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1.
J Org Chem ; 85(10): 6252-6260, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32298579

RESUMO

A one-pot synthesis of 1,3-diyne-tethered trifluoromethylcyclopropanes starting from 2-CF3-3,5-diyne-1-enes and sulfur ylides via a sulfur ylide mediated cyclopropanation and a DBU-mediated epimerization sequence is described in this work. This process is highly diastereoselective with broad substrate scope. Moreover, a series of synthetic transformations based on the diyne moieties were conducted smoothly, affording cyclopropanes featuring trifluoromethyl-substituted all-carbon quaternary centers.

2.
Nat Commun ; 11(1): 403, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964870

RESUMO

Transition metal catalyzed Sonogashira cross-coupling of terminal alkynes with aryl(vinyl) (pseudo)halides has been successfully extended to alkyl halides for the synthesis of functionalized internal alkynes. The direct alkynylation of remote unfunctionalized sp3 carbon by terminal alkynes remains difficult to realize. We report herein an approach to this synthetic challenge by developing two catalytic remote sp3 carbon alkynylation protocols. In the presence of a catalytic amount of Cu(I) salt and a tridentate ligand (tBu3-terpyridine), O-acyloximes derived from cycloalkanones and acyclic ketones are efficiently coupled with terminal alkynes to afford a variety of γ- and δ-alkynyl nitriles and γ-alkynyl ketones, respectively. These reactions proceed through a domino sequence involving copper-catalyzed reductive generation of iminyl radical followed by radical translocation via either ß-scission or 1,5-hydrogen atom transfer (1,5-HAT) and copper-catalyzed alkynylation of the resulting translocated carbon radicals. The protocols are applicable to complex natural products.

3.
Biomed Pharmacother ; 122: 109726, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918283

RESUMO

Salidroside, a natural active ingredient extracted from Rhodiola rosea, has been shown to exert antitumor activity against breast cancer Dong Young et al. [1], colon cancer Sun et al. [2] and bladder cancer Tian et al. [3]. However, the effect of salidroside on apoptosis and autophagy in gastric cancer remains unclear. In our research, we observed the biological effect of salidroside on human gastric cancer AGS cells. Our results demonstrated that salidroside inhibited the growth of AGS cells both in vivo and in vitro and exerted a proapoptotic effect on AGS cells as confirmed by flow cytometry, Hoechst staining and western blot analysis. Additionally, we found that salidroside decreased the phosphorylation of PI3K and Akt and that pretreatment with the PI3K/Akt agonist IGF-1 could weaken the proapoptotic effect of salidroside. Interestingly, the exposure of AGS cells to salidroside induced autophagy as indicated by transmission electron microscopy, mRFP-GFP-LC3 transfection and western blot analysis, suggesting that salidroside promoted autophagy in gastric cancer AGS cells. Furthermore, treatment with the autophagy inhibitor chloroquine enhanced salidroside-induced cell apoptosis, indicating that the autophagy mediated by salidroside may protect AGS cells from death. Additionally, we found that salidroside decreased the level of p-mTOR protein in a concentration-dependent manner and that pretreatment with IGF-1 decreased the expression of autophagy proteins, suggesting that salidroside induced autophagy through the PI3K/Akt/mTOR pathway. The above findings indicate that salidroside inhibited the growth of gastric cancer and induced apoptosis and protective autophagy through the PI3K/Akt/mTOR pathway. In summary, our study provides novel insights regarding the activity of salidroside against gastric cancer and contributes to the clinical application of salidroside combined with autophagy inhibitors as a chemotherapeutic strategy for human gastric cancer.

4.
J Int Med Res ; : 300060519886241, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852296

RESUMO

BACKGROUND: To investigate the association between the CD14 -159C/T polymorphism and ischemic stroke (IS). METHODS: Relevant literature was searched by retrieving EMBASE, Web of Science, Chinese National Knowledge Infrastructure, and PubMed databases. R version 3.33 software was applied to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Seven qualified studies with a total of 2058 IS patients and 2123 controls were included. There was no significant association between the CD14 -159C/T polymorphism and IS risk in the total population (TT vs CC: OR = 0.84, 95% CI = 0.58-1.20; CT vs CC: OR = 0.96, 95% CI = 0.82-1.12; dominant model: OR = 1.02, 95% CI = 0.80-1.30; recessive model: OR = 0.82, 95% CI = 0.57-1.19). Similarly, subgroup analysis according to ethnicity and Hardy-Weinberg equilibrium also found no significant interrelation. CONCLUSION: Our findings suggest that the CD14 -159C/T polymorphism does not contribute to the risk of IS. Well-designed studies with more subjects are required to further validate these results.

