Publications by authors named "Nannan Chen"

59 Publications

Antibacterial Activities of Bacillus amyloliquefaciens DQB-1 Isolated From the Cecum of Dezhou Donkeys.

J Equine Vet Sci 2021 Jul 16;102:103616. Epub 2021 Apr 16.

College of Animal Science and Veterinary Medicine, HeiLongJiang BaYi Agricultural University, Daqing, China. Electronic address:

The microorganisms in the cecum of donkeys share similar functions as those in the rumen of cattle. Transformation of the cecal microenvironment by probiotics plays an important role in the health and growth of donkeys. In order to screen out excellent donkey probiotic preparations, in this study, we isolated an antibacterial strain of Bacillus amyloliquefaciens (designated as DQB-1) from the cecum of Dezhou donkey. The strain was assessed in terms of antibacterial activity, antibacterial substance analysis, and stability. The results show that, the Bacillus amyloliquefaciens DQB-1 exhibited protease production activity and can significantly inhibit the growth of bacterial and fungal pathogens. The strongest antibacterial substance would be obtained after 24 hours of growth. The most suitable storage temperature for antibacterial extracts is -20 °C. The antibacterial substance produced by Bacillus amyloliquefaciens DQB-1 isolated from donkeys has strong antibacterial activity, protease-producing activity and good stability. Therefore, it can be developed as a probiotic preparation for preventing infectious diseases in donkey farms.
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http://dx.doi.org/10.1016/j.jevs.2021.103616DOI Listing
July 2021

Bovine viral diarrhea virus NS4B protein interacts with 2CARD of MDA5 domain and negatively regulates the RLR-mediated IFN-β production.

Virus Res 2021 Jun 18;302:198471. Epub 2021 Jun 18.

College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China; Heilongjiang Provincial Technology Innovation Center for Bovine Disease Control and Prevention, Daqing 163319, China; Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, Daqing 163319, China; Heilongjiang Province Cultivating Collaborative Innovation Center for The Beidahuang Modern Agricultural Industry Technology, Daqing 163319, China. Electronic address:

Bovine viral diarrhea virus (BVDV) is an important member of the family Flaviviridae and often causes immunosuppression. Previous studies have suggested that BVDV envelope protein E and the nonstructural autoprotease N can inhibit host innate immune responses. Herein, we found that BVDV NS4B, as a nonstructural protein necessary for replication, is involved in antagonizing the main RNA virus sensing pathway. Overexpression of BVDV NS4B protein significantly inhibited Sendai virus (SeV)-induced interferon-β promoter activity, IFN-β mRNA and IFN regulatory factor 3 (IRF3) phosphorylation levels. We also discovered that BVDV NS4B protein significantly inhibited RIG-I like receptor (RLRs)-mediated interferon-β (IFN-β) promoter activity and endogenous MDA5 mRNA levels. In addition, the BVDV NS4B protein directly interacts with N-terminal CARDs of MDA5, and co-localized with MDA5 or MDA5-2CARD in the cytoplasm. In summary, the results of this study indicate that the BVDV NS4B protein acts as an interferon-β antagonist through inhibiting the MDA5-mediated signal transduction pathway. Our study provides an in-depth understanding of the molecular mechanisms of BVDV evading the host's natural immune response.
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http://dx.doi.org/10.1016/j.virusres.2021.198471DOI Listing
June 2021

SYNCRIP facilitates porcine parvovirus viral DNA replication through the alternative splicing of NS1 mRNA to promote NS2 mRNA formation.

Vet Res 2021 May 25;52(1):73. Epub 2021 May 25.

College of Veterinary Medicine, Northwest A&F University, Yangling, China.

Porcine Parvovirus (PPV), a pathogen causing porcine reproductive disorders, encodes two capsid proteins (VP1 and VP2) and three nonstructural proteins (NS1, NS2 and SAT) in infected cells. The PPV NS2 mRNA is from NS1 mRNA after alternative splicing, yet the corresponding mechanism is unclear. In this study, we identified a PPV NS1 mRNA binding protein SYNCRIP, which belongs to the hnRNP family and has been identified to be involved in host pre-mRNA splicing by RNA-pulldown and mass spectrometry approaches. SYNCRIP was found to be significantly up-regulated by PPV infection in vivo and in vitro. We confirmed that it directly interacts with PPV NS1 mRNA and is co-localized at the cytoplasm in PPV-infected cells. Overexpression of SYNCRIP significantly reduced the NS1 mRNA and protein levels, whereas deletion of SYNCRIP significantly reduced NS2 mRNA and protein levels and the ratio of NS2 to NS1, and further impaired replication of the PPV. Furthermore, we found that SYNCRIP was able to bind the 3'-terminal site of NS1 mRNA to promote the cleavage of NS1 mRNA into NS2 mRNA. Taken together, the results presented here demonstrate that SYNCRIP is a critical molecule in the alternative splicing process of PPV mRNA, while revealing a novel function for this protein and providing a potential target of antiviral intervention for the control of porcine parvovirus disease.
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http://dx.doi.org/10.1186/s13567-021-00938-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152309PMC
May 2021

Discovery of a covalent inhibitor of heat shock protein 90 with antitumor activity that blocks the co-chaperone binding via C-terminal modification.

Cell Chem Biol 2021 Apr 26. Epub 2021 Apr 26.

State Key Laboratory of Natural Medicines, and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Heat shock protein (Hsp90), a critical molecular chaperone that regulates the maturation of a large number of oncogenic client proteins, plays an essential role in the growth of neoplastic cells. Herein, DDO-6600 is identified to covalent modification of Cys598 on Hsp90 from in silico study and is verified by a series of biological assays. We demonstrated that DDO-6600 covalently bound to Cys598 on the Hsp90 C terminus and exhibited antiproliferative activities against multiple tumor cells without inhibiting ATPase activity. Further studies showed that DDO-6600 disrupted the interaction between Hsp90 and Cdc37, which induced the degradation of kinase client proteins in multiple tumor cell lines, promoted apoptosis, and inhibited cell motility. Our findings offer mechanic insights into the covalent modification of Hsp90 and provide an alternative strategy for the development of Hsp90 covalent regulators or chemical probes to explore the therapeutical potential of Hsp90.
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http://dx.doi.org/10.1016/j.chembiol.2021.03.016DOI Listing
April 2021

Comparison of the bacteriostatic effects of quaternary ammonium compounds and their combinations on a dairy farm environment and the microbial contamination of dairy products.

