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1.
J Phys Chem Lett ; 15(23): 6108-6114, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38829304

RESUMO

Two-dimensional metal-organic networks (2D MONs) having heterogeneous coordination nodes (HCNs) could exhibit excellent performance in catalysis and optoelectronics because of the unbalanced electron distribution of the coordinating metals. Therefore, the design and construction of 2D MONs with HCNs are highly desirable but remain challenging. Here, we report the construction of 2D organometallic coordination networks with an organic Kagome lattice and a semiregular metal lattice on Au(111) via the in situ formation of HCNs. Using a bifunctional precursor 1,4-dibromo-2,5-diisocyanobenzene, the coordination of isocyano with Au adatom on a room-temperature Au(111) yielded metal-organic coordination chains with isocyano-Au-isocyano nodes. In contrast, on a high-temperature Au(111), a selective debromination/coordination cascade reaction occurred, affording 2D organometallic coordination networks with phenyl-Au-isocyano nodes. By combining scanning tunneling microscopy and density functional theory calculations, we determined the structures of coordination products and the nature of coordination nodes, demonstrating a thermodynamically favorable pathway for forming the phenyl-Au-isocyano nodes.

2.
Angew Chem Int Ed Engl ; 63(11): e202318142, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38265124

RESUMO

Precisely introducing topological defects is an important strategy in nanographene crystal engineering because defects can tune π-electronic structures and control molecular assemblies. The synergistic control of the synthesis and assembly of nanographenes by embedding the topological defects to afford two-dimensional (2D) crystals on surfaces is still a great challenge. By in-situ embedding ladder bipyrazinylene (LBPy) into acene, the narrowest nanographene with zigzag edges, we have achieved the precise preparation of 2D nonbenzenoid heteroacene crystals on Au(111). Through intramolecular electrocyclization of o-diisocyanides and Au adatom-directed [2+2] cycloaddition, the nonbenzenoid heteroacene products are produced with high chemoselectivity, and lead to the molecular 2D assembly via LBPy-derived interlocking hydrogen bonds. Using bond-resolved scanning tunneling microscopy, we determined the atomic structures of the nonbenzenoid heteroacene product and diverse organometallic intermediates. The tunneling spectroscopy measurements revealed the electronic structure of the nonbenzenoid heteroacene, which is supported by density functional theory (DFT) calculations. The observed distinct organometallic intermediates during progression annealing combined with DFT calculations demonstrated that LBPy formation proceeds via electrocyclization of o-diisocyanides, trapping of heteroarynes by Au adatoms, and stepwise elimination of Au adatoms.

3.
J Am Chem Soc ; 145(24): 13048-13058, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37289993

RESUMO

Two-dimensional (2D) crystal-to-crystal transition is an important method in crystal engineering because of its ability to directly create diverse crystal materials from one crystal. However, steering a 2D single-layer crystal-to-crystal transition on surfaces with high chemo- and stereoselectivity under ultra-high vacuum conditions is a great challenge because the transition is a complex dynamic process. Here, we report a highly chemoselective 2D crystal transition from radialene to cumulene with retention of stereoselectivity on Ag(111) via retro-[2 + 1] cycloaddition of three-membered carbon rings and directly visualize the transition process involving a stepwise epitaxial growth mechanism by the combination of scanning tunneling microscopy and non-contact atomic force microscopy. Using progression annealing, we found that isocyanides on Ag(111) at a low annealing temperature underwent sequential [1 + 1 + 1] cycloaddition and enantioselective molecular recognition based on C-H···Cl hydrogen bonding interactions to form 2D triaza[3]radialene crystals. In contrast, a higher annealing temperature induced the transformation of triaza[3]radialenes to generate trans-diaza[3]cumulenes, which were further assembled into 2D cumulene-based crystals through twofold N-Ag-N coordination and C-H···Cl hydrogen bonding interactions. By combining the observed distinct transient intermediates and density functional theory calculations, we demonstrate that the retro-[2 + 1] cycloaddition reaction proceeds via the ring opening of a three-membered carbon ring, sequential dechlorination/hydrogen passivation, and deisocyanation. Our findings provide new insights into the growth mechanism and dynamics of 2D crystals and have implications for controllable crystal engineering.

4.
Materials (Basel) ; 16(8)2023 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-37109975

RESUMO

The thickness debit effect of creep behavior has been a focal point of nickel-based single-crystal superalloy research, and there is a need for an advanced creep deformation measurement method. This study developed a novel high-temperature creep test system based on a single-camera stereo digital image correlation (DIC) method with four plane mirrors to conduct creep tests on thin-walled specimens of a nickel-based single-crystal alloy, DD6, with thicknesses of 0.6 mm and 1.2 mm under experimental conditions of 980 °C/250 MPa. The reliability of the single-camera stereo DIC method in measuring long-term deformation at a high temperature was experimentally verified. The experimental results show that the creep life of the thinner specimen was significantly shorter. It was found the lack of coordination in the creep deformation process of the edge and middle section of the thin-walled specimens may be an important factor in the thickness debit effect according to the full-field strain contour. By comparing the local strain curve at the rupture point with the average creep strain curve, it was found that the creep rate at the rupture point was less affected by the specimen thickness during the secondary creep stage, while the average creep rate in the working section significantly increased as the wall thickness decreased. The thicker specimen usually had a higher average rupture strain and higher damage tolerance, which prolonged the rupture time.

5.
J Am Chem Soc ; 145(13): 7136-7146, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-36951172

RESUMO

The emergence of quantum magnetism in nanographenes provides ample opportunities to fabricate purely organic devices for spintronics and quantum information. Although heteroatom doping is a viable way to engineer the electronic properties of nanographenes, the synthesis of doped nanographenes with collective quantum magnetism remains elusive. Here, a set of nitrogen-doped nanographenes (N-NGs) with atomic precision are fabricated on Au(111) through a combination of imidazole [2+2+2]-cyclotrimerization and cyclodehydrogenation reactions. High-resolution scanning probe microscopy measurements reveal the presence of collective quantum magnetism for nanographenes with three radicals, with spectroscopic features which cannot be captured by mean-field density functional theory calculations but can be well reproduced by Heisenberg spin model calculations. In addition, the mechanism of magnetic exchange interaction of N-NGs has been revealed and compared with their counterparts with pure hydrocarbons. Our findings demonstrate the bottom-up synthesis of atomically precise N-NGs which can be utilized to fabricate low-dimensional extended graphene nanostructures for realizing ordered quantum phases.

6.
J Phys Chem Lett ; 13(45): 10589-10596, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36346870

RESUMO

Dendronized polymers (DPs) consist of a linear polymeric backbone with dendritic side chains. Fine-tuning of the functional groups in the side chains enriches the structural versatility of the DPs and imparts a variety of novel physical properties. Herein, the first on-surface synthesis of DPs is achieved via the postfunctionalization of polymers on Au(111), in which the surface-confinement-induced planar conformation and chiral configurations were unambiguously characterized. While the dendronized monomer was synthesized in situ on Au(111), the subsequent polymerization afforded only short, cross-linked DP chains owing to multiple side reactions. The postfunctionalization approach selectively produced brominated polyphenylene backbone moieties by the deiodination polymerization of 4-bromo-4″-iodo-5'-(4-iodophenyl)-1,1':3',1″-terphenyl on Au(111), which smoothly underwent divergent cross-coupling reactions with two different isocyanides to form two types of DPs as individual long chains.

7.
Angew Chem Int Ed Engl ; 61(15): e202117714, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35179282

RESUMO

[3]Radialenes are the smallest carbocyclic structures with unusual topologies and cross-conjugated π-electronic structures. Here, we report a novel [1+1+1] cycloaddition reaction for the synthesis of aza[3]radialenes on the Ag(111) surface, where the steric hindrance of the chlorine substituents guides the selective and orientational assembling of the isocyanide precursors. By combining scanning tunneling microscopy, non-contact atomic force microscopy, and time-of-flight secondary ion mass spectrometry, we determined the atomic structure of the produced aza[3]radialenes. Furthermore, two reaction pathways including synergistic and stepwise are proposed based on density functional theory calculations, which reveal the role of the chlorine substituents in the activation of the isocyano groups via electrostatic interaction.

8.
J Leukoc Biol ; 112(2): 299-311, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34927743

RESUMO

The stromal niche plays a pivotal role in AML chemoresistance and energy metabolism reprogramming is a hallmark of a tumor. 5'-Adenosine monophosphate-activated protein kinase (AMPK) is an important energy sensor suppressing mammalian target of rapamycin complex 1 (mTORC1) activity. However, the role of AMPK-mTORC1 pathway on connecting AML cell energy metabolism reprogramming and chemoresistance induced by the bone marrow microenvironment (BMM) is not defined. Here, with a co-culture system that simulates the interaction between BMM and AML cells, it is shown that stromal contact led to a decreased sensitivity to chemotherapy accompanied by an increase of oxidative phosphorylation (OXPHOS) activity and mitochondrial ATP synthesis in AML cells. The increased OXPHOS activity and excessive ATP production promoted chemoresistance of AML cells through inhibiting AMPK activity and in turn activating mTORC1 activity. In an in vivo AML mouse model, depletion of AMPK activity with genetic targeting promoted AML progression and reduced their sensitivity to chemotherapeutic drugs. Collectively, AML cells' acquired increased OXPHOS activity as well as AMPK inhibition could be therapeutically exploited in an effort to overcome BMM-mediated chemoresistance.


Assuntos
Leucemia Mieloide Aguda , Fosforilação Oxidativa , Proteínas Quinases Ativadas por AMP/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Medula Óssea/patologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Microambiente Tumoral
9.
ACS Nano ; 15(11): 18014-18022, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34677047

RESUMO

Molecular adsorption conformations and arrangement configurations on surfaces are important structural aspects of surface stereochemistry, but their roles in steering the structures of metal-organic networks (MONs) remain vague and unexplored. In this study, we constructed MONs by the coordination self-assembly of isocyanides on Cu(111) and Ag(111) surfaces and demonstrated that the MON structures can be steered by surface stereochemistry, including the adsorption conformations of the isocyanide molecules and the arrangement configurations of the coordination nodes and subunits. The coordination self-assembly of 1,4-phenylene diisocyanobenzene afforded a honeycomb MON consisting of 3-fold (isocyano)3-Cu motifs on a Cu(111) surface. In contrast, geometrically different chevron-shaped 1,3-phenylene diisocyanobenzene (m-DICB) failed to generate a MON, which is ascribable to its standing conformation on the Cu(111) surface. However, m-DICB was adsorbed in a flat conformation on a Ag(111) surface, which has a larger lattice constant than a Cu(111) surface, and smoothly underwent coordination self-assembly to form a MON consisting of (isocyano)3-Ag motifs. Interestingly, only C3-Ag nodes with heterotactic configurations could grow into larger subunits; those subunits with heterotactic configurations further grew into Sierpinski triangle fractals (up to fourth order), while subunits with homotactic configurations afforded a triangular MON.

10.
J Med Biochem ; 40(1): 86-91, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33584144

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) affects human health worldwide. Our objective was to explore the correlation between urinary retinol-binding protein (URBP) and NAFLD. METHODS: This cross-sectional study included 445 NAFLD patients and 911 healthy controls. The URBP level and other parameters were measured. RESULTS: The URBP level (expressed by the RBP/creatinine ratio) was higher in the NAFLD patients compared with the non-NAFLD patients. The urinary RBP/creatinine ratio was an independent risk factor for NAFLD after univariate and multivariate regression analysis, with the or values of 2.271 (1.795-2.872, P < 0.001) and 2.338 (1.775-3.080, P < 0.001), respectively. The prevalence of the urinary RBP/creatinine ratio (groups 1, 2, 3, 4) was 20.0%, 17.3%, 27.3%, and 35.4%, respectively (P < 0.001), and the prevalence of NAFLD in the high urinary RBP/creatinine ratio group was significantly higher than that in the low urinary RBP/creatinine ratio group. CONCLUSIONS: Our results revealed that the urinary RBP/creatinine ratio was an independent risk factor for NAFLD.

11.
Biomed Pharmacother ; 117: 109018, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31176166

RESUMO

AIM: Melatonin shows therapeutic benefits in gastric cancer, but the mechanism underlying its anticancer effects remains elusive. The aim of this study was to determine whether melatonin inhibits lung metastasis in gastric cancer. MAIN METHODS: A lung metastasis model of gastric cancer was established in nude mice injected with human gastric adenocarcinoma MGC80-3 cells. Mice were divided into control, IL-1ß-treated, melatonin-treated, and IL-1ß plus melatonin-treated groups and analyzed for the formation of lung metastatic nodules by flow cytometry and hematoxylin and eosin staining. The mRNA expression of epithelial-mesenchymal transition (EMT) markers was assessed by RT-qPCR. The activities of matrix metalloproteinase (MMP)-2 and MMP-9 were determined by gelatin zymography and their protein expression by western blotting and immunohistochemistry. The levels of NF-κB p65 and phosphorylated (p)-p65 were detected by immunohistochemistry. KEY FINDINGS: The number of lung metastases in the IL-1ß plus melatonin group was significantly lower and the sizes of nodules were smaller than those in the IL-1ß group. Furthermore, melatonin reversed changes in the expression of EMT markers induced by IL-1ß by increasing mRNA levels of ß-catenin and E-cadherin and decreasing those of fibronectin, vimentin, and Snail compared to IL-1ß. Treatment with IL-1ß upregulated the expression and activities of MMP-2 and MMP-9 and expression of NF-κB p65 and phospho-p65 (p-p65), but melatonin alleviated these effects. SIGNIFICANCE: Melatonin inhibited IL-1ß-induced lung metastasis of gastric cancer through downregulation of MMP-2, MMP-9, and NF-κB p65 expression and activities. These findings provide a basis for potential use of melatonin as a supplementary therapy for patients with advanced gastric cancer.


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Melatonina/uso terapêutico , Neoplasias Gástricas/patologia , Animais , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-1beta/metabolismo , Neoplasias Pulmonares/genética , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Melatonina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/metabolismo
12.
Int J Legal Med ; 133(1): 95-97, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29779152

RESUMO

A total of 39 Y-chromosomal short tandem repeat (Y-STR) loci included in the advanced commercial six-dye multiplex system (AGCU Database Y30 kit) and a custom-designed four-dye multiplex system were investigated in 259 unrelated healthy Chinese males residing in Henan Province, central China. The haplotype diversity (HD) values were 0.99997 and 1.0000 for the six and four fluorescent-multiplex amplification systems, respectively. The discrimination capacity (DC) values were 0.9961 and 1.0000, respectively. When the 39 Y-STR loci were considered, 259 unique haplotypes were obtained in Henan Han individuals with both the haplotype diversity and discrimination capacity being 1.000. The gene diversity (GD) of 39 Y-STR loci in the studied group ranged from 0.3956 (DYS588) to 0.9990 (DYF403S1). Population comparisons between the Henan Han and 24 reference groups were performed. Both multidimensional scaling plots and phylogenetic analysis demonstrated that significant genetic differences existed between Henan Han and reference ethnic minorities of China, particularly the Tibetan, Uighur, and Mongolian populations. Moreover, the results indicated that 39 Y-STRs included in the two fluorescent-multiplex amplification systems are highly polymorphic and informative in the studied populations and can be employed as complementary tools for forensic application and human genetics research.


Assuntos
Cromossomos Humanos Y , Etnicidade/genética , Repetições de Microssatélites , China , Impressões Digitais de DNA , Frequência do Gene , Genética Populacional , Haplótipos , Humanos , Masculino , Polimorfismo Genético
13.
Clin Lab ; 64(10): 1655-1660, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30336528

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) can cause renal injury, and urinary transferrin (UTRF) is extremely sensitive to renal injury. We aimed to investigate the correlation between UTRF and NAFLD and to observe the distribution of NAFLD at different levels of UTRF. METHODS: A total of 711 subjects fulfilled the diagnostic criteria of NAFLD and 1,396 healthy control participants were enrolled in this study. UTRF levels and other clinical and laboratory parameters were measured. RESULTS: The UTRF level was higher in NAFLD than in non-NAFLD patients. Unit and multiple regression analysis showed that UTRF was an independent risk factor for NAFLD, with OR values of 1.474 (1.328 - 1.635, p < 0.001) and 1.435 (1.267 - 1.625, p < 0.001), respectively. The prevalence of UTRF (groups 1, 2, 3, 4) was 25.61%, 26.56%, 38.14%, and 44.59%, respectively (p < 0.001), and the prevalence of NAFLD in the high UTRF group was significantly higher than in the low UTRF group. CONCLUSIONS: UTRF is an independent risk factor for NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica/urina , Transferrina/urina , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Fatores de Risco
14.
Parasit Vectors ; 11(1): 124, 2018 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-29499747

RESUMO

BACKGROUND: Trichomonas vaginalis (TV) is a protozoan parasite that causes trichomoniasis, a sexually transmitted disease, worldwide. In this study, we investigated the prevalence and genetic characterization of T. vaginalis and contrasted the most prevalent strains of T. vaginalis isolated from Xinxiang City, Henan Province, China. RESULTS: In Xinxiang from September 2015 to September 2017, a total of 267 (1.64%, 95% confidence interval, CI: 1.45-1.85) clinical T. vaginalis-positive samples from vaginal secretions were observed by wet mount microscopy from 16,294 women with some clinical symptoms of trichomoniasis. We found that trichomoniasis frequently occurred in the 21- to 40-year-old age group and in winter. After the 267 clinical T. vaginalis positive samples were cultured, 68 isolates of T. vaginalis were harvested and identified as genotype E (58.82%), H (17.65%), mixed 1 (17.65%) and mixed 2 (5.88%) using a sensitive and reliable polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) typing method on the actin gene. The phylogenetic diversity analysis showed that the genotype E samples fell within a separate clade compared to the other T. vaginalis isolates, while the samples of the genotype H separated into two clades. CONCLUSIONS: Our results demonstrate a notable gene polymorphism of clinical isolates from the targeted population and provide insight into the performance of these genetic markers in the molecular epidemiology of trichomoniasis. However, further studies are needed to clarify the association between a certain genotype and the pathogenicity of T. vaginalis.


Assuntos
Variação Genética , Trichomonas vaginalis/genética , Trichomonas vaginalis/isolamento & purificação , Vagina/parasitologia , Adolescente , Adulto , China/epidemiologia , DNA de Protozoário/genética , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Filogenia , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Prevalência , Infecções Sexualmente Transmissíveis , Tricomoníase/epidemiologia , Tricomoníase/parasitologia , Trichomonas vaginalis/classificação , Adulto Jovem
15.
J Immunol ; 199(7): 2475-2482, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28821586

RESUMO

Human T lymphotropic virus type 1 (HTLV-1) belongs to the deltaretrovirus family and has been linked to multiple diseases. However, the innate host defense against HTLV-1 is unclear. In this study, we report that the expression of Ku70, a known DNA sensor against DNA viruses, could be induced by HTLV-1 infection in HeLa, PMA-differentiated THP1 cells, primary human monocytes, and human monocyte-derived macrophages. In these cells, the overexpression of Ku70 inhibited the HTLV-1 protein expression, whereas the knockdown of Ku70 promoted the HTLV-1 protein expression. Furthermore, the overexpression of Ku70 enhanced the cellular response to HTLV-1 infection, whereas Ku70 knockdown yielded the opposite effect. Additionally, Ku70 was found to interact with HTLV-1 reverse transcription intermediate ssDNA90. ssDNA90 stimulation induced Ku70 expression and Ku70 promoted ssDNA90-triggered innate immune responses. Finally, HTLV-1 infection enhanced the association between Ku70 and stimulator of IFN genes, suggesting that stimulator of IFN genes was involved in Ku70-mediated host defenses against HTLV-1 infection. Taken together, our findings suggest a new sensor that detects HTLV-1 reverse transcription intermediate and controls HTLV-1 replication. These findings may provide new angles to understand host defenses against HTLV-1 infection and HTLV-1-associated diseases.


Assuntos
DNA Viral , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Autoantígeno Ku/genética , Autoantígeno Ku/metabolismo , Replicação Viral , Células Cultivadas , Produtos do Gene tax/genética , Células HeLa , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Imunidade Inata , Interferons/genética , Interferons/imunologia , Autoantígeno Ku/deficiência , Autoantígeno Ku/imunologia , Macrófagos/virologia , Monócitos/virologia , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética
16.
Mol Biosyst ; 13(9): 1817-1826, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28714505

RESUMO

The bioactivity of drugs is attributed to their interaction with biological molecules, embodied in either their direct or indirect influence on enzyme activity and conformation. Di-2-pyridylketone hydrazine dithiocarbamate (DpdtC) exhibits significant antitumor activity in our preliminary study. We speculated that its activity may partly stem from enzyme inhibition due to strong metal chelating ability. To this end, we assessed its effect on catalase from erythrocytes and found evidence of inhibition, which was further confirmed by ROS determination in vivo. Thus, detailing the interaction between the agent and catalase via spectroscopic methods and molecular docking was required to obtain information on both the dynamics and thermodynamic parameters. The Lineweaver-Burk plot implied an uncompetitive pattern between DpdtC and catalase from beef liver, and IC50 = ∼7 µM. The thermodynamic parameters from fluorescence quenching measurements indicated that DpdtC could bind to catalase with moderate affinity (Ka = approximately 104 M-1). CD spectra revealed that DpdtC could significantly disrupt the secondary structure of catalase. Docking studies indicated that DpdtC bound to a flexible region of catalase, involving hydrogen bonds and salt bond; this was consistent with thermodynamic results from spectral investigations. Our data clearly showed that catalase inhibition of DpdtC was not due to direct chelation of iron from heme (killing), but through an allosteric effect. Thus, it can be concluded that the antiproliferative activity of DpdtC is partially attributed to its catalase inhibition.


Assuntos
Catalase/antagonistas & inibidores , Catalase/química , Pirazóis/química , Tiocarbamatos/química , Tiocarbamatos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dicroísmo Circular , Ativação Enzimática/efeitos dos fármacos , Humanos , Cinética , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade
17.
J Huazhong Univ Sci Technolog Med Sci ; 35(5): 781-784, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26489639

RESUMO

In this study, we conducted an investigation among medical workers, patients and college students concerning their acceptability of breast palpation performed by male doctors (hereinafter referred to as "acceptability", or "the examination", respectively, if not otherwise indicated), to get the information about their acceptability and reasons for accepting or declining the examination among the three population. A questionnaire investigation was conducted in 500 patients with breast diseases, 700 students of medical colleges, and 280 medical workers working in hospitals. The subjects were asked to choose between two options: accept or do not accept (the examination). The subjects were asked to fill out the questionnaire forms on free and anonymous basis and the questionnaire forms were collected on spot, immediately after completion. The questionnaires collected were coded, sorted out and checked. Data of the eligible questionnaires were input into Epidata software and analyzed by SPSS. Upon the establishment of the database, the intra-group data were tested by utilizing χ(2) test. Among 1480 questionnaires, 1293 (90.41%) questionnaires were retrieved. Our results showed that 56.78% of patients reported that they could accept breast palpation by male doctors. About 59.66% of medical staff expressed their acceptance of the examination, but only 35.03% of students said the examination. On the basis of this study, we were led to conclude that the examination is not well accