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1.
Hepatology ; 77(1): 124-143, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35429173

RESUMO

BACKGROUND AIMS: As a global health threat, NASH has been confirmed to be a chronic progressive liver disease that is strongly associated with obesity. However, no approved drugs or efficient therapeutic strategies are valid, mainly because its complicated pathological processes is underestimated. APPROACH RESULTS: We identified the RING-type E3 ubiquitin transferase-tripartite motif-containing protein 31 (TRIM31), a member of the E3 ubiquitin ligases family, as an efficient endogenous inhibitor of transforming growth factor-beta-activated kinase 1 (mitogen-activated protein kinase kinase kinase 7; MAP3K7), and we further confirmed that TRIM31 is an MAP3K7-interacting protein and promotes MAP3K7 degradation by enhancing ubiquitination of K48 linkage in hepatocytes. Hepatocyte-specific Trim31 deletion blocks hepatic metabolism homeostasis, concomitant with glucose metabolic syndrome, lipid accumulation, up-regulated inflammation, and dramatically facilitates NASH progression. Inversely, transgenic overexpression, lentivirus, or adeno-associated virus-mediated Trim31 gene therapy restrain NASH in three dietary mice models. Mechanistically, in response to metabolic insults, TRIM31 interacts with MAP3K7 and conjugates K48-linked ubiquitination chains to promote MAP3K7 degradation, thus blocking MAP3K7 abundance and its downstream signaling cascade activation in hepatocytes. CONCLUSIONS: TRIM31 may serve as a promising therapeutic target for NASH treatment and associated metabolic disorders.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases , Animais , Camundongos , MAP Quinase Quinase Quinases/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Humanos , Proteínas com Motivo Tripartido/metabolismo
2.
Exp Cell Res ; 430(1): 113721, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37437769

RESUMO

The hepatitis B Virus X (HBx) protein plays a crucial role in the HBV-induced hepatic steatosis. Fatty acid transport protein 2 (FATP2) is a key protein that is involved in hepatic lipogenesis, and it was found to be highly expressed in various metabolic diseases. However, Whether FATP2 is a key factor in the pathogenesis of HBx-induced hepatic steatosis remains unclear. In this study, we found that FATP2 was up-regulated by HBx in vitro and in vivo and participated in HBx-induced hepatic lipid accumulation. Treatment of HBx-expressing cell lines and mice with FATP2 inhibitor (FATP2i) lipofermata ameliorated HBx-induced lipid accumulation and reduced oxidative stress and inflammation caused by lipid accumulation. Moreover, the liver injury of mouse was restored after FATP2i treatment. In summary, our results reveal that FATP2 is a key driver factor for HBx-induced hepatic lipid accumulation, and inhibition of FATP2 can ameliorates lipid accumulation caused by HBx. This study provides new insights into the mechanism of HBV-induced hepatic steatosis.


Assuntos
Fígado Gorduroso , Camundongos , Animais , Regulação para Cima , Fígado Gorduroso/metabolismo , Linhagem Celular , Lipídeos , Vírus da Hepatite B/fisiologia
3.
Small ; 18(51): e2204924, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36336642

RESUMO

Water oxidation is one of the most challenging steps in CO2 photoreduction, but its influence on CO2 photoreduction is still poorly understood. Herein, the concept of accelerating the water oxidation kinetics to promote the CO2 photoreduction is realized by incorporating supramolecular porphyrin nanosheets (NS) into the C3 N4 catalyst. As a prototype, porphyrin-C3 N4 based van der Waals heterojunctions with efficient charge separation are elaborately designed, in which the porphyrin and C3 N4 NS serve as the water oxidation booster and CO2 reduction center, respectively. Theoretical calculations and relevant experiments demonstrate that the added porphyrin NS reverses the rate-limiting step in the water oxidation while reducing its energy barrier, thus resulting in faster reaction kinetics. Therefore, the optimal sample shows excellent performance in visible-light-driven CO2 reduction with a maximum CO evolution rate of 16.8 µmol g-1 h-1 , which is 6.8 times that of the C3 N4 NS and reaches the current state of the art for C3 N4 -based materials in CO2 photoreduction. Overall, this work throws light that accelerating water oxidation kinetics can effectively improve the CO2 photoreduction efficiency.

4.
Hepatology ; 73(4): 1346-1364, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32592194

RESUMO

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) has been widely recognized as a precursor to metabolic complications. Elevated inflammation levels are predictive of NAFLD-associated metabolic disorder. Inactive rhomboid-like protein 2 (iRhom2) is regarded as a key regulator in inflammation. However, the precise mechanisms by which iRhom2-regulated inflammation promotes NAFLD progression remain to be elucidated. APPROACH AND RESULTS: Here, we report that insulin resistance, hepatic steatosis, and specific macrophage inflammatory activation are significantly alleviated in iRhom2-deficient (knockout [KO]) mice, but aggravated in iRhom2 overexpressing mice. We further show that, mechanistically, in response to a high-fat diet (HFD), iRhom2 KO mice and mice with iRhom2 deficiency in myeloid cells only showed less severe hepatic steatosis and insulin resistance than controls. Inversely, transplantation of bone marrow cells from healthy mice to iRhom2 KO mice expedited the severity of insulin resistance and hepatic dyslipidemia. Of note, in response to HFD, hepatic iRhom2 binds to mitogen-activated protein kinase kinase kinase 7 (MAP3K7) to facilitate MAP3K7 phosphorylation and nuclear factor kappa B cascade activation, thereby promoting the activation of c-Jun N-terminal kinase/insulin receptor substrate 1 signaling, but disturbing AKT/glycogen synthase kinase 3ß-associated insulin signaling. The iRhom2/MAP3K7 axis is essential for iRhom2-regulated liver steatosis. CONCLUSIONS: iRhom2 may represent a therapeutic target for the treatment of HFD-induced hepatic steatosis and insulin resistance.


Assuntos
Proteínas de Transporte/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fígado/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ativação Metabólica , Animais , Proteínas de Transporte/biossíntese , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Progressão da Doença , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/fisiopatologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Resistência à Insulina/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Fígado/fisiopatologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Transdução de Sinais
5.
Chemistry ; 28(16): e202104514, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35118722

RESUMO

Exploring new catalytic strategies for achieving efficient CO2 hydrogenation under mild conditions is of great significance for environmental remediation. Herein, a composite photocatalyst Zr-based MOF encapsulated plasmonic AuPt alloy nanoparticles (AuPt@UiO-66-NH2 ) was successfully constructed for the efficient photothermal catalysis of CO2 hydrogenation. Under light irradiation at 150 °C, AuPt@UiO-66-NH2 achieved a CO production rate of 1451 µmol gmetal -1 h-1 with 91 % selectivity, which far exceeded those obtained by Au@Pt@UiO-66-NH2 with Pt shell on Au (599 µmol gmetal -1 h-1 ) and Au@UiO-66-NH2 (218 µmol gmetal -1 h-1 ). The outstanding performances of AuPt@UiO-66-NH2 were attributed to the synergetic effect originating from the plasmonic metal Au, doped active metal Pt, and encapsulation structure of UiO-66-NH2 shell. This work provides a new way for photothermal catalysis of CO2 and a reference for the design of high-performance plasmonic catalysts.