Can J Vet Res 2021 Apr;85(2):151-155

College of Animal Science and Veterinary Medicine, Heilongjiang Province Cultivating Collaborative Innovation Center for The Beidahuang Modern Agricultural Industry Technology, Heilongjiang BaYi Agricultural University, Daqing 163319, China (Nannan Chen, Shanshan Liu, Yu Liu, Tongtong Bai, Li Wang, Shan Yue, Chenhua Wu, Wenjing Huang, Li Gao, Jinlei Fu, Siyu Liu, Tong Zhao, Zhanbo Zhu); Branch of Animal Husbandry and Veterinary of Heilongjiang Academy of Agricultural Sciences, Qiqihar 161006, China (Nannan Chen); Harbin Lening Biotechnology, Harbin 150000, China (Yu Liu); College of Chemistry and Chemical Engineering, Key Laboratory of Fine Chemicals of College of Heilongjiang Province, Qiqihar University, Qiqihar 161006, China (Lihua Jia); Agricultural International Cooperation and Exchange Station of Shanxi Province, Taiyuan, 030000, China (Juan Li); Harbin Examining and Inspection Center for Agricultural Products Safety and Quality, Harbin 150028, China (Yuntao Zhang).

Disinfection is key for controlling microbial contamination and ensuring the safe production of milk and dairy products. In this study, we developed a new disinfection method using quaternary ammonium surfactant N-dodecyl-2-(pyridin-1-yl) acetamide chloride as the main component to form a bactericidal complex with either chlorhexidine acetate or glutaraldehyde, and we evaluated the bactericidal effects, safety, and clinical application value of the compound disinfectants. An acute oral toxicity assay in mice showed an LD > 5000 mg/kg body weight without abnormality in pathological tissue sections. Comparison with commercially available products also showed that they have outstanding bactericidal effects. Clinical trials proved that the compound disinfectants have excellent bactericidal effects on the air and ground of the dairy farm and on the skin of cattle, especially in a dairy farm environment. Our findings confirm that the new compound disinfectants have excellent bactericidal performance and are safe to use as disinfectants to prevent mastitis and contamination of the cattle farm environment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995534PMC
April 2021

Controllable synthesis of Cu-Ni-M (M = S, P and Se) hybrid nanoarrays for efficient water splitting reaction.

Dalton Trans 2021 Mar;50(8):2964-2972

School of Science, North University of China, Taiyuan 030051, People's Republic of China.

Electrochemical water splitting has become one of the state of the art approaches to generate hydrogen. It is important to exploit relatively low toxicity, low cost and environmentally friendly water splitting electrocatalysts. A series of Cu-Ni-M (M = S, P and Se) materials were firstly in situ grown on Ni foam and these materials showed excellent water splitting activity. The Cu-Ni-S material shows excellent oxygen evolution reaction performance (200 [email protected] mA cm-2) and the Cu-Ni-P sample shows an effective hydrogen evolution reaction performance (52 [email protected] mA cm-2). When the Cu-Ni-S and Cu-Ni-P materials were assembled into a two-electrode system, the Cu-Ni-S/NF//Cu-Ni-P/NF electrode pairs display superior water splitting activity (1.50 [email protected] mA cm-2), which is one of the best electrocatalytic activities reported so far. The experimental analysis demonstrates that the excellent performance of the Cu-Ni-S/NF and Cu-Ni-P/NF materials is attributed to the rapid electron transfer rate, increased electrocatalytically active area, more exposure to active sites and the superior synergistic catalytic factor of Ni2+ and Cu2+. It was found that amorphous oxides were in situ generated on the outside surface of the catalyst through the analysis of the catalyst after the reaction, and they were the real electrocatalytically active centers. Density functional theory demonstrates that the in situ generated Cu-doped NiOOH shows the optimal water adsorption energy compared with NiOOH. This work offers novel views for the design of relatively low toxicity, stable and inexpensive water splitting electrocatalysts.
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http://dx.doi.org/10.1039/d0dt04179cDOI Listing
March 2021

Acetylation-dependent glutamate receptor GluR signalosome formation for STAT3 activation in both transcriptional and metabolism regulation.

Cell Death Discov 2021 Jan 14;7(1):11. Epub 2021 Jan 14.

Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, 215123, Suzhou, Jiangsu, China.

Besides their original regulating roles in the brain, spinal cord, retina, and peripheral nervous system for mediating fast excitatory synaptic transmission, glutamate receptors consisting of metabotropic glutamate receptors (GluRs) and ionotropic glutamate receptors (iGluRs) have emerged to have a critical role in the biology of cancer initiation, progression, and metastasis. However, the precise mechanism underpinning the signal transduction mediated by ligand-bound GluRs is not clearly elucidated. Here, we show that iGluRs, GluR1 and GluR2, are acetylated by acetyltransferase CREB-binding protein upon glutamate stimulation of cells, and are targeted by lysyl oxidase-like 2 for deacetylation. Acetylated GluR1/2 recruit β-arrestin1/2 and signal transducer and activator of transcription 3 (STAT3) to form a protein complex. Both β-arrestin1/2 and STAT3 are subsequently acetylated and activated. Simultaneously, activated STAT3 acetylated at lysine 685 translocates to mitochondria to upregulate energy metabolism-related gene transcription. Our results reveal that acetylation-dependent formation of GluR1/2-β-arrestin1/2-STAT3 signalosome is critical for glutamate-induced cell proliferation.
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http://dx.doi.org/10.1038/s41420-020-00389-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809112PMC
January 2021

Synthesis of Ethylenediaminetetraacetic Acid Disodium Salt Functionalized Magnetite/Chitosan Nanospheres for the Highly Efficient Removal of Methylene Blue.

J Nanosci Nanotechnol 2021 03;21(3):1694-1702

Co-Innovation Center for Efficient Processing and Utilization of Forest Products, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China.

In this paper, novel Ethylenediaminetetraacetic acid disodium salt (EDTA) functionalized magnetite/ chitosan nanospheres (Fe₃O₄/CS-EDTA) are synthesized by combining solvothermal method and chemical modification, and they are further applied as a kind of adsorbent to eliminate dye of methylene blue (MB) from wastewater. The properties as well as structure exhibited by the fabricated adsorbent are characterized through FTIR, XRD, TG and TEM, together with VSM. The impact exerted by sorption parameters (time of contact, initial dye concentration, temperature, etc.) on the adsorptions were evaluated in batch system. These results demonstrated that our magnetic materials held the adsorption capacity for MB of 256 mg g (pH = 11), and the kinetic model of pseudo-second-order and the Langmuir model could make an effective simulation regarding the adsorption kinetics and isotherm, respectively. Besides, the external magnetic field can assist in easily separating dye adsorbed Fe₃O₄/CS-EDTA from solution for regeneration. The removal efficiency of recycled adsorbents remained above 92% in the 5th adsorption/desorption cycle. These superioritiesmake Fe₃O₄/CS-EDTA a high-efficientmultifunctional adsorbent for removing dyes from wastewater.
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http://dx.doi.org/10.1166/jnn.2021.19032DOI Listing
March 2021

Porcine DNAJB6 promotes PCV2 replication via enhancing the formation of autophagy in host cells.

Vet Res 2020 May 7;51(1):61. Epub 2020 May 7.

College of Veterinary Medicine, Northwest A&F University, Yangling, China.

Hsp40/DnaJ family proteins play important roles in the infection process of various viruses. Porcine DNAJB6 (pDNAJB6) is a major member of this family, but its role in modulating the replication of porcine circovirus type 2 (PCV2) is still unclear. In the present study, pDNAJB6 was found to be significantly upregulated by PCV2 infection, and confirmed to be interacted with PCV2 capsid (Cap) protein and co-localized at both cytoplasm and nucleus in the PCV2-infected cells. Knockout of pDNAJB6 significantly reduced the formation of autophagosomes in PCV2-infected cells or in the cells expressing Cap protein, whereas overexpression of pDNAJB6 showed an opposite effect. In addition, the domain mapping assay showed that the J domain of pDNAJB6 (amino acids (aa) 1-99) and the C terminus of Cap (162-234 aa) were required for the interaction of pDNAJB6 with Cap. Notably, the interaction of pDNAJB6 with Cap was very important to promoting the formation of autophagosomes induced by PCV2 infection or Cap expression and enhancing the replication of PCV2. Taken together, the results presented here show a novel function of pDNAJB6 in regulation of porcine circovirus replication that pDNAJB6 enhances the formation of autophagy to promote viral replication through interacting with viral capsid protein during PCV2 infection.
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http://dx.doi.org/10.1186/s13567-020-00783-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203849PMC
May 2020

Multicompartment occurrence and partitioning of alternative and legacy per- and polyfluoroalkyl substances in an impacted river in China.

Sci Total Environ 2020 Aug 18;729:138753. Epub 2020 Apr 18.

School of Environment, Beijing Normal University, State Key Laboratory of Water Environment Simulation, Beijing 100875, China.

Per- and polyfluoroalkyl substances (PFASs) are emerging global environmental contaminants. Exploring the occurrence and environmental behavior of PFASs in the aquatic environment is a key step in solving global fluorine chemical pollution problems. In this study, surface water, pore water, and sediment were collected from the main tributary and the middle and lower reaches of the Daling River, adjacent to the Fuxin fluorochemical manufacturing facilities in Liaoning Province in China, to elucidate the occurrence and partition behavior of PFASs. The total concentrations of PFASs ranged from 48.4 to 4578 ng/L in the overlying water, from 173 to 9952 ng/L in the pore water, and from 2.16 to 40.3 ng/g dw in the sediment fraction. Generally, perfluorobutanoic acid (PFBA) and perfluorobutane sulfonate (PFBS) were the predominant congeners in the samples, with the mean relative content fractions being almost consistently >40% in the dissolved phase and >25% in the sediment. Hexafluoropropylene oxide dimer acid (HFPO-DA) and chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA) were detected, albeit at low levels. In addition, the detection frequency and the contribution of legacy long-chain PFASs in sediment were higher than those in the overlying water and pore water. Except for perfluorohexane sulfonate (PFHxS), the concentrations of the alternative PFASs in the pore water were higher than in the overlying water. The organic carbon fraction was a more important controlling factor for PFAS sediment levels than cations content. As with legacy long-chain PFASs, HFPO-DA and 6:2 Cl-PFESA tended to partition into the solid phase, whereas short-chain PFASs were readily distributed in the aqueous phase. Such research results will be helpful in modeling the transport and fate of PFASs released by point sources into coastal waters through rivers and in developing effective risk assessment and management strategies for the control of PFAS pollution.
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http://dx.doi.org/10.1016/j.scitotenv.2020.138753DOI Listing
August 2020

PD-1-Mediated PI3K/Akt/mTOR, Caspase 9/Caspase 3 and ERK Pathways Are Involved in Regulating the Apoptosis and Proliferation of CD4 and CD8 T Cells During BVDV Infection .

Front Immunol 2020 17;11:467. Epub 2020 Mar 17.

College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China.

Acute infection of bovine viral diarrhea virus (BVDV) is associated with immune dysfunction and can cause peripheral blood lymphopenia and lymphocyte apoptosis. Our previous study has confirmed that programmed death-1 (PD-1) blockade inhibits peripheral blood lymphocyte (PBL) apoptosis and restores proliferation and anti-viral immune functions of lymphocytes after BVDV infection . However, the immunomodulatory effects of PD-1 pathway on major PBL subsets are unclear and their underlying molecular mechanisms need to be further studied. Therefore, in this study, we examined PD-1 expression in bovine PBL subsets after BVDV infection and analyzed the effects of PD-1 blockade on the apoptosis and proliferation of CD4 and CD8 T cells and expression of PD-1 downstream signaling molecules. The results showed that PD-1 expression was enhanced on CD4 and CD8 T cells, but not on CD21 B cells after cytopathic (CP) BVDV (strain NADL) and non-cytopathic (NCP) BVDV (strain KD) infection and PD-1 blockade significantly reduced the apoptosis of CD4 and CD8 T cells after these two strains infection. Remarkably, PD-1 blockade significantly increased the proliferation of CD4 and CD8 T cells after CP BVDV infection, but only significantly increased the proliferation of CD4 T cells after NCP BVDV infection. In addition, we confirmed that PD-1-mediated PI3K/Akt/mTOR, caspase 9/caspase 3 and ERK pathways are involved in regulating the apoptosis and proliferation of CD4 and CD8 T cells during BVDV infection . Notably, ERK is involved in the regulation mechanism PD-1 mediated only when the cells are infected with CP BVDV. Our findings provide a scientific basis for exploring the molecular mechanism of immune dysfunction caused by acute BVDV infection.
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http://dx.doi.org/10.3389/fimmu.2020.00467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089960PMC
March 2021

A novel porcine parvovirus DNA-launched infectious clone carrying stable double labels as an effective genetic platform.

Vet Microbiol 2020 Jan 6;240:108502. Epub 2019 Nov 6.

College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China. Electronic address:

Porcine parvovirus (PPV) is one of the major pathogens causing reproductive failure of swine. However, its specific pathogenesis has not been fully elucidated. Infectious clone is a powerful tool for further studying the pathogenic mechanism of PPV. In the present study, a PPV infectious clone was constructed, and the clone carries His-tag and Flag-tag double-genetic marker at the end of the ns1 gene 3' terminal and vp1 gene 5' terminal, respectively. The PPV DNA fragment F1 (1-182) in 5' end and the other PPV DNA fragment F2 (4788-5074) in 3' end were synthesized and assembled to the lower copy plasmid to construct pKQLL(F1 + F2), while the PPV DNA genome as a template to amplify carrying tags sequence PPV middle DNA fragment F3 and F4 by introducing Flag and His tags sequence in primers. Subsequently, the fused fragment F3/F4 were cloned into the Stu I/Sna B I sites of pKQLL(F1 + F2) plasmid to assemble the complete full-length PPV DNA recombinant plasmids, named as pD-PPV. The pD-PPV was transfected into PK-15 cells to gain rescued PPV virus, designed as D-PPV. Moreover, D-PPV showed similar replicate capability and pathogenicity comparing to the wild-type parental PPV through in vitro and in vivo studies, and the double labels can effectively indicate the expression and localization of viral proteins. Finally, the rescued D-PPV was found to be a convenient tool for antiviral drug screening. These data indicated that the newly established reverse genetic system for PPV would be a useful tool for further studying the pathogenesis mechanisms of PPV, developing labeled vaccine and screening antiviral drug.
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http://dx.doi.org/10.1016/j.vetmic.2019.108502DOI Listing
January 2020

TERT assists GDF11 to rejuvenate senescent VEGFR2/CD133 cells in elderly patients with myocardial infarction.

Lab Invest 2019 11 10;99(11):1661-1688. Epub 2019 Jul 10.

Department of Cardiology, Yangpu Hospital, Tongji University School of Medicine, 450 Tengyue Road, 200090, Shanghai, PR China.

Growth differentiation factor 11 (GDF11) is a transforming growth factor β superfamily member with a controversial role in rejuvenating old stem cells after acute injury in the elderly population. This study aimed to evaluate the effects of telomerase reverse transcriptase (TERT) on GDF11-mediated rejuvenation of senescent late-outgrowth endothelial progenitor cells (EPCs), defined as VEGFR2/CD133 cells, in elderly patients with acute myocardial infarction (AMI). We compared the quantity and capabilities of VEGFR2/CD133 cells from old (>60 years), middle-aged (45-60 years), and young (<45 years) AMI patients. The decline in circulating count and survival of VEGFR2/CD133 cells with age was accompanied by decrease in their TERT and GDF11 expression levels in patients with AMI. Further, upregulation of TERT could trigger GDF11-mediated rejuvenation of old VEGFR2/CD133 cells by renewing their survival and angiogenic abilities through activation of canonical (Smad2/3) and noncanonical (eNOS) signaling pathways. Depletion of GDF11 or TERT caused senescence of young VEGFR2/CD133 cells leading to impaired vascular function and angiogenesis in vitro and in vivo, whereas adTERT and rhGDF11 rescued this senescence. TERT cooperates with GDF11 to enhance regenerative capabilities of old VEGFR2/CD133 cells. When combined with TERT, GDF11 may represent a potential therapeutic target for the treatment of elderly patients with MI.
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http://dx.doi.org/10.1038/s41374-019-0290-1DOI Listing
November 2019

Highly efficient regio-selective ring-opening nucleophilic fluorination of aziridines and azetidines: access to β- or γ-fluorinated amino acid derivatives.

Org Biomol Chem 2019 04;17(15):3797-3804

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong 510006, China.

Herein, we have presented a facile and efficient method of ring-opening nucleophilic fluorination of aziridines, affording highly regio-selective β-fluorinated amines. Firstly, the example of ring-opening hydrofluorination of azetidines was reported. Then, the Olah's reagent also provided a promising method for the construction of enantioenriched β-fluoro-α-amino acid derivatives, which could be used for the preparation of peptide-based bioactive molecules.
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http://dx.doi.org/10.1039/c9ob00172gDOI Listing
April 2019

Controllable assembly of a novel cationic gemini surfactant containing a naphthalene and amide spacer with β-cyclodextrin.

