects, but not the lethality of kri1l(cas002) embryos. Treatment with autophagy inhibitors (3-MA and Baf A1) or PERK inhibitor (GSK2656157), or knockdown of beclin1 or perk can markedly restore HSPC proliferation and definitive hematopoietic cell differentiation. These results may provide leads for effective therapeutics that benefit patients with anemia or bone marrow failure caused by ribosome disorders.Cell Research advance online publication 3 July 2015; doi:10.1038/cr.2015.81.
    Preview · Article · Jul 2015 · Cell Research
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    ABSTRACT: Imbalance between T-helper 17 (Th17) cells and regulatory T (Treg) cells is causally linked to the development of rheumatoid arthritis (RA). In this study, we tested the hypothesis that electroacupuncture (EA) confers therapeutic benefits in RA through activation of vasoactive intestinal peptide (VIP)-dependent signalling and restoration of the Th17/Treg cell balance. A collagen-induced arthritis (CIA) model was induced in Sprague-Dawley rats by injection of bovine type II collagen in incomplete Freund's adjuvant on day 0 and day 7. Three days after the second injection, EA was given at acupuncture points GB39 and ST36 three times per week for 4 weeks. To block VIP signalling, [D-P-Cl-Phe(6)-Leu(17)]-VIP, a VIP receptor antagonist, was administered intraperitoneally 30 min before EA. Inflammatory and pathological responses in the joint were assessed. Synovial VIP receptor mRNA levels and Treg and Th17 cell frequencies in the spleen were determined. EA significantly reduced the severity of CIA, as evidenced by reduced paw volumes, arthritis scores and inflammation scores. EA significantly increased mRNA expression of the VIP receptor VPAC1 and led to an elevation in CD4(+)FOXP3(+) Treg cell frequency and a reduction in CD4(+)IL17(+) Th17 cell frequency. Pre-injection of a VIP receptor antagonist significantly reversed EA-induced expansion of Treg cells, but did not alter the frequencies of Th17 cells. EA exerts anti-inflammatory effects in a collagen-induced rat model of arthritis. These effects appear to be mediated through activation of VIP signalling and re-establishment of the Th17/Treg cell balance. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    No preview · Article · May 2015 · Acupuncture in Medicine
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    ABSTRACT: The small ubiquitin-related modifier (SUMO) participates in various cellular processes, including maintenance of genome integrity, nuclear transport, transcription and signal transduction. However, the biological function of sumoylation in hematopoiesis has not been fully explored. We show here that definitive hematopoietic stem/progenitor cells (HSPCs) are depleted in SUMO-deficient zebrafish embryos. Impairment of sumoylation attenuates HSPC generation and proliferation. The hyposumoylation triggered HSPC defects are CCAAT/enhancer-binding protein α (C/ebpα) dependent. Critically, a SUMO-C/ebpα fusion rescues the defective hematopoiesis in SUMO-deficient embryos, at least in part through restored runx1 expression. While C/ebpα-dependent transcription is involved in myeloid differentiation, our studies here reveal that C/ebpα sumoylation is essential for HSPC development during definitive hematopoiesis.
    Full-text · Article · Mar 2015 · Scientific Reports
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    ABSTRACT: Multimodality molecular imaging has recently attracted much attention, because it can take advantage of individual imaging modalities by fusing together information from several molecular imaging techniques. Herein, we report a bifunctional contrast agent connecting MR and luminescent imaging. The bifunctional contrast agent, carbon@Gd-DTPA microspheres, arises from carbon microspheres, which is synthesized on a large scale through a Na3cit-assisted solution route. The T1-agent, Gd-DTPA, is then conjugated to the carbon microspheres through N-ethyl-N9-[3-(dimethylamino)propyl]carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) coupling chemistry using surface absorbed Na3cit molecules as an intermedium. Meanwhile, a formation mechanism of the carbon microspheres has been suggested. Furthermore, we also prove that the application of the carbon@Gd-DTPA bifunctional contrast agents for MR imaging and luminescent imaging can be established successfully. These results show that the primary Na3cit molecules have been confirmed to serve triplicate roles as an oriented agent to produce carbon microsphere, an intermedium to conjugate Gd-DTPA and surface passivation agents to improve photoluminescence.
    No preview · Article · Mar 2015 · RSC Advances
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    ABSTRACT: DNA methyltransferase 1 (Dnmt1) regulates expression of many critical genes through maintaining parental DNA methylation patterns on daughter DNA strands during mitosis. It is essential for embryonic development and diverse biological processes, including maintenance of hematopoietic stem and progenitor cells (HSPCs). However, the precise molecular mechanism of how Dnmt1 is involved in HSPC maintenance remains unexplored. An N-ethyl-N-nitrosourea (ENU)-based genetic screening was performed to identify putative mutants with defects in definitive HSPCs during hematopoiesis in zebrafish. The expression of hematopoietic markers was analyzed via whole mount in situ hybridization assay (WISH). Positional cloning approach was carried out to identify the gene responsible for the defective definitive hematopoiesis in the mutants. Analyses of the mechanism were conducted by morpholino-mediated gene knockdown, mRNA injection rescue assays, anti-phosphorylated histone H3 (pH3) immunostaining and TUNEL assay, quantitative real-time PCR, and bisulfite sequencing analysis. A heritable mutant line with impaired HSPCs of definitive hematopoiesis was identified. Positional cloning demonstrated that a stop codon mutation was introduced in dnmt1 which resulted in a predicted truncated Dnmt1 lacking the DNA methylation catalytic domain. Molecular analysis revealed that expression of CCAAT/enhancer-binding protein alpha (C/ebpa) was upregulated, which correlated with hypomethylation of CpG islands in the regulation regions of cebpa gene in Dnmt1 deficient HSPCs. Overexpression of a transcriptional repressive SUMO-C/ebpa fusion protein could rescue hematological defects in the dnmt1 mutants. Finally, dnmt1 and cebpa double null embryos exhibited no obvious abnormal hematopoiesis indicated that the HSPC defects triggered by dnmt1 mutation were C/ebpa dependent. Dnmt1 is required for HSPC maintenance via cebpa regulation during definitive hematopoiesis in zebrafish.
    Preview · Article · Feb 2015 · Journal of Hematology & Oncology
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    ABSTRACT: Acute promyelocytic leukemia (APL) is a model disease for targeted therapy. APL is caused by a variety of fusion proteins, all implicating the retinoic acid receptor alpha (RARA). The promyelocytic gene (PML)/RARA fusion is by far the most frequent, present in 99 % of patients. Two unconventional drugs, retinoic acid (RA) and arsenic trioxide were first shown to exhibit extraordinary clinical activity and later found to directly target PML/RARA. RA binds PML/RARA via its RARA moiety, activates transcription and degrades PML/RARA. Arsenic only degrades the fusion protein by targeting its PML part. Mouse modeling in APL has allowed an unprecedented level of understanding of the disease pathogenesis and basis for therapy response, highlighting the key role of PML/RARA degradation in the latter. The combination of RA and arsenic definitively eradicate the disease in mice and in most patients. APL thus represents a paradigm for oncoprotein-targeted cures.
    No preview · Article · Jan 2015
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    ABSTRACT: The ability of drug release from SF materials was governed largely by their secondary structure. It is known that the breakage degree of the peptide chain during the silk fibroin (SF) dissolution can affect the structure, property, and applications of SF materials. To deeply understand this effect, we designed a reaction system based on CaCl2/H2O/C2H5OH ternary solvent with different ethanol content to obtain the regenerated SF films with different morphologies and secondary structures. The results showed that the globule-like nanostructure was observed in all regenerated SF films, and their size decreased significantly with reducing the ethanol content in the solvent. Correspondingly, the β-sheet structure content of the SF films increased. In addition, the contact angle and the elongation ratio increased, and water absorption decreased significantly with decreasing the ethanol content in the solvent. The accumulated release percents of doxorubicin from these SF films were significantly different with increasing the time. With smaller nanostructure size and more β-sheet content, the SF films had a slower drug release at the beginning. This study indicated the importance of the ethanol content in the solvent in controlling the structure and properties of the regenerated SF films, which would improve the application of SF in drug delivery.
    Full-text · Article · Dec 2014 · ACS Applied Materials & Interfaces
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    ABSTRACT: FC-77, a kind of perfluorocarbon compound, was inclusion-complexed with β-cyclodextrin (β-CD) in an attempt to improve their stability and bioavailability. Analyses by powder X-ray diffraction (XRD), thermogravimetric analyses (TGA), differential scanning calorimeter (DSC), Fourier transform infrared spectrum (FT-IR), transmission electron microscopy (TEM) and dynamic light scattering (DLS) proved the formation of the inclusion complex between FC-77 and β-CD, and high performance ion chromatography revealed that FC-77 content in the inclusion complex is 9.77% at 5:1 molar ratio of β-CD and FC-77. Furthermore, the inclusion constant and capacity were evaluated by UV-vis absorption spectroscopy and double reciprocal method. The results show that the nanoparticle of 1:1 FC-77/β-CD inclusion complex with an inclusion constant of 242.7 M−1 was formed. Furthermore, ultrasound imaging experiments were performed to demonstrate biomedical application of FC-77/β-CD inclusion complex, which indicated that FC-77/β-CD inclusion complex could be employed as an ultrasound contrast agent for increasing ultrasound contrast.
    No preview · Article · Dec 2014 · RSC Advances
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    ABSTRACT: PML/RARA is the oncoprotein driving acute promyelocytic leukemia (APL). It suppresses genes expression by recruitment of a number of transcriptional repressors, resulting in differentiation block and malignant transformation of hematopoietic cells. Here, we found that mice primary hematopoietic progenitor cells (HPCs), transduced by DNA-binding-defective PML/RARA mutants, were deficient in colony formation. Further experiments showed that DNA-binding-defective PML/RARA mutants could not repress the transcription of retinoic acid regulated genes. Intriguingly, there were no significant differences of the micro-speckled intracellular distribution between the mutants and wild-type PML/RARA. Some retinoic acid target genes regulated by PML/RARA are involved in not only differentiation block but also hematopoietic cell self-renewal. Altogether, our data demonstrate that direct DNA-binding is essential for PML/RARA to immortalize hematopoietic cells, while disruption of PML-nuclear body does not seem to be a prerequisite for hematopoietic cell transformation.
    Full-text · Article · Aug 2014 · PLoS ONE
  • Jun Zhu · Juan Zhou · Daixu Wei · Shiyuan Liu
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    ABSTRACT: Nearly monodisperse CdS hierarchical hollow nanospheres have been synthesized on a large scale through a Na3cit-assisted solution route, in which hollow structure and CdS building blocks is applied as drug carrier and fluorescent capability, respectively. T1-agents, Gd-DTPA is then conjugated to CdS hierarchical hollow nanospheres through EDC/NHS coupling chemistry used as surface absorbed Na3cit molecule as an intermedium. Thus, the multifunctional magnetic-fluorescent CdS/Gd-DTPA hierarchical hollow nanospheres (CdS@Gd-DTPA) are formed, which combines magnetic resonance imaging (MRI), fluorescent imaging and drug delivery into one system. The as-prepared products are characterized in detail by Powder X-ray diffraction, transmission electron microscope, scanning electron microscope, and Fourier transform infrared spectrometry. The room-temperature photoluminescent spectra and T1-weighted maps of the obtained CdS@Gd-DTPA are carried out by fluorescence spectrophotometer and a 3T MRI scanner, respectively. The results indicate that the as-prepared product is potential candidates for simultaneous disease diagnosis and therapy by combining the multiplexing imaging capability.
    No preview · Article · May 2013 · CrystEngComm
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    ABSTRACT: A self-inflating hydrogel based on silk fibroin (SF) and poly(sodium acrylate) (PAAS) was synthesized by the free radical copolymerization. Furthermore, its potential as a tissue implant with minimally invasive treatment was investigated. The effects of the weight ratio of SF to AA (acrylic acid) on the structure, swelling properties and mechanical properties of the PAAS-SF semi-IPN hydrogels were investigated. In addition, the loading and release of amoxicillin of the PAAS-SF semi-IPN hydrogels were studied. With increasing SF content in the hydrogels, the swelling ratio and the rate of drug release increased, while the compressive strength decreased. It was observed that (83.4±0.9)% of the loaded drug was released within 120 h for the PAAS-SF20 semi-IPN hydrogels. The results revealed that the self-inflating PAAS-SF semi-IPN hydrogels with high swelling ratio and good drug releasing capabilities may have potential in the drug delivery or other implantable materials.
    Full-text · Article · May 2013 · Chinese Journal of Organic Chemistry
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    ABSTRACT: Superparamagnetic iron oxide nanoparticles with narrow size distributions were successfully prepared in large scale by a facile one-pot synthetic method in the presence of hydrophilic polymers, such as polyethylene glycol diacid (HOOC-PEG-COOH) and poly(acrylic acid) (PAA). The as-prepared products were investigated in detail by powder X-ray diffraction (XRD), thermogravimetric analyses (TGA), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), dynamic light scattering (DLS), and vibrating sample magnetometer (VSM). The interaction between polymers and iron oxide nanoparticles was investigated using Fourier transform infrared spectrometry (FT-IR). The results show that polymers can be attached onto the surface of iron oxide nanoparticle by bridging coordination and monodentate fashion, respectively. The interaction affects iron oxide nanoparticle properties significantly, such as XRD diffraction intensity, hydrodynamic diameter, isoelectric point, and saturation magnetization. Furthermore, the results of in vitro experiments indicated that iron oxide-PEG-COOH nanoparticle is more cytotoxic than iron oxide-PAA nanoparticle due to different coordinating modes.
    No preview · Article · Mar 2013 · Chinese Journal of Chemistry
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    ABSTRACT: The relative genetic simplicity of leukaemias, the development of which likely relies on a limited number of initiating events has made them ideal for disease modelling, particularly in the mouse. Animal models provide incomparable insights into the mechanisms of leukaemia development and allow exploration of the molecular pillars of disease maintenance, an aspect often biased in cell lines or ex vivo systems. Several of these models, which faithfully recapitulate the characteristics of the human disease, have been used for pre-clinical purposes and have been instrumental in predicting therapy response in patients. We plea for a wider use of genetically defined animal models in the design of clinical trials, with a particular focus on reassessment of existing cancer or non-cancer drugs, alone or in combination.
    Preview · Article · Feb 2013 · Molecular oncology
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    ABSTRACT: In(OH)3 nanomaterials with different morphologies or hierarchical structures, such as nanoparticles, monodispersed hierarchical nanocubes and nanospheres, have been successfully synthesized via a ligand-assisted aqueous process. The shape and size of these as-prepared architectures can be tuned effectively by controlling the reaction conditions, such as the molar ratio of ligand/In3+ and different ligands. Further studies reveal that both Na3cit and urea are necessary for the formation of monodispersed hierarchical nanospheres and nanocubes. Furthermore, In2O3 nanoparticles and monodispersed hierarchical nanocubes and nanospheres with well-defined morphologies of the precursors can be also obtained by annealing the corresponding In(OH)3 samples. The gas sensing properties of the as-prepared In2O3 samples demonstrate that hierarchical In2O3 architectures exhibit a superior response to ethanol gas, and the hierarchical In2O3 nanocubes have excellent selectivity and sensitivity. Further more, XPS spectra and N2 adsorption-desorption isotherms achieve a deeper understanding of the effects of the final product morphologies on their gas sensing properties.
    Preview · Article · Jan 2013 · Journal of Materials Chemistry
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    ABSTRACT: The regulation of hematopoiesis is generally evolutionarily conserved from zebrafish to mammals, including hematopoietic stem cell formation and blood cell lineage differentiation. In zebrafish, primitive granulocytes originate at two distinct regions, the anterior lateral plate mesoderm (A-LPM) and the intermediate cell mass (ICM). Few studies in the zebrafish have examined genes specifically required for the granulocytic lineage. In this study, we identified the responsible gene for a zebrafish mutant that has relatively normal hematopoiesis, except decreased expression of the granulocyte-specific gene mpx. Positional cloning revealed that phospholipase C gamma-1 (plcg1) was mutated. Deficiency of plcg1 function specifically affected development of granulocytes, especially the maturation process. These results suggested that plcg1 functioned specifically in zebrafish ICM granulopoiesis for the first time. Our studies suggest that specific pathways regulate the differentiation of the hematopoietic lineages.
    Preview · Article · Dec 2012 · Developmental Biology

Publication Stats

2k Citations
419.32 Total Impact Points

Institutions

  • 2013-2016
    • National Pharmaceutical Engineering Research Center
      Shanghai, Shanghai Shi, China
  • 2015
    • National Tissue Engineering Research Center of China
      Shanghai, Shanghai Shi, China
    • Chinese Academy of Sciences
      Peping, Beijing, China
  • 2010-2015
    • Shanghai University of Traditional Chinese Medicine
      Shanghai, Shanghai Shi, China
  • 2008-2015
    • Shanghai Jiao Tong University
      • • State Key Laboratory of Medical Genomics
      • • Department of Radiology (Renji)
      • • State Key Laboratory of Metal Matrix Composites
      Shanghai, Shanghai Shi, China
  • 2012
    • Shanghai Institute of Technology
      Shanghai, Shanghai Shi, China
  • 2011
    • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      Shanghai, Shanghai Shi, China
  • 2009
    • University of Paris-Est
      La Haye-Descartes, Centre, France
  • 2001-2006
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2002
    • La Ligue contre le cancer
      Lutetia Parisorum, Île-de-France, France
  • 1996-2002
    • Second Military Medical University, Shanghai
      Shanghai, Shanghai Shi, China