5.
Mol Med Rep ; 20(1): 745-754, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180518

RESUMO

The present study aimed to further clarify the genetic mechanisms responsible for the antimicrobial resistance of Serratia marcescens (S. marcescens) using RNA sequencing. Three drug­susceptible S. marcescens strains (named MYQT1, MYQT2, and MYQT3) and three multidrug­resistant S. marcescens strains (named MYQT4, MYQT5, and MYQT6) were isolated from six different patients and subjected to RNA sequencing. Differentially expressed genes (DEGs) between the multidrug­resistant S. marcescens strains and drug­susceptible strains were screened and compared, followed by functional enrichment analysis. In addition, a protein­protein interaction (PPI) network was constructed, and significant modules were extracted from it. Genes enriched in the significant modules were subjected to further enrichment analysis. MYQT3 had very a different expression pattern from MYQT1 and MYQT2, and thus, MYQT3 was excluded from the following analysis. A total of 225 DEGs were identified, of which SMDB11_RS09300 (GTP cyclohydrolase FolE2) was the most significantly upregulated with a log2 FC of 6.4; these DEGs were enriched in different GO terms, including hydrogen sulfide biosynthetic process, sulfur compound transmembrane transporter activity, and ABC transporter complex. Additionally, several genes were identified to be important genes in the PPI network, including SMDB11_RS17755 (upregulated; glutamate synthase large subunit), SMDB11_RS00590 (upregulated; sulfite reductase subunit α), and SMDB11_RS04505 (upregulated; cystathionine ß­synthase). Thus, SMDB11_RS09300, SMDB11_RS17755, SMDB11_RS00590, and SMDB11_RS04505 may play significant roles in the antimicrobial resistance of S. marcescens by participating in folate metabolism or the integrity of cell membranes. However, further experiments are required to clarify these findings.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Serratia marcescens/efeitos dos fármacos , Serratia marcescens/genética , Regulação Bacteriana da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Mapeamento de Interação de Proteínas , Infecções por Serratia/tratamento farmacológico , Infecções por Serratia/microbiologia , Serratia marcescens/metabolismo , Transcriptoma
6.
Nat Commun ; 10(1): 1764, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30992432

RESUMO

Unlike the vast majority of transition metal dichalcogenides which are semiconductors, vanadium disulfide is metallic and conductive. This makes it particularly promising as an electrode material in lithium-ion batteries. However, vanadium disulfide exhibits poor stability due to large Peierls distortion during cycling. Here we report that vanadium disulfide flakes can be rendered stable in the electrochemical environment of a lithium-ion battery by conformally coating them with a ~2.5 nm thick titanium disulfide layer. Density functional theory calculations indicate that the titanium disulfide coating is far less susceptible to Peierls distortion during the lithiation-delithiation process, enabling it to stabilize the underlying vanadium disulfide material. The titanium disulfide coated vanadium disulfide cathode exhibits an operating voltage of ~2 V, high specific capacity (~180 mAh g-1 @200 mA g-1 current density) and rate capability (~70 mAh g-1 @1000 mA g-1), while achieving capacity retention close to 100% after 400 charge-discharge steps.

7.
Org Biomol Chem ; 17(8): 2279-2286, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30724304

RESUMO

Dialkyl azo compounds were found to be effective alkyl radical sources for direct alkyl sulfuration with imidazopyridines using elemental sulfur under metal-free conditions. Iodine, an inexpensive and mild reagent, could promote alkyl sulfuration. A variety of quaternary cyanoalkyl radicals were successfully coupled with elemental sulfur. A subsequent C-H sulfuration of imidazopyridines afforded a diverse array of imidazopyridine derivatives bearing cyanoalkylthio groups. The cyano group could be modified and further underwent condensation with 2-aminothiazole to afford an interesting heterocyclic amide. Control experiments showed that iodine could greatly suppress the self-coupling of cyanoalkyl radicals, thus making the sulfuration proceed smoothly.

