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1.
Nanoscale ; 14(21): 7913-7918, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35593223

RESUMO

Interfacial heating is the most obvious feature that distinguishes the novel solar driven interfacial heating from the traditional solar heating technology, and it is also a key factor in promoting solar energy utilization and vapor generation performance. However, the inherent trade-off between water supply and the interfacial heating performance of photothermal materials has rarely been investigated. Herein, an all-in-one designed bilayer evaporator consisting of a top solar absorber (Fe3O4@PDA-SA) and a bottom water transport layer (SA) is reported. This bilayer structured aerogel can provide good thermal insulation, effective water transmission channels, and reliable light absorbance, and perform well as a high-quality solar steam evaporator with the evaporation rate of approximately 1.517 kg m-2 h-1 and the evaporation efficiency of approximately 98.27% under 1 kW m-2 solar illumination. Most importantly, we can control the pore size of the bottom layer by a simple free water evaporation method, so as to manipulate the water transport capacity of materials. There is flexibility to change the water content of the light-absorbing structure and further explore the influence of water supply on the interfacial heating performance of the evaporator, which provides more possibilities for the design and preparation of high-quality solar steam evaporators.

2.
Nat Cell Biol ; 21(5): 579-591, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30962574

RESUMO

It is well established that ferroptosis is primarily controlled by glutathione peroxidase 4 (GPX4). Surprisingly, we observed that p53 activation modulates ferroptotic responses without apparent effects on GPX4 function. Instead, ALOX12 inactivation diminishes p53-mediated ferroptosis induced by reactive oxygen species stress and abrogates p53-dependent inhibition of tumour growth in xenograft models, suggesting that ALOX12 is critical for p53-mediated ferroptosis. The ALOX12 gene resides on human chromosome 17p13.1, a hotspot of monoallelic deletion in human cancers. Loss of one Alox12 allele is sufficient to accelerate tumorigenesis in Eµ-Myc lymphoma models. Moreover, ALOX12 missense mutations from human cancers abrogate its ability to oxygenate polyunsaturated fatty acids and to induce p53-mediated ferroptosis. Notably, ALOX12 is dispensable for ferroptosis induced by erastin or GPX4 inhibitors; conversely, ACSL4 is required for ferroptosis upon GPX4 inhibition but dispensable for p53-mediated ferroptosis. Thus, our study identifies an ALOX12-mediated, ACSL4-independent ferroptosis pathway that is critical for p53-dependent tumour suppression.


Assuntos
Araquidonato 12-Lipoxigenase/genética , Carcinogênese/genética , Glutationa Peroxidase/genética , Proteína Supressora de Tumor p53/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Glutationa Peroxidase/antagonistas & inibidores , Humanos , Peroxidação de Lipídeos/genética , Linfoma/genética , Linfoma/patologia , Camundongos , Mutação de Sentido Incorreto/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Espécies Reativas de Oxigênio , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Diagn Interv Radiol ; 24(6): 372-377, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30373725

RESUMO

PURPOSE: We aimed to evaluate the role of cone-beam computed tomography (CT) performed as an adjunct to angiography for the determination of feeding vessels responsible for bleeding during arterial embolization for massive hemoptysis. METHODS: In this retrospective study, 23 patients with massive hemoptysis who underwent cone-beam CT evaluation prior to arterial embolization from December 2014 to December 2017 were included. During the angiographic session, two interventional radiologists selected the possible feeding vessels that were likely to supply the bleeding target lesions. Contrast-enhanced cone-beam CT was performed at the indefinite feeding arteries as an adjunct to angiography to determine whether the artery was a real feeding vessel, based on whether the target lesion was detected in the perfused territory of the study artery on images. RESULTS: Selective cone-beam CT was successfully performed in 21 patients, at 26 possible feeding vessels that were detected by selective angiography. Cone-beam CT determined the feeding vessel in 24 arteries (92.3%) in 19 patients (90.5%). As a result of cone-beam CT findings, 16 of 24 study arteries were judged as definitively not feeding vessels (66.7%) and the remaining 8 study arteries were judged as definitively feeding vessels (33.3%). In 2 of 26 study arteries cone-beam CT could not determine the feeding vessel (7.7%). CONCLUSION: Cone-beam CT performed as an adjunctive technique to angiography is sufficient to provide adequate information for confident determination of the feeding vessel, which is essential for the operators to perform accurate embolization during arterial embolization for massive hemoptysis.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Embolização Terapêutica/métodos , Hemoptise/diagnóstico por imagem , Hemoptise/terapia , Radiografia Intervencionista/métodos , Sistema Respiratório/irrigação sanguínea , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Respiratório/diagnóstico por imagem , Estudos Retrospectivos
4.
Oncotarget ; 9(7): 7282-7297, 2018 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-29484110