6.
Chemistry ; 28(4): e202103521, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-34788502

RESUMO

Ethanol is a promising liquid clean energy source in the energy conversion field. However, the self-poisoning caused by the strongly adsorbed reaction intermediates (typically, CO) is a critical problem in ethanol oxidation reaction. To address this issue, we proposed a joint use of two strategies, alloying of Pt with other metals and building Pt/metal-oxide interfaces, to achieve high-performance electrocatalytic ethanol oxidation. For this, a well-designed synthetic route combining wet impregnation with a two-step thermal treatment process was established to construct PtSn/SnOx interfaces on carbon nanotubes. Using this route, the alloying of Pt-Sn and formation of PtSn-SnOx interfaces can simultaneously be achieved, and the coverage of SnOx thin films on PtSn alloy nanoparticles can be facilely tuned by the strong interaction between Pt and SnOx . The results revealed that the partial coverage of SnOx species not only retained the active sites, but also enhanced the CO anti-poisoning ability of the catalyst. Consequently, the H-PtSn/SnOx /CNT-2 catalyst with an optimized PtSn-SnOx interface showed significantly improved performances toward the ethanol oxidation reaction (825 mA mgPt -1 ). This study provides deep insights into the structure-performance relationship of PtSn/metal oxide composite catalysts, which would be helpful for the future design and fabrication of high-performance Pt-based ethanol oxidation reaction catalysts.

7.
Int J Mol Sci ; 23(14)2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35887045

RESUMO

Chronic alcohol exposure can lead to liver pathology relating to inflammation and oxidative stress, which are two of the major factors in the incidence of liver fibrosis and even liver cancer. The underlying molecular mechanisms regarding hepatic lesions associated with alcohol are not fully understood. Considering that the recently identified iRhom2 is a key pathogenic mediator of inflammation, we performed in vitro and in vivo experiments to explore its regulatory role in alcohol-induced liver fibrosis. We found that iRhom2 knockout significantly inhibited alcohol-induced inflammatory responses in vitro, including elevated expressions of inflammatory cytokines (IL-1ß, IL-6, IL-18, and TNF-α) and genes associated with inflammatory signaling pathways, such as TACE (tumor necrosis factor-alpha converting enzyme), TNFR1 (tumor necrosis factor receptor 1), and TNFR2, as well as the activation of NF-κB. The in vivo results confirmed that long-term alcohol exposure leads to hepatocyte damage and fibrous accumulation. In this pathological process, the expression of iRhom2 is promoted to activate the TACE/NF-κB signaling pathway, leading to inflammatory responses. Furthermore, the deletion of iRhom2 blocks the TACE/NF-κB signaling pathway and reduces liver damage and fibrosis caused by alcohol. Additionally, the activation of the JNK/Nrf2/HO-1 signaling pathway caused by alcohol exposure was also noted in vitro and in vivo. In the same way, knockout or deleting iRhom2 blocked the JNK/Nrf2/HO-1 signaling pathway to regulate the oxidative stress. Therefore, we contend that iRhom2 is a key regulator that promotes inflammatory responses and regulates oxidative stress in alcoholic liver fibrosis lesions. We posit that iRhom2 is potentially a new therapeutic target for alcoholic liver fibrosis.


Assuntos
Proteínas de Transporte , Inflamação , Peptídeos e Proteínas de Sinalização Intracelular , Cirrose Hepática Alcoólica , Estresse Oxidativo , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática Alcoólica/genética , Cirrose Hepática Alcoólica/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Transdução de Sinais
8.
Genomics ; 112(1): 683-693, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31075388

RESUMO

BACKGROUND: Recent studies discovered many genetic variants associated with both psychiatric and inflammatory disorders, but the role of genetic factors in the development of psychiatric comorbidity (PC) in inflammatory bowel disease (IBD) is underexplored. Particularly, it has been shown that some of the genetic variants have been linked to the concentrations of circulating cytokines and symptoms of the inflammatory cytokine-associated depression. We analysed genomic features of individuals with IBD by comparing IBD patients with PC with those who have IBD but without PC. We hypothesized that cytokine related signalling pathways may be significantly associated with the psychiatric comorbidity in patients with IBD. METHODS: Individuals enrolled in the Manitoba IBD Cohort Study were separated to two groups accordingly to the presence of PC. A sample set comprising 97 IBD individuals with PC (IBD + PC) and 146 IBD individuals without PC (IBD) was first used to identify copy number variations (CNVs) from genome-wide genetic data using three different detection algorithms. IBD + PC and IBD groups were compared by the number of CNVs overlapping each gene; deletions and duplications were analysed separately. Gene set overrepresentation analysis was then conducted using CNV-overlapped genes and the candidate gene sets of neurological and immunological relevance. RESULTS: Medium-sized CNV (size between 100 and 500 kilobase pairs)-burden is significantly higher in IBD + PC than IBD groups. Gene-based CNV association analysis did not show significant differences between the two IBD groups. Gene set overrepresentation analysis demonstrated the significant enrichment of gene sets related to cytokine signalling pathways by the genes overlapped by deletions in the IBD individuals with PC. CONCLUSION: Our results confirm the role of cytokine signalling pathways in the development of PC in IBD. Additionally, our results warrant further study with a larger sample size focusing on cytokine SNPs to further understand the relationship between inflammatory and psychiatric disorders.


Assuntos
Citocinas/genética , Variações do Número de Cópias de DNA , Transtornos Mentais/genética , Polimorfismo de Nucleotídeo Único , Transdução de Sinais/genética , Adolescente , Adulto , Comorbidade , Feminino , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos
9.
Nano Lett ; 20(7): 5458-5464, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32492344

RESUMO

Atomic edge sites on two-dimensional (2D) nanomaterials display striking catalytic behavior, whereas edge engineering for 2D metal nanocatalysts remains an insurmountable challenge. Here we advance a one-pot synthesis of ultrathin 2D PdPtCu trimetallic nanosheets and nanorings with escalating low-coordinated edge proportions from 11.74% and 23.11% to 45.85% as cutting-edge ethanol oxidation reaction (EOR) electrocatalysts. This in situ edge enrichment hinges on a competitive surface capping and etching strategy with integrated manipulation of the reaction kinetics. Electrocatalysis tests demystify an edge-relied EOR performance, where the edge-richest 9.0 nm-Pd61Pt22Cu17 nanorings attain an exceptional activity (12.42 A mg-1Pt+Pd, 20.2 times that of commercial Pt/C) with substantially improved durability. Molecularly mechanistic studies certify that the unsaturated edge sites on these 2D catalysts prevail, triggering the C-C bond scission and succeeding CO removal to facilitate a 12-electron-transferring EOR process. This study introduces the "metal-edge-driven" concept and enables the "edge sites on 2D multimetallic nanocatalysts" technique to design versatile heterocatalysts.

10.
Acc Chem Res ; 51(11): 2880-2887, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30346701

RESUMO

Tailoring the surface structures of nanocrystals is an exciting research area on account of appealing surface-dependent properties in various applications. Although significant progress has been made in recent years, current synthetic approaches are mainly dependent upon trial and error because of the ambiguous roles of various influencing factors in complicated environments. Therefore, a general theory for predicting and guiding the rationally controlled synthesis of micro- and nanocrystallites with specific surface structures is highly desired. Of note, previous research attention was mainly focused on the crystal growth in near equilibrium conditions. However, in supersaturated growth environments (nonequilibrium conditions), the corresponding crystal growth theories are still limited. Recently, the supersaturation-controlled surface structure strategy, which is derived from thermodynamics and the Thomson-Gibbs equation, has opened up a new avenue for the control the surface structures of crystals. This strategy involves manipulating the supersaturation of growth units to control the surface structure of micro- and nanocrystallites, as the surface energy of exposed facets is correlated to the supersaturation of growth blocks. Based on the proposed theory, micro- and nanocrystallites with various surface structures, especially high-energy facets, have been successfully synthesized by our group and other researchers in past years. In order to draw lessons from previous studies, it is imperative to give a timely research account related to the supersaturation strategy and corresponding applications in controlling surface structures of different crystallites. In this Account, we explore the supersaturation-controlled surface structure strategy to construct functional nanomaterials with desired architectures. First, we highlight the role of supersaturation of growth units from theoretical analysis after a short introduction of fundamental principles for crystal growth. Then, some detailed cases concerning evolution of surface structures are presented to highlight the key experimental factors involved in manipulating the supersaturation of growth units during synthetic processes. These factors include solvents, reaction rates, and additives in wet chemical routes as well as overpotential in electrochemical routes. In addition, we briefly discuss the role of supersaturation in growth kinetics with focus on explaining the formation of spherical micro- and nanocrystallites at extremely high supersaturation. Finally, a general summary of the supersaturation-dependent surface structure control and future prospects in this field are provided. It is expected that this Account will deepen the current understanding on fundamental principles behind the control of surface structures of micro- and nanocrystallites, which can help us to construct desirable nanomaterials and promote their practical applications.

11.
J Am Chem Soc ; 140(36): 11232-11240, 2018 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-30117323

RESUMO

Developing active and durable electro-catalysts toward ethanol oxidation reaction (EOR) with high selectivity toward the C-C bond cleavage is an important issue for the commercialization of direct ethanol fuel cell. Unfortunately, current ethanol oxidation electro-catalysts (e.g., Pt, Pd) still suffer from poor selectivity for direct oxidation of ethanol to CO2, and rapid activity degradation. Here we report a facile route to the synthesis of a new kind of cyclic penta-twinned (CPT) Rh nanostructures that are self-supported nanobranches (NBs) built with 1-dimension CPT nanorods as subunits. Structurally, the as-prepared Rh NBs possess high percentage of open {100} facets with significant CPT-induced lattice strains. With these unique structural characteristics, the as-prepared CPT Rh NBs exhibit outstanding electrocatalytic performance toward EOR in alkaline solution. Most strikingly, the selectivity of complete conversion ethanol to CO2 on the CPT Rh NBs is measured to be as high as 14.5 ± 1.1% at -0.15 V, far exceeding that for single-crystal tetrahedral nanocrystals, icosahedral nanocrystals, and commercial Rh black, as well as majority of reported values for Pt or Pd-based electro-catalysts. By combining with density functional theory calculation, the effects of different structural features of Rh on EOR are definitively elucidated. It was found that the large amount of open Rh (100) facets dominantly contribute to the outstanding activity and exceptionally high selectivity, while the additional tensile strain on (100) planes can further boost the catalytic activity by enhancing the adsorption strength and lowering the reaction barrier of dehydrogenation process of ethanol. As a proof of concept, the present work shows that rationally optimizing surface and electronic structure of electro-catalysts by simultaneously engineering their surface and bulk structures is a promising strategy to promote the performance of electro-catalysts.

12.
Small ; 13(33)2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28675780

RESUMO

Functional nanoparticles encapsulated within metal-organic frameworks (MOFs) as an emerging class of composite materials attract increasing attention owing to their enhanced or even novel properties caused by the synergistic effect between the two functional materials. However, there is still no ideal composite structure as platform to systematically analyze and evaluate the relation between the enhanced catalytic performance of composites and the structure of MOF shells. In this work, taking RhCoNi ternary alloy nanoflowers, for example, first the RhCoNi@MOF composite catalysts sheathed with different structured MOFs via a facile self-sacrificing template process are successfully fabricated. The structure type of MOF shells is easily adjustable by using different organic molecules as etchant and coordination reagent (e.g., 2,5-dihydroxyterephthalic acid or 2-methylimidazole), which can dissolve out the Co or Ni element in the alloy template in a targeted manner, thereby producing ZIF-67(Co) or MOF-74(Ni) shells accordingly. With the difference between the two MOF shells in the aperture sizes, the as-prepared two RhCoNi@MOF composites preform distinct size selectivity during the alkene hydrogenation. This work would help us to get more comprehensive understanding of the intrinsic role of MOFs behind the enhanced catalytic performance of nanoparticle@MOF composites.

13.
Chemistry ; 23(47): 11397-11403, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28600870

RESUMO

Noble metal nanoparticles embedded in metal-organic frameworks (MOFs) are composite catalysts with enhanced or novel properties compared to the pristine counterparts. In recent years, to determine the role of MOFs during catalytic process, most studies have focussed on the confinement effect of MOFs, but ignored the structural flexibility of MOFs. In this study, we use two composite catalysts, Pt@ZIF-8 [Zn(mIM)2 , mIM=2-methyl imidazole] with flexible structure and Pt@ZIF-71 [Zn(DClIM)2 , DClIM=4,5-dichloroimidazole] with rigid structure, and hydrogenation of cinnamaldehyde as model reaction, to show the confinement effect and the structure flexibility of MOF matrices on the catalytic performance of composite catalysts. Both catalysts showed high selectivity for cinnamic alcohol with the confinement effect of the aperture. But, compared to Pt@ZIF-71, Pt@ZIF-8 exhibited higher conversion but lower selectivity owing to the flexible structure. The above results remind us that we will have to consider both the aperture size of MOFs and structure flexibility to select the proper MOF matrices for the composite materials to achieve the optimized performance.

14.
Angew Chem Int Ed Engl ; 55(31): 9021-5, 2016 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-27325395

RESUMO

Excavated polyhedral noble-metal materials that were built by the orderly assembly of ultrathin nanosheets have both large surface areas and well-defined facets, and therefore could be promising candidates for diverse important applications. In this work, excavated cubic Pt-Sn alloy nanocrystals (NCs) with {110} facets were constructed from twelve nanosheets by a simple co-reduction method with the assistance of the surface regulator polyvinylpyrrolidone. The specific surface area of the excavated cubic Pt-Sn NCs is comparable to that of commercial Pt black despite their larger particle size. The excavated cubic Pt-Sn NCs exhibited superior electrocatalytic activity in terms of both the specific area current density and the mass current density towards methanol oxidation.

15.
Carcinogenesis ; 36(9): 956-62, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26014353

RESUMO

Polymorphisms in the vascular endothelial growth factor (VEGF)/angiogenesis pathway have been implicated previously in cancer risk, prognosis and response to therapy including in esophageal adenocarcinoma. Prior esophageal adenocarcinoma studies focused on using candidate polymorphisms, limiting the discovery of novel polymorphisms. Here, we applied the tagSNP (single nucleotide polymorphism) approach to identify new VEGF pathway polymorphisms associated with esophageal adenocarcinoma prognosis and validated them in an independent cohort of esophageal adenocarcinoma patients. In 231 esophageal adenocarcinoma patients of all stages/treatment plans, 58 genetic polymorphisms (18 KDR, 7 VEGFA and 33 FLT1) selected through tagging and assessment of predicted function were genotyped. Cox-proportional hazard models adjusted for important socio-demographic and clinico-pathological factors were applied to assess the association of genetic polymorphisms with overall survival (OS) and progression-free survival (PFS). Significantly associated polymorphisms were then validated in an independent cohort of 137 esophageal adenocarcinoma patients. Among the 231 discovery cohort patients, 86% were male, median diagnosis age was 64 years, 34% were metastatic at diagnosis and median OS and PFS were 20 and 12 months, respectively. KDR rs17709898 was found significantly associated with PFS (adjusted hazard ratio, aHR = 0.69, 95% confidence interval (CI): 0.53-0.90; P = 5.9E-3). FLT1 rs3794405 and rs678714 were significantly associated with OS (aHR = 1.44, 95% CI: 1.04-1.99; P = 0.03 and aHR = 1.50, 95% CI: 1.01-2.24; P = 0.045, respectively). No VEGFA polymorphisms were found significantly associated with either outcome. Upon validation, FLT1 rs3794405 remained strongly associated with OS (aHR = 1.59, 95% CI: 1.04-2.44; P = 0.03). FLT1 rs3794405 is significantly associated with OS in esophageal adenocarcinoma, whereby each variant allele confers a 45-60% increased risk of mortality. Validation and evaluation of this association in other cancer sites are warranted.


Assuntos
Adenocarcinoma/genética , Neoplasias Esofágicas/genética , Neovascularização Patológica/genética , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Estudos Prospectivos , Inquéritos e Questionários
16.
Acc Chem Res ; 47(2): 308-18, 2014 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-24341353

RESUMO

Because many physical and chemical processes occur at surfaces, surface atomic structure is a critical factor affecting the properties of materials. Due to the presence of high-density atomic steps and edges and abundant unsaturated coordination sites, micro- and nanocrystallites with high-energy surfaces usually exhibit greater reactivity than those with low-energy surfaces. However, high-energy crystal surfaces are usually lost during crystal growth as the total surface energy is minimized. Therefore, the selective exposure of high-energy facets at the surface of micro- and nanocrystallites is an important and challenging research topic. Metal oxides play important roles in surface-associated applications, including catalysis, gas sensing, luminescence, and antibiosis. The synthesis of metal oxide micro- and nanocrystallites with specific surfaces, particularly those with high surface energies, is more challenging than the synthesis of metal crystals due to the presence of strong metal-oxygen bonds and diverse crystal structures. In this Account, we briefly summarize recent progress in the surface-structure-controlled synthesis of several typical metal oxide micro- and nanocrystallites, including wurtzite ZnO, anatase TiO2, rutile SnO2, and rocksalt-type metal oxides. We also discuss the improvement of surface properties, focusing on high-energy surfaces. Because of the huge quantity and diverse structure of metal oxides, this Account is not intended to be comprehensive. Instead, we discuss salient features of metal oxide micro- and nanocrystallites using examples primarily from our group. We first discuss general strategies for tuning the surface structure of metal oxide micro- and nanocrystallites, presenting several typical examples. For each example, we describe the basic crystallographic characteristics as well as the thermodynamic (i.e., tuning surface energy) or kinetic (i.e., tuning reaction rates) strategies we have used to synthesize micro- and nanocrystallites with high surface energies. We discuss the structural features of the specific facets and analyze the basis for the enhanced performance of the metal oxide micro- and nanocrystallites in water splitting, the degradation of organic pollutants, gas sensing, catalysis, luminescence, and antibiosis. Finally, we note the future trends in high-energy-facet metal oxide micro- and nanocrystallite research. A comprehensive understanding of the properties of metal oxide micro- and nanocrystallites with high-energy crystal surfaces and related synthetic strategies will facilitate the rational design of functional nanomaterials with desired characteristics.


Assuntos
Nanopartículas Metálicas/química , Nanotecnologia/métodos , Óxidos/química , Catálise , Poluentes Ambientais/química , Cinética , Propriedades de Superfície , Termodinâmica , Titânio/química , Óxido de Zinco/química
17.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 40(3): 317-25, 2015 Mar.
Artigo em Zh | MEDLINE | ID: mdl-25832524

RESUMO

OBJECTIVE: To assess the effect of premolar extractions on third molar angulation changes in orthodontic patients. METHODS: The Cochrane library, PubMed, Embase, China Science and Technology Periodical Database, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM) and Wanfang database were searched from January 1, 1990 to May 20, 2014 to identify all the studies about third molar angulation changes in orthodontic patients with or without premolars extraction, which was assigned as a extraction group and a control group. Th e extraction group was further divided into a fi rst premolar extraction subgroup and a second premolar extraction subgroup. Literature filtering, data extraction and methodological quality evaluation were finished independently by two researchers. After cross checking, the disagreements were solved by discussion. Meta-analysis was carried out by RevMan 5.3.3 software. RESULTS: Ten studies involving 712 patients were included. Meta-analysis revealed that: compared with the control group, the changes of third molar angulation in maxillary and mandible in the extraction group were statistically significantly different (all P<0.05); the difference in angulation between the two groups was about 5.19° in maxillary and 3.55° in mandibul. As for the premolar extraction subgroups, there was no significant difference in mandibular third molar angulation between them (P>0.05). CONCLUSION: The orthodontic treatment involving first or second premolar extractions can improve the maxillary third molar angulation, and the second premolar extraction is the best option.


Assuntos
Dente Pré-Molar , Dente Serotino , Extração Dentária , Povo Asiático , China , Humanos , Mandíbula , Maxila
18.
Chemistry ; 20(9): 2637-45, 2014 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-24449437

RESUMO

Elucidating the facet-dependent photocatalytic activity of semiconductor photocatalysts is important in improving the overall efficiency of photocatalysis. Furthermore, combining facet control with selective deposition of oxidation and/or reduction cocatalysts on specific faces of semiconductor photocatalysts is potentially an effective strategy to synergistically optimize the functionality of photocatalysts. In the present study, high-purity wurtzite-type ß-AgI platelet microcrystals with polar {0001} facets were prepared by a facile polyvinylpyrrolidone-assisted precipitation reaction. The polar-faceted AgI microplates were used as archetypes to demonstrate preferential diametric migration (i.e., effective separation) of photogenerated electrons and holes along the c axis. Such vectorial electron-hole separation stems from the asymmetric surface structures, which give rise to distinct photoexcited reaction behaviors on the ±(0001) polar facets of wurtzite-type semiconductors. Furthermore, on selective deposition of Ag and MnOx (1.5

19.
Chemistry ; 20(18): 5244-52, 2014 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-24677426

RESUMO

Surface functionalization of inorganic nanomaterials through chemical binding of organic ligands on the surface unsaturated atoms, forming unique organic-inorganic interfaces, is a powerful approach for creating special functions for inorganic nanomaterials. Herein, we report the synthesis of hierarchical MgO nanocrystal clusters (NCs) with an organic-inorganic interface induced multi-fluorescence and their application as new alternative labels for cellular imaging. The synthetic method was established by a dissolution and regrowth process with the assistance of carboxylic acid, in which the as-prepared MgO NCs were modified with carboxylic groups at the coordinatively unsaturated atoms of the surface. By introducing acetic acid to partially replace oleic acid in the reaction, the optical absorption of the produced MgO NCs was progressively engineered from the UV to the visible region. Importantly, with wider and continuous absorption profile, those MgO NCs presented bright and tunable multicolor emissions from blue-violet to green and yellow, with the highest absolute quantum yield up to (33±1) %. The overlap for the energy levels of the inorganic-organic interface and low-coordinated states stimulated a unique fluorescence resonance energy transfer phenomenon. Considering the potential application in cellular imaging, such multi-fluorescent MgO NCs were further encapsulated with a silica shell to improve the water solubility and stability. As expected, the as-formed MgO@SiO2 NCs possessed great biocompatibility and high performance in cellular imaging.


Assuntos
Corantes Fluorescentes/química , Compostos de Manganês/química , Nanopartículas/química , Óxidos/química , Ácidos Carboxílicos/química , Transferência Ressonante de Energia de Fluorescência , Células HeLa , Humanos , Nanopartículas/ultraestrutura , Imagem Óptica , Dióxido de Silício/química , Solubilidade , Propriedades de Superfície
20.
Adv Sci (Weinh) ; 11(11): e2306911, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38196300

RESUMO

Metal-organic frameworks (MOF) derived nitrogen-doped carbon-supported monodisperse Fe (Fe-N-C) catalysts are intensively studied, but great challenges remain in understanding the relationship between the coordination structure and the performance of Fe-N-C nanozymes. Herein, a novel nanocluster ligand-bridging strategy is proposed for constructing Fe-S1 N4 structures with axially coordinated S and Au nanoclusters on ZIF-8 derived Fe-N-C (labeled Aux /Fe-S1 N4 -C). The axial Au nanoclusters facilitate electron transfer to Fe active sites, utilizing the bridging ligand S as a medium, thereby enhancing the oxygen adsorption capacity of composite nanozymes. Compared to Fe-N-C, Aux /Fe-S1 N4 -C exhibits high oxidase-like specificity and activity, and holds great potential for detecting acetylcholinesterase activity with a detection limit of 5.1 µU mL-1 , surpassing most reported nanozymes.


Assuntos
Ouro , Oxirredutases , Acetilcolinesterase , Ouro/química , Ligantes
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