8.
Org Lett ; 21(2): 545-548, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30596506

RESUMO

A sulfite-promoted transformation of azoles into N-difluoromethylthioureas through N-difluoromethylation and sulfuration has been developed. In this reaction, inexpensive ethyl bromodifluoroacetate and nontoxic elemental sulfur were used as the difluoromethylation and sulfuration reagents, respectively. A variety of azoles, including benzimidazoles, imidazoles, and triazoles, performed well to afford a broad range of azole thioureas in moderate to good yields.

9.
Inflamm Bowel Dis ; 25(1): 14-26, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30295722

RESUMO

Background: TNF-like cytokine 1A (TL1A) and its functional receptor, death-domain-receptor-3 (DR3), are multifunctional mediators of effector and regulatory immunity. We aimed to evaluate the functional role and therapeutic potential of TL1A/DR3 signaling in Crohn's disease-like ileitis. Methods: Ileitis-prone SAMP1/YitFc (SAMP) and TNFΔARE/+ mice were rendered deficient for DR3 or TL1A by microsatellite marker-assisted backcrossing. Pathological and immunological characteristics were compared between control and knockout mice, and mucosal immunophenotype was analyzed by Nanostring microarray assay. The therapeutic effect of pharmacological TL1A neutralization was also investigated. Results: DR3 deficiency was associated with restoration of a homeostatic mucosal immunostat in SAMP mice through the regulation of several pro- and anti-inflammatory genes. This led to suppression of effector immunity, amelioration of ileitis severity, and compromised ability of either unfractionated CD4+ or CD4+CD45RBhi mucosal lymphocytes to transfer ileitis to severe combined immunodeficient mice recipients. TNF-driven ileitis was also prevented in TNFΔARE/+xDR3-/- mice, in association with decreased expression of the pro-inflammatory cytokines TNF and IFN-γ. In contrast to DR3, TL1A was dispensable for the development of ileitis although it affected the kinetics of inflammation, as TNFΔARE/+xTL1A-/- demonstrated delayed onset of inflammation, whereas administration of a neutralizing, anti-TL1A antibody ameliorated early but not late TNFΔARE/+ ileitis. Conclusion: We found a prominent pro-inflammatory role of DR3 in chronic ileitis, which is only partially mediated via interaction with TL1A, raising the possibility for additional DR3 ligands. Death-domain-receptor-3 appears to be a master regulator of mucosal homeostasis and inflammation and may represent a candidate therapeutic target for chronic inflammatory conditions of the bowel.


Assuntos
Doença de Crohn/complicações , Regulação da Expressão Gênica , Ileíte/prevenção & controle , Inflamação/prevenção & controle , Membro 25 de Receptores de Fatores de Necrose Tumoral/fisiologia , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Animais , Anticorpos Monoclonais/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Ileíte/etiologia , Inflamação/etiologia , Mediadores da Inflamação/metabolismo , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos SCID , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
11.
Gene ; 691: 106-113, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30586604

RESUMO

Myotubularin-related protein 14 (MTMR14) is a member of the myotubularin (MTM)-related protein family and plays a key role in cardiomyopathy and autophagy. However, its potential implication in human cancer is unclear. In this study, we have investigated the expression profile of MTMR14 and its functional impact in liver cancer for the first time. Expression analysis by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry demonstrated that MTMR14 expression is obviously overexpressed in liver cancer, and positively correlated with clinical stage. A loss-of-function study showed that knockdown of MTMR14 promotes cell apoptosis and inhibits cell migration. MTMR14 knockdown also inhibits tumor migration in vivo in liver cancer peritoneal implantation nude mouse model. A molecular mechanistic study by western blot showed that Knockdown MTMR14 causes downregulation of N-cadherin and E-cadherin, and promotes the cleavage and activation of caspase12, caspase9 and caspase3, but excluding caspase8. These results suggest that MTMR14 affects cell migration through N-cadherin and E-cadherin. Additionally, MTMR14 affects cell apoptosis through mitochondrial pathway but not the death receptor pathway. Herein, our results indicate MTMR14 could have an oncogenic role in human liver cancer and thus demonstrates its potential as a target for the diagnosis and/or treatment of liver cancer.


Assuntos
Neoplasias Hepáticas/patologia , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , Regulação para Cima , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Redes Reguladoras de Genes , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Camundongos , Camundongos Nus , Mitocôndrias/metabolismo , Estadiamento de Neoplasias , Transplante de Neoplasias
12.
J Cancer Res Ther ; 14(Supplement): S1163-S1169, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30539864

RESUMO

Aim: The study aimed to evaluate the effect of concurrent computed tomography (CT)-guided percutaneous interstitial implantation of iodine-125 (125I) seeds and chemotherapy on cervical lymph nodes metastasis. Methods: The prospective randomized study included 82 cases with cervical lymph nodes metastasis who were admitted to our hospital from January 2010 to June 2012. All the subjects were randomly divided into the concurrent 125I implantation and chemotherapy group (n = 48) and chemotherapy-only group (n = 34) according to the treatment strategy. The concurrent 125I implantation and chemotherapy group was treated with CT-guided 125I seeds implantation and routine chemotherapy. The routine chemotherapy included paclitaxel and cisplatin. Patients were followed up for 6 months. Results: In the concurrent 125I implantation and chemotherapy group, overall response rate (complete response [CR] + partial response [PR]) was 82.61% and 85.51% at 2 and 6 months posttreatment, respectively. The longest diameter of CR and PR lymph nodes was markedly decreased after treatment (P < 0.05). In the chemotherapy-only group, overall response rate was 22.45% and 10.20% at 2 and 6 months posttreatment, respectively. The number of patients with moderate to severe pain was much less in concurrent 125I implantation and chemotherapy group than that of chemotherapy-only group (4.17% vs. 17.64%; P < 0.05) at 6-month posttreatment. No treatment-related death or severe complication was reported in the two groups. Conclusion: Concurrent CT-guided 125I seeds implantation and chemotherapy is superior to routine chemotherapy in efficacy, safety, and pain relief in patients with cervical lymph nodes metastasis.


Assuntos
Antineoplásicos/uso terapêutico , Braquiterapia/métodos , Radioisótopos do Iodo/administração & dosagem , Linfonodos/patologia , Metástase Linfática/radioterapia , Radioterapia Guiada por Imagem/métodos , Idoso , Quimiorradioterapia/métodos , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/efeitos da radiação , Metástase Linfática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pescoço , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
Angew Chem Int Ed Engl ; 57(40): 13288-13292, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30113116

RESUMO

Reported herein is an unprecedented copper-catalyzed arylation of remote C(sp3 )-H bonds. Stirring a trifluorotoluene solution of either N-fluorocarboxamides or N-fluorosulfonamides and arylboronic acids in the presence of a catalytic amount of copper(II) trifluoroacetylacetonate, 2,2'-bipyridine, and sodium tert-butoxide afforded the γ- and δ-C(sp3 )-H arylated carboxamides and sulfonamides, respectively, in good to high yields. Mechanistic studies indicate that the reaction might proceed through an amidyl radical generation, 1,5-hydrogen atom transfer (HAT), and copper-catalyzed cross-coupling of the resulting carbon radical with arylboronic acids.

14.
J Exp Med ; 215(7): 1929-1945, 2018 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-29941549

RESUMO

A substantial subset of patients with T cell acute lymphoblastic leukemia (T-ALL) develops resistance to steroids and succumbs to their disease. JDP2 encodes a bZIP protein that has been implicated as a T-ALL oncogene from insertional mutagenesis studies in mice, but its role in human T-ALL pathogenesis has remained obscure. Here we show that JDP2 is aberrantly expressed in a subset of T-ALL patients and is associated with poor survival. JDP2 is required for T-ALL cell survival, as its depletion by short hairpin RNA knockdown leads to apoptosis. Mechanistically, JDP2 regulates prosurvival signaling through direct transcriptional regulation of MCL1. Furthermore, JDP2 is one of few oncogenes capable of initiating T-ALL in transgenic zebrafish. Notably, thymocytes from rag2:jdp2 transgenic zebrafish express high levels of mcl1 and demonstrate resistance to steroids in vivo. These studies establish JDP2 as a novel oncogene in high-risk T-ALL and implicate overexpression of MCL1 as a mechanism of steroid resistance in JDP2-overexpressing cells.