RESUMO

Although cell-cycle arrest, senescence and apoptosis remain as major canonical activities of p53 in tumor suppression, the emerging role of p53 in metabolism has been a topic of great interest. Nevertheless, it is not completely understood how p53-mediated metabolic activities are regulated in vivo and whether this part of the activities has an independent role beyond tumor suppression. Mdmx (also called Mdm4), like Mdm2, acts as a major suppressor of p53 but the embryonic lethality of mdmx-null mice creates difficulties to evaluate its physiological significance in metabolism. Here, we report that the embryonic lethality caused by the deficiency of mdmx, in contrast to the case for mdm2, is fully rescued in the background of p533KR/3KR , an acetylation-defective mutant unable to induce cell-cycle arrest, senescence and apoptosis. p533KR/3KR/mdmx-/- mice are healthy but skinny without obvious developmental defects. p533KR/3KR/mdmx-/- mice are resistant to fat accumulation in adipose tissues upon high fat diet. Notably, the levels of p53 protein are only slightly increased and can be further induced upon DNA damage in p533KR/3KR/mdmx-/- mice, suggesting that Mdmx is only partially required for p53 degradation in vivo. Further analyses indicate that the anti-obesity phenotypes in p533KR/3KR/mdmx-/- mice are caused by activation of lipid oxidation and thermogenic programs in adipose tissues. These results demonstrate the specific effects of the p53/Mdmx axis in lipid metabolism and adipose tissue remodeling and reveal a surprising role of Mdmx inhibition in anti-obesity effects beyond, commonly expected, tumor suppression. Thus, our study has significant implications regarding Mdmx inhibitors in the treatment of obesity related diseases.

5.
Oncotarget ; 7(11): 11838-49, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26943586

RESUMO

Although p53-mediated cell cycle arrest, senescence and apoptosis are well accepted as major tumor suppression mechanisms, the loss of these functions does not directly lead to tumorigenesis, suggesting that the precise roles of these canonical activities of p53 need to be redefined. Here, we report that the cells derived from the mutant mice expressing p533KR, an acetylation-defective mutant that fails to induce cell-cycle arrest, senescence and apoptosis, exhibit high levels of aneuploidy upon DNA damage. Moreover, the embryonic lethality caused by the deficiency of XRCC4, a key DNA double strand break repair factor, can be fully rescued in the p533KR/3KR background. Notably, despite high levels of genomic instability, p533KR/3KRXRCC4-/- mice, unlike p53-/- XRCC4-/- mice, are not succumbed to pro-B-cell lymphomas. Nevertheless, p533KR/3KR XRCC4-/- mice display aging-like phenotypes including testicular atrophy, kyphosis, and premature death. Further analyses demonstrate that SLC7A11 is downregulated and that p53-mediated ferroptosis is significantly induced in spleens and testis of p533KR/3KRXRCC4-/- mice. These results demonstrate that the direct role of p53-mediated cell cycle arrest, senescence and apoptosis is to control genomic stability in vivo. Our study not only validates the importance of ferroptosis in p53-mediated tumor suppression in vivo but also reveals that the combination of genomic instability and activation of ferroptosis may promote aging-associated phenotypes.


Assuntos
Senilidade Prematura/fisiopatologia , Pontos de Checagem do Ciclo Celular , Instabilidade Genômica , Linfoma de Células B/patologia , Proteína Supressora de Tumor p53/fisiologia , Animais , Apoptose , Proliferação de Células , Transformação Celular Neoplásica , Dano ao DNA , Reparo do DNA , Proteínas de Ligação a DNA/fisiologia , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Camundongos , Camundongos Knockout , Células Tumorais Cultivadas
6.
Nature ; 520(7545): 57-62, 2015 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-25799988

RESUMO

Although p53-mediated cell-cycle arrest, senescence and apoptosis serve as critical barriers to cancer development, emerging evidence suggests that the metabolic activities of p53 are also important. Here we show that p53 inhibits cystine uptake and sensitizes cells to ferroptosis, a non-apoptotic form of cell death, by repressing expression of SLC7A11, a key component of the cystine/glutamate antiporter. Notably, p53(3KR), an acetylation-defective mutant that fails to induce cell-cycle arrest, senescence and apoptosis, fully retains the ability to regulate SLC7A11 expression and induce ferroptosis upon reactive oxygen species (ROS)-induced stress. Analysis of mutant mice shows that these non-canonical p53 activities contribute to embryonic development and the lethality associated with loss of Mdm2. Moreover, SLC7A11 is highly expressed in human tumours, and its overexpression inhibits ROS-induced ferroptosis and abrogates p53(3KR)-mediated tumour growth suppression in xenograft models. Our findings uncover a new mode of tumour suppression based on p53 regulation of cystine metabolism, ROS responses and ferroptosis.


Assuntos
Cistina/metabolismo , Ferro/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Sistema y+ de Transporte de Aminoácidos/biossíntese , Sistema y+ de Transporte de Aminoácidos/deficiência , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Animais , Transporte Biológico , Morte Celular , Embrião de Mamíferos/embriologia , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário , Humanos , Camundongos , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-mdm2/deficiência , Proteínas Proto-Oncogênicas c-mdm2/genética , Especificidade por Substrato , Proteína Supressora de Tumor p53/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Cell Cycle ; 12(5): 753-61, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23343762

RESUMO

It is well established that the p53 tumor suppressor plays a crucial role in controlling cell proliferation and apoptosis upon various types of stress. There is increasing evidence showing that p53 is also critically involved in various metabolic pathways, both in tumor and normal cells. Here, we have identified a novel p53 metabolic target pantothenate kinase-1 (PANK1) via ChIP-on-chip. PanK1 catalyzes the rate-limiting step for CoA synthesis and, therefore, controls intracellular CoA content; Pank1-knockout mice exhibit defect in ß-oxidation and gluconeogenesis in the liver after starvation due to insufficient CoA levels. We demonstrated that PANK1 gene is a direct transcriptional target of p53. Although DNA damage-induced p53 upregulates PanK1 expression, depletion of PanK1 expression does not affect p53-dependent growth arrest or apoptosis. Interestingly, upon glucose starvation, PanK1 expression is significantly reduced in HCT116 p53 (-/-) but not in HCT116 p53 (+/+) cells, suggesting that p53 is required to maintain PanK1 expression under metabolic stress conditions. Moreover, by using p53-mutant mice, we observed that, similar to the case in Pank1-knockout mice, gluconeogenesis is partially impaired in p53-null mice. Together, our findings show that p53 plays an important role in regulating energy homeostasis through transcriptional control of PANK1, independent of its canonical functions in apoptosis and cell cycle arrest.


Assuntos
Fosfotransferases (Aceptor do Grupo Álcool)/genética , Ativação Transcricional/genética , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/genética , Sequência de Bases , Dano ao DNA/genética , Regulação Neoplásica da Expressão Gênica , Gluconeogênese/genética , Células HCT116 , Humanos , Camundongos , Dados de Sequência Molecular , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Proteína Supressora de Tumor p53/deficiência
8.
Cell ; 149(6): 1269-83, 2012 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-22682249

RESUMO

Cell-cycle arrest, apoptosis, and senescence are widely accepted as the major mechanisms by which p53 inhibits tumor formation. Nevertheless, it remains unclear whether they are the rate-limiting steps in tumor suppression. Here, we have generated mice bearing lysine to arginine mutations at one (p53(K117R)) or three (p53(3KR); K117R+K161R+K162R) of p53 acetylation sites. Although p53(K117R/K117R) cells are competent for p53-mediated cell-cycle arrest and senescence, but not apoptosis, all three of these processes are ablated in p53(3KR/3KR) cells. Surprisingly, unlike p53 null mice, which rapidly succumb to spontaneous thymic lymphomas, early-onset tumor formation does not occur in either p53(K117R/K117R) or p53(3KR/3KR) animals. Notably, p53(3KR) retains the ability to regulate energy metabolism and reactive oxygen species production. These findings underscore the crucial role of acetylation in differentially modulating p53 responses and suggest that unconventional activities of p53, such as metabolic regulation and antioxidant function, are critical for suppression of early-onset spontaneous tumorigenesis.