Soft Matter 2019 Apr;15(15):3198-3207

College of Chemistry and Chemical Engineering, Key Laboratory of Fine Chemicals of College of Heilongjiang Province, Qiqihar University, Qiqihar 161006, China.

A novel cationic gemini surfactant (C12NDDA) with a spacer containing naphthalene and amides was successfully synthesized. The assembly of C12NDDA with β-cyclodextrin (β-CD) was investigated using various techniques including transmission electron microscopy, proton nuclear magnetic resonance (1H NMR), and scanning electron microscopy. Tuning the C12NDDA concentration and the C12NDDA/β-CD molar ratio allowed the production of different assembled aggregate morphologies such as micelles, vesicles, nanowires, nanorods, and hydrogels. Investigation of the inclusion mechanisms of C12NDDA and β-CD by 1H NMR revealed that hydrophobic interactions, hydrogen bonding, π-π stacking, and electrostatic forces play key roles in the assembly process. The antimicrobial activities of the C12NDDA/xβ-CD (x = 0-4) inclusion complexes were tested against Gram-negative bacteria (Escherichia coli and Salmonella) and Gram-positive bacteria (Staphylococcus aureus and Streptococcus), and very low minimum inhibitory concentrations of 0.078-0.31 μg mL-1 were observed. Thus, this newly synthesized gemini surfactant and its inclusion complexes exhibit potential as superior broad-spectrum disinfectants for various biomedical and biotechnological applications.
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http://dx.doi.org/10.1039/c9sm00172gDOI Listing
April 2019

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones.

J Vis Exp 2019 02 7(144). Epub 2019 Feb 7.

School of Pharmaceutical Sciences, Sun Yat-sen University;

Bispirocyclic scaffolds are one of the important structural subunits in many natural products that exhibit diverse and attractive biological activities. Recently, we have developed an efficient organocatalytic strategy, which provides facile access to a variety of enantiomerically enriched bispiro[γ-butyrolactone-pyrrolidin-4,4'-pyrazolone] skeletons. In this paper, we demonstrate a detailed protocol for the asymmetric synthesis of drug-like bispirocyclic compounds with two spirocyclic carbon centers via an organocatyltic 1,3-dipolar cycloaddition reaction. Spirocyclization synthons α-imino γ-lactones and alkylidene pyrazolones are prepared first, which are then subjected to a cycloaddition reaction in the presence of a bifunctional squaramide organocatalyst to afford the desired bispirocycles in high yields and excellent stereoselectivities. Chiral high-performance liquid chromatography (HPLC) is carried out to determine the enantiomeric purity of the products, and the d.r. value is examined by proton nuclear magnetic resonance (H NMR). The absolute configuration of the product is assigned according to an X-ray crystallographic analysis. This synthetic strategy allows scientists to prepare a diversity of bispirocyclic scaffolds in high yields and excellent diastereo- and enantioselectivities.
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http://dx.doi.org/10.3791/59155DOI Listing
February 2019

Suppression of GABAergic neurons through D2-like receptor secures efficient conditioning in aversive olfactory learning.

Proc Natl Acad Sci U S A 2019 03 22;116(11):5118-5125. Epub 2019 Feb 22.

Institute of Biophysics, State Key Laboratory of Brain and Cognitive Science, Chinese Academy of Sciences, 100101 Beijing, China;

The GABAergic system serves as a vital negative modulator in cognitive functions, such as learning and memory, while the mechanisms governing this inhibitory system remain to be elucidated. In , the GABAergic anterior paired lateral (APL) neurons mediate a negative feedback essential for odor discrimination; however, their activity is suppressed by learning via unknown mechanisms. In aversive olfactory learning, a group of dopaminergic (DA) neurons is activated on electric shock (ES) and modulates the Kenyon cells (KCs) in the mushroom body, the center of olfactory learning. Here we find that the same group of DA neurons also form functional synaptic connections with the APL neurons, thereby emitting a suppressive signal to the latter through dopamine 2-like receptor (DD2R). Knockdown of either DD2R or its downstream molecules in the APL neurons results in impaired olfactory learning at the behavioral level. Results obtained from in vivo functional imaging experiments indicate that this DD2R-dependent DA-to-APL suppression occurs during odor-ES conditioning and discharges the GABAergic inhibition on the KCs specific to the conditioned odor. Moreover, the decrease in odor response of the APL neurons persists to the postconditioning phase, and this change is also absent in DD2R knockdown flies. Taken together, our findings show that DA-to-GABA suppression is essential for restraining the GABAergic inhibition during conditioning, as well as for inducing synaptic modification in this learning circuit. Such circuit mechanisms may play conserved roles in associative learning across species.
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http://dx.doi.org/10.1073/pnas.1812342116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421402PMC
March 2019

Manipulating Depletion Region of Aqueous-Processed Nanocrystals Solar Cells with Widened Fermi Level Offset.

Small 2018 Nov 11;14(47):e1803072. Epub 2018 Oct 11.

College of Chemistry, National and Local United Engineering Laboratory for Power Batteries, Northeast Normal University, 5268, Renmin Street, Changchun, 130024, P. R. China.