Assuntos
Oncogenes , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Proteínas Repressoras/genética , Proteínas de Peixe-Zebra/genética , Animais , Apoptose/efeitos dos fármacos , Sequência de Bases , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Pré-Escolar , Dexametasona/farmacologia , Modelos Animais de Doenças , Elementos Facilitadores Genéticos/genética , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/farmacologia , Humanos , Lactente , Camundongos , Mutagênese Insercional/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Transplante de Neoplasias , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Ligação Proteica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Repressoras/metabolismo , Elementos de Resposta/genética , Timócitos/efeitos dos fármacos , Timócitos/metabolismo , Resultado do Tratamento , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
15.
16.
Front Immunol ; 9: 362, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29545797

RESUMO

Death receptor 3 (DR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, has been implicated in regulating T-helper type-1 (TH1), type-2 (TH2), and type-17 (TH17) responses as well as regulatory T cell (Treg) and innate lymphoid cell (ILC) functions during immune-mediated diseases. However, the role of DR3 in controlling lymphocyte functions in inflammatory bowel disease (IBD) is not fully understood. Recent studies have shown that activation of DR3 signaling modulates Treg expansion suggesting that stimulation of DR3 represents a potential therapeutic target in human inflammatory diseases, including Crohn's disease (CD). In this study, we tested a specific DR3 agonistic antibody (4C12) in SAMP1/YitFc (SAMP) mice with CD-like ileitis. Interestingly, treatment with 4C12 prior to disease manifestation markedly worsened the severity of ileitis in SAMP mice despite an increase in FoxP3+ lymphocytes in mesenteric lymph node (MLN) and small-intestinal lamina propria (LP) cells. Disease exacerbation was dominated by overproduction of both TH1 and TH2 cytokines and associated with expansion of dysfunctional CD25-FoxP3+ and ILC group 1 (ILC1) cells. These effects were accompanied by a reduction in CD25+FoxP3+ and ILC group 3 (ILC3) cells. By comparison, genetic deletion of DR3 effectively reversed the inflammatory phenotype in SAMP mice by promoting the expansion of CD25+FoxP3+ over CD25-FoxP3+ cells and the production of IL-10 protein. Collectively, our data demonstrate that DR3 signaling modulates a multicellular network, encompassing Tregs, T effectors, and ILCs, governing disease development and progression in SAMP mice with CD-like ileitis. Manipulating DR3 signaling toward the restoration of the balance between protective and inflammatory lymphocytes may represent a novel and targeted therapeutic modality for patients with CD.


Assuntos
Doença de Crohn/imunologia , Ileíte/imunologia , Membro 25 de Receptores de Fatores de Necrose Tumoral/agonistas , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Animais , Anticorpos Monoclonais/metabolismo , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Ileíte/genética , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos AKR , Camundongos Knockout , Camundongos Transgênicos , Proteínas Nucleares/genética , Membro 25 de Receptores de Fatores de Necrose Tumoral/genética , Membro 25 de Receptores de Fatores de Necrose Tumoral/imunologia , Transdução de Sinais
17.
J Nanosci Nanotechnol ; 18(2): 815-822, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29448498

RESUMO

In this study, three commercially available nanodiamonds (NDs) of similar size (about 5 nm in diameter) but with different surface chemistry (-COOH, -NH2 and -poly(ethylene glycol)) were used to study the toxicity and immune activation of Raw264.7 cells. Only ND-PEG is well dispersed in water and cell culture medium (about 10 nm in diameter), while ND-COOH and ND-NH2 only showed some aggregation, about 50 nm in water and about 100 nm in cell culture medium. The three NDs showed different zeta potentials in water but the difference disappeared in cell culture medium due to the surface adsorption of the proteins. The ND-PEG did not show any obvious signs of cytotoxicity or activation on Raw264.7 cells under tested conditions. The ND-COOH and ND-NH2 caused dose-dependent toxicity, with the amino group capped NDs being much more toxic compare to those of the carboxylic acid group at the same exposure conditions. ND-COOH induced a certain immune response in Raw264.7 cells, leading to a higher expression of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), especially with a significantly longer incubation time. ND-NH2 also induced significant expression of TNF-α and IL-6 in Raw264.7 cells at first, but this expression was reduced with a longer incubation time due to cell death.


Assuntos
Adjuvantes Imunológicos , Citocinas/metabolismo , Nanodiamantes , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/toxicidade , Adsorção , Animais , Interleucina-6 , Camundongos , Nanodiamantes/toxicidade , Células RAW 264.7 , Fator de Necrose Tumoral alfa
18.
Cancer Discov ; 8(3): 320-335, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29284669

RESUMO

The amplified MYCN gene serves as an oncogenic driver in approximately 20% of high-risk pediatric neuroblastomas. Here, we show that the family member MYC is a potent transforming gene in a separate subset of high-risk neuroblastoma cases (∼10%), based on (i) its upregulation by focal enhancer amplification or genomic rearrangements leading to enhancer hijacking, and (ii) its ability to transform neuroblastoma precursor cells in a transgenic animal model. The aberrant regulatory elements associated with oncogenic MYC activation include focally amplified distal enhancers and translocation of highly active enhancers from other genes to within topologically associating domains containing the MYC gene locus. The clinical outcome for patients with high levels of MYC expression is virtually identical to that of patients with amplification of the MYCN gene, a known high-risk feature of this disease. Together, these findings establish MYC as a bona fide oncogene in a clinically significant group of high-risk childhood neuroblastomas.Significance: Amplification of the MYCN oncogene is a recognized hallmark of high-risk pediatric neuroblastoma. Here, we demonstrate that MYC is also activated as a potent oncogene in a distinct subset of neuroblastoma cases through either focal amplification of distal enhancers or enhancer hijacking mediated by chromosomal translocation. Cancer Discov; 8(3); 320-35. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 253.


Assuntos
Elementos Facilitadores Genéticos , Neuroblastoma/genética , Proteínas Proto-Oncogênicas c-myc/genética , Animais , Animais Geneticamente Modificados , Linhagem Celular Tumoral , Criança , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Luminescentes/genética , Proteína Proto-Oncogênica N-Myc/genética , Neoplasias Experimentais/genética , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Análise de Sobrevida , Translocação Genética , Peixe-Zebra/genética
19.
Small ; 13(42)2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28902985

RESUMO

Cellulose is the most abundant natural polymer on earth, providing a sustainable green resource that is renewable, degradable, biocompatible, and cost effective. Recently, nanocellulose-based mesoporous structures, flexible thin films, fibers, and networks are increasingly developed and used in photovoltaic devices, energy storage systems, mechanical energy harvesters, and catalysts components, showing tremendous materials science value and application potential in many energy-related fields. In this Review, the most recent advancements of processing, integration, and application of cellulose nanomaterials in the areas of solar energy harvesting, energy storage, and mechanical energy harvesting are reviewed. For solar energy harvesting, promising applications of cellulose-based nanostructures for both solar cells and photoelectrochemical electrodes development are reviewed, and their morphology-related merits are discussed. For energy storage, the discussion is primarily focused on the applications of cellulose-based nanomaterials in lithium-ion batteries, including electrodes (e.g., active materials, binders, and structural support), electrolytes, and separators. Applications of cellulose nanomaterials in supercapacitors are also reviewed briefly. For mechanical energy harvesting, the most recent technology evolution in cellulose-based triboelectric nanogenerators is reviewed, from fundamental property tuning to practical implementations. At last, the future research potential and opportunities of cellulose nanomaterials as a new energy material are discussed.


Assuntos
Celulose/química , Nanoestruturas/química , Eletrodos , Energia Solar , Propriedades de Superfície , Termodinâmica
20.
Sci Rep ; 7(1): 4936, 2017 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-28694482

RESUMO

The rapid development of wearable and disposable electronic devices and the rising awareness of environmental sustainability impose growing new demands on the nature degradability of current electronic and energy systems. Here we report a new type of flexible transparent conductive paper completely made from green and earth abundant materials which are also fully degradable and recyclable. Aluminum-doped zinc oxide (AZO) was deposited by low-temperature atomic layer deposition (ALD) as the transparent conductive oxide (TCO) layer on transparent cellulose nanofibril (CNF) papers. The mesoporous structure of the CNF paper rendered strong adhesion of the AZO layer and exhibited excellent mechanical integrity and electrical conductivity within a wide range of tensile and compressive strains. The AZO-CNF paper could be completely dissolved in warm city water after one-hour stirring, demonstrating an excellent nature degradability. A flexible and transparent triboelectric nanogenerator (TENG) was further fabricated using such AZO-CNF papers with a performance that was comparable to other synthetic polymer-based systems. This work illustrated a new and promising strategy of utilizing 100% green and degradable materials in novel electronic and energy harvesting devices.


Assuntos
Planeta Terra , Condutividade Elétrica , Eletricidade , Alumínio/química , Nanofibras/química , Óxido de Zinco/química
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