Assuntos
Apoptose , Pontos de Checagem do Ciclo Celular , Senescência Celular , Proteína Supressora de Tumor p53/metabolismo , Sequência de Aminoácidos , Animais , Fibroblastos/metabolismo , Técnicas de Introdução de Genes , Humanos , Linfoma/metabolismo , Camundongos , Dados de Sequência Molecular , Mutação , Neoplasias/genética , Neoplasias/metabolismo , Alinhamento de Sequência , Neoplasias do Timo/metabolismo , Proteína Supressora de Tumor p53/genética
9.
Cell Cycle ; 6(13): 1646-54, 2007 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-17611414

RESUMO

Human DDX11 and DDX12 are closely related genes encoding the helicases ChlR1 and ChlR2, which belong to the CHL1 DNA helicase family. Recently, it was shown that human ChlR1 interacts with components of the cohesin complex and is required for proper centromeric cohesion. To establish the function of ChlR1 in development we made a mutant mouse lacking Ddx11, the single mouse ChlR gene. The absence of Ddx11 resulted in embryonic lethality at E10.5. The mutant embryos were smaller in size, malformed and exhibited sparse cellularity in comparison to normal or heterozygous litter mates. Importantly, loss of Ddx11 resulted in the inability to form a proper placenta, indicating that ChlR1 is essential for placental formation. Detailed analysis of cells isolated from Ddx11-/- embryos revealed a G2/M cell cycle delay, an increased frequency of chromosome missegregation, decreased chromosome cohesion, and increased aneuploidy. To examine whether ChlR proteins are required for arm cohesion and for loading of the cohesin complex, further studies were preformed in ChlR1 siRNA treated cells. These studies revealed that ChlR1 is required for proper sister chromatid arm cohesion and that cohesin complexes bind more loosely to chromatin in the absence of ChlR1. Taken together, these studies provide the first data indicating that the ChlR1 helicase is essential for proper binding of the cohesin complex to both the centromere and the chromosome arms, and indicate that ChlR1 is essential for embryonic development and the prevention of aneuploidy in mammals.


Assuntos
Aneuploidia , RNA Helicases DEAD-box/genética , Desenvolvimento Embrionário/genética , Placenta/anormalidades , Prenhez , Troca de Cromátide Irmã/genética , Animais , Apoptose/genética , Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Segregação de Cromossomos/genética , Feminino , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitose/genética , Proteínas Nucleares/metabolismo , Gravidez , Prenhez/genética , Coesinas
11.
Mol Cell Biol ; 24(8): 3188-97, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15060143

RESUMO

The CDK11(p110) protein kinases are part of large-molecular-weight complexes that also contain RNA polymerase II, transcriptional elongation factors, and general pre-mRNA splicing factors. CDK11(p110) isoforms may therefore couple transcription and pre-mRNA splicing by their effect(s) on certain proteins required for these processes. The CDK11(p58) kinase isoform is generated from the CDK11(p110) mRNA through the use of an internal ribosome entry site in a mitosis-specific manner, suggesting that this kinase may regulate the cell cycle during mitosis. The in vivo role and necessity of CDK11(p110/p58) kinase function during mammalian development were examined by generating CDK11(p110/p58)-null mice through targeted disruption of the corresponding gene using homologous recombination. While heterozygous mice develop normally, disruption of both CDK11(p110/p58) alleles results in early embryonic lethality due to apoptosis of the blastocyst cells between 3.5 and 4 days postcoitus. Cells within these embryos exhibit both proliferative defect(s) and a mitotic arrest. These results are consistent with the proposed cellular functions of the CDK11(p110/p58) kinases and confirm that the CDK11(p110/p58) kinases are essential for cellular viability as well as normal early embryonic development.


Assuntos
Blastocisto/fisiologia , Quinases Ciclina-Dependentes/metabolismo , Mitose/fisiologia , Animais , Apoptose/fisiologia , Blastocisto/citologia , Caspase 3 , Caspases/metabolismo , Divisão Celular/fisiologia , Tamanho Celular , Quinases Ciclina-Dependentes/genética , Viabilidade Fetal , Marcação de Genes , Marcação In Situ das Extremidades Cortadas , Isoenzimas/genética , Isoenzimas/metabolismo , Camundongos , Camundongos Knockout
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