Water soluble nanocrystals (NCs) are promising materials in aqueous-processed solar cells because of their high extinction coefficient, low-cost, and favorable photoelectric characteristics. However, the power conversion efficiency (PCE) of the present aqueous-processed NC solar cells is restricted by the short depletion region of the active layer and limited Fermi level offset between NCs and the electron transport layer. Herein, these issues are effectively addressed by preparing Cd Zn Te NCs capped with 2-aminoethanethiol hydrochloride. The introduction of Zn into CdTe NCs widens the Fermi level offset from 0.68 to 0.74 eV, lengthens the depletion region from 130 to 137 nm, and hence brings obvious improvement in the open circuit voltage (V ) and fill factor. Especially, the depletion region is successfully tuned from 137 to 171 nm, and even lengthened to a record thickness of 200 nm based on aqueous-processed solar cells. As a result, a champion thickness ratio (74%) of depletion region to active layer (200/270 nm) is achieved. A champion PCE of 5.96% and short-circuit current (J ) of 21.2 mA cm are achieved among aqueous-processed NC solar cells. This work provides a simple way to prepare polynary NCs and highlights a prospective method to develop more efficient and cost-effective solution-processed environment friendly solar cells.
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http://dx.doi.org/10.1002/smll.201803072DOI Listing
November 2018

Catalytic Asymmetric [4 + 3] Annulation of C, N-Cyclic Azomethine Imines with Copper Allenylidenes.

Org Lett 2018 10 5;20(20):6506-6510. Epub 2018 Oct 5.

School of Pharmaceutical Sciences , Sun Yat-Sen University , Guangzhou , Guangdong 510006 , China.

The first asymmetric decarboxylative [4 + 3] annulation of propargylic carbamates with C, N-cyclic azomethine imines has been developed successfully by a copper- N-heterocyclic carbine system. This strategy led to a series of optically active isoquinoline-fused triazepine derivatives in good yields and with excellent enantio- and diastereoselectivities. Remarkably, Cu-allenylidene intermediates play a crucial role in this transformation.
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http://dx.doi.org/10.1021/acs.orglett.8b02828DOI Listing
October 2018

Multiple Silver Nanoparticles Anchored Hollow Mesoporous Silica Nanospheres by Polyacrylic Acid Aggregate Templating Approach for Catalytic Reduction of -Nitrophenol.

J Nanosci Nanotechnol 2018 12;18(12):8307-8312

Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China.

Anchoring metal cores inside porous shells can endow metal catalyst with high selectivity and stability. Herein, multiple silver nanoparticles were successfully anchored in hollow mesoporous silica nanospheres ([email protected]) through a facile one-pot method. Polyacrylic acid aggregates self-assembled in water/ethanol solvent were used as core templates and Ag nanoparticles captors, and hexadecyl trimethoxysilane (C16TMS) was used as the pore-making agent. The hollow cavity, encapsulated multiple Ag nanoparticles, and mesoporous silica shell of the [email protected] were confirmed by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), and nitrogen sorption analysis. Just as expected, Ag nanoparticles (2-5 nm) were encapsulated in the cavity of hollow mesoporous silica nanospheres with the size of about 200 nm. The fabricated [email protected] showed excellent performance for catalytic reduction of p-nitrophenol (4-NP). Also, catalytic activity of the [email protected] for 4-NP reduction was increased with the addition amount of the pore-making agents and surface areas. The superior catalytic performance was attributed to the unique structural features of [email protected] architecture, in which the mesoporous shell provided readily accessible pathway for fast transport of reactants to the encapsulated Ag nanoparticles.
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http://dx.doi.org/10.1166/jnn.2018.16412DOI Listing
December 2018

Ionic Strength and pH Responsive Permeability of Soy Glycinin Microcapsules.

Langmuir 2018 08 6;34(33):9711-9718. Epub 2018 Aug 6.

Department of Nutrition and Food Science, University of Maryland , College Park , Maryland 20742 , United States.

Recently, hollow protein microcapsules have been made simply by heating the microphase separated soy glycinin microdomains. However, the properties (e.g., mechanical properties and permeability) that relate to the application of these microcapsules are unknown. In this study, the permeability of the soy glycinin microcapsules was investigated by confocal laser scanning microscopy (CLSM), as influenced by ionic strength and pH using fluorescein isothiocyanate-dextran (FITC-dextran). The glycinin microcapsules kept the integrity between pH 1 and 11.5, swelled when pH was below 3 or above pH 11, dissociated at pH above 11.5 and deswelled slightly at pH 1. When the pH increased above 11, the permeability of the microcapsule significantly increased. Remarkably, when the pH was below the isoelectric point of glycinin (≈pH 5), FITC-dextran spontaneously accumulated inside the microcapsule with a significantly higher concentration than that in bulk solution, as evidenced by the strong intensity increase of fluorescence. This unique feature significantly increased the loading amount of FITC-dextran. The permeability of microcapsules was also increased by adding salt but less significant than by adjusting pH. The surface of the microcapsules became coarser when the permeability increased, which was revealed by scanning electron microscopy. These results show that soy glycinin has a great potential to be used as a wall material to fabricate hollow microcapsules that could find applications in biomedicine and food industry.
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http://dx.doi.org/10.1021/acs.langmuir.8b01559DOI Listing
August 2018

Label-free sensitive luminescence biosensor for immunoglobulin G based on AgAu ethisterone cluster-estrogen receptor α aggregation and graphene.

Talanta 2018 Aug 27;185:243-248. Epub 2018 Mar 27.

MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China.

A specific and label-free "on-off-on" luminescence biosensor based on a novel heterometallic cluster [AgAu(ethisterone)]-estrogen receptor α (AgAuEth-ERα) aggregation utilizing graphene oxide (GO) as a quencher to lead a small background signal was firstly constructed to detect immunoglobulin G (IgG) with a simple process and high selectivity. The efficient photoluminescent (PL) AgAuEth-ERα aggregation is strongly quenched by GO. In the presence of IgG, the PL of this system will be restored, and perceivable by human eyes under UV lamp excitation (365 nm). The quenching mechanism of GO on AgAuEth-ERα and enhancement mechanism of IgG on AgAuEth-ERα-GO were investigated in detail. Under the optimum conditions, the biosensor for high sensitive IgG detection expressed a wider linear range of 0.0078-10 ng/mL and a lower detection limit of 0.65 pg/mL with good stability and repeatability, which provided a new approach for label-free IgG detection.
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http://dx.doi.org/10.1016/j.talanta.2018.03.075DOI Listing
August 2018

Facile fabrication of silver nanoparticles deposited cellulose microfiber nanocomposites for catalytic application.

J Colloid Interface Sci 2018 Sep 11;526:194-200. Epub 2018 Apr 11.

Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China. Electronic address:

In this study, we have prepared silver nanoparticles deposited cellulose microfibers (Ag-CMFs) with excellent catalytic property. The cellulose microfibers with a mean diameter of approximately 270 nm are regenerated by deacetylation of cellulose acetate microfibers. Silver nanoparticles are deposited onto the surface of the cellulose microfibers by a simple wet reduction of silver precursor using glucose as reducing agent. The morphology, thermal stability and catalytic activities of the samples have been investigated by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG), and UV-vis spectrophotometer. The average size of Ag nanoparticles deposited on the fibers is approximately 10 ± 5 nm, and the deposition of the Ag nanoparticles does not change the morphology of the cellulose microfibers. The obtained Ag-CMFs exhibit excellent catalytic activity and reusable character for the reduction of p-nitrophenol by sodium borohydride. Therefore, the Ag-CMFs prepared by the facile method is expected to be an effective and promising catalytic material.
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http://dx.doi.org/10.1016/j.jcis.2018.04.045DOI Listing
September 2018

Spatiotemporal distribution and risk assessment of organophosphate esters in sediment from Taihu Lake, China.

Environ Sci Pollut Res Int 2018 May 5;25(14):13787-13795. Epub 2018 Mar 5.

School of Engineering, China Pharmaceutical University, Nanjing, 211198, China.

The occurrence and spatiotemporal distribution of 12 organophosphate esters (OPEs) were investigated in the sediments collected from Taihu Lake. Compared to the same lake in 2012 (3.4-14 ng/g dw), the concentrations of ∑12 OPEs in sediments ranged from 10.76 to 335.37 ng/g dw and from 8.06 to 425.39 ng/g dw in 2015 and in 2016, respectively, indicating that the OPEs levels in Taihu Lake have aggravated, recently. TEHP was the most abundant compound of the OPEs, which suggested that TEHP was the most widely used around Taihu Lake recently. The positive correlations between some of individual OPEs and the principal components analysis suggested the same potential sources for them. The strong positive correlation between ∑BPs and TOC content indicated that TOC content was one of the factors affected the distribution of ∑OPEs in the sediment. Risk quotient (RQ) for OPEs showed no high eco-toxicity risk in sediment for aquatic organisms.
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http://dx.doi.org/10.1007/s11356-018-1434-3DOI Listing
May 2018

TBX2 over-expression promotes nasopharyngeal cancer cell proliferation and invasion.

Oncotarget 2017 Aug 13;8(32):52699-52707. Epub 2017 Apr 13.

Institute of Neuroscience, Soochow University, Suzhou, China.

TBX2 is a member of the T box transcription factor family. Its expression and potential biological functions in nasopharyngeal cancer (NPC) cells are studied here. We showed that TBX2 mRNA and protein expression was significantly elevated in multiple human NPC tissues, as compared with that in adjacent normal tissues. Knockdown of TBX2 by targeted-siRNA significantly inhibited proliferation and invasion of NPC cells (CNE-1 and HONE-1 lines). Meanwhile, TBX2 knockdown also induced G1-phase cell cycle arrest. At the molecular level, we discovered that expressions of several tumor suppressor genes, including , and , were increased dramatically after TBX2 knockdown in above NPC cells. Collectively, our results imply that TBX2 over-expression promotes NPC cell proliferation and invasion, possibly via silencing several key tumor suppressor genes.
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http://dx.doi.org/10.18632/oncotarget.17084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5581062PMC
August 2017

Magnetic separable chitosan microcapsules decorated with silver nanoparticles for catalytic reduction of 4-nitrophenol.

J Colloid Interface Sci 2017 Dec 5;507:353-359. Epub 2017 Aug 5.

Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China. Electronic address:

In the work, we have synthesized silver (Ag) nanoparticles deposited chitosan (CS) microcapsules with magnetic multiple FeO cores (denoted as FeO/CS-Ag) as efficient catalysts for the reduction of 4-nitrophenol. The FeO/CS-Ag catalysts are prepared by coating hydrophobic FeO nanoparticles with chitosan via a multiple emulsion-chemical crosslinking method and following in situ deposition of Ag nanoparticles onto the surfaces. The morphology and composition of the FeO/CS-Ag microcapsules are characterized by Fourier transform infrared (FT-IR) spectra, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy. Moreover, the catalytic activity of the FeO/CS-Ag catalyst was investigated, which shows a conversion efficiency as high as 98% within 15min for the reduction of p-nitrophenol to p-aminophenol. At the same time, the recovered FeO/CS-Ag catalyst with an external magnet can retain good activity after 10 cycles. These results indicate that the multiple emulsion-chemical crosslinking method is an efficient and simple way for the preparation of magnetic separable chitosan microcapsules, and the fabricated FeO/CS-Ag is a promising catalytic material with excellent catalytic activity and convenient recovery ability.
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http://dx.doi.org/10.1016/j.jcis.2017.08.014DOI Listing
December 2017

Hierarchical Hybrids Integrated by Dual Polypyrrole-Based Porous Carbons for Enhanced Capacitive Performance.

Chemistry 2017 Sep 5;23(54):13474-13481. Epub 2017 Sep 5.

School of Chemical Engineering and Technology, Xi'an Jiaotong University, Xi'an, 710049, P.R. China.

Architectural design of nitrogenous polymer-based carbons represents a facile and efficient strategy to improve performance because of their morphological diversity, tailorability, and N-containing structure. In this research, 0D and 1D forms of polypyrrole-derived porous carbons (A-PCS and A-PCT, respectively) are first integrated into nitrogen-doped hierarchically porous A-PCS/PCT hybrids by applying an easy multistep method. This integration, along with chemical activation, prevents serious agglomeration of carbon particles or tubes and creates a connected porous network structure, leading to improved textural properties (high surface area of 1684 m  g , high pore volume of 1.57 cm  g , and hierarchical porosity). Thus, A-PCS/PCT hybrids in a three-electrode setup reach high specific capacitances of 224 and 206 F g at 1 and 20 A g , respectively, with high rate capability (92 % capacitance retention). A symmetrical supercapacitor with A-PCS/PCT electrodes presents the highest power and energy densities of 12.6 kW kg and 8.58 Wh kg , respectively, and exceptional cycling life and stability with 92.4 % retention for up to 20 000 cycles. This study on conductive polymer-based hybrid materials may guide the design of architectures with new structures for applications in energy storage and conversion technologies.
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http://dx.doi.org/10.1002/chem.201702544DOI Listing
September 2017

Extragastrointestinal stromal tumor of the abdominal subcutaneous tissue: Report of a very rare case at an unusual site.

J Int Med Res 2017 Jun 28;45(3):1273-1278. Epub 2017 May 28.

Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Extragastrointestinal stromal tumors (EGISTs) are rare tumors that arise outside the digestive tract. We report a case of an EGIST arising in the subcutaneous tissue of the abdominal wall, which at this site can often be misdiagnosed as dermatofibrosarcoma protuberans. The tumor was surgically resected from a 72-year-old male Chinese Han patient, and pathological examination revealed spindle-shaped tumor cells with eosinophilic cytoplasm and an oval nucleus. Immunohistochemically, the tumor cells showed strong cytoplasmic positivity for CD34, c-KIT (CD117), and DOG1. Tests for activating mutations of GISTs showed that the tumor cells carried an in-frame deletion (NP_000213.1:p.Lys550_Gln556del) in exon 11 of c-KIT (CD117). Thus, an EGIST should be considered in patients with abdominal subcutaneous tumors with an epithelioid, spindle-shaped, or mixed morphology. Immunohistochemistry of c-KIT (CD117) and DOG1 and genetic testing for activating mutations are recommended to aid in the differential diagnosis of subcutaneous tumors. In short, although EGISTs are rare in the abdominal subcutaneous tissue, pathologists must be aware of their possibility.
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http://dx.doi.org/10.1177/0300060517706577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536401PMC
June 2017

Exploiting Salt Induced Microphase Separation To Form Soy Protein Microcapsules or Microgels in Aqueous Solution.

Biomacromolecules 2017 Jul 2;18(7):2064-2072. Epub 2017 Jun 2.

IMMM UMR-CNRS 6283, Polymères, Colloïdes et Interfaces, LUNAM Université du Maine , 72085 Le Mans cedex 9, France.

Self-assembly of native glycinin at room temperature was investigated as a function of the pH and the NaCl concentration. Microphase separation leading to the formation of dense protein microdomains was observed by confocal laser scanning microscopy. Depending on the conditions, the microdomains coalesced into a continuous protein rich phase or associated into large clusters. Addition of β-conglycinin inhibited phase separation and reduced the pH range in which it occurred. Microdomains of glycinin that were formed in the presence of 0.1 M NaCl transformed into hollow stable cross-linked microcapsules when heated above 60 °C with diameters between 3 and 30 μm depending on the protein concentration and a shell thickness between 1.0 and 1.4 μm. The microcapsules were stable to dilution in salt free water, whereas microdomains formed at room temperature redispersed. Microdomains formed in mixtures with β-conglycinin did not transform into microcapsules, but they became stable cross-linked homogeneous microgels.
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http://dx.doi.org/10.1021/acs.biomac.7b00393DOI Listing
July 2017

HIF-2α and Oct4 have synergistic effects on survival and myocardial repair of very small embryonic-like mesenchymal stem cells in infarcted hearts.

Cell Death Dis 2017 01 12;8(1):e2548. Epub 2017 Jan 12.

Central Laboratory, Yangpu Hospital, Tongji Univercity School of Medicine, 450 Tengyue Rd, Shanghai 200090, China.

Poor cell survival and limited functional benefits have restricted mesenchymal stem cell (MSC) efficacy for treating myocardial infarction (MI), suggesting that a better understanding of stem cell biology is needed. The transcription factor HIF-2α is an essential regulator of the transcriptional response to hypoxia, which can interact with embryonic stem cells (ESCs) transcription factor Oct4 and modulate its signaling. Here, we obtained very small embryonic-like mesenchymal stem cells (vselMSCs) from MI patients, which possessed the very small embryonic-like stem cells' (VSELs) morphology as well as ESCs' pluripotency. Using microarray analysis, we compared HIF-2α-regulated gene profiles in vselMSCs with ESC profiles and determined that HIF-2α coexpressed Oct4 in vselMSCs similarly to ESCs. However, this coexpression was absent in unpurified MSCs (uMSCs). Under hypoxic condition, vselMSCs exhibited stronger survival, proliferation and differentiation than uMSCs. Transplantation of vselMSCs caused greater improvement in cardiac function and heart remodeling in the infarcted rats. We further demonstrated that HIF-2α and Oct4 jointly regulate their relative downstream gene expressions, including Bcl2 and Survivin; the important pluripotent markers Nanog, Klf4, and Sox2; and Ang-1, bFGF, and VEGF, promoting angiogenesis and engraftment. Importantly, these effects were generally magnified by upregulation of HIF-2α and Oct4 induced by HIF-2α or Oct4 overexpression, and the greatest improvements were elicited after co-overexpressing HIF-2α and Oct4; overexpressing one transcription factor while silencing the other canceled this increase, and HIF-2α or Oct4 silencing abolished these effects. Together, these findings demonstrated that HIF-2α in vselMSCs cooperated with Oct4 in survival and function. The identification of the cooperation between HIF-2α and Oct4 will lead to deeper characterization of the downstream targets of this interaction in vselMSCs and will have novel pathophysiological implications for the repair of infarcted myocardium.
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http://dx.doi.org/10.1038/cddis.2016.480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386383PMC
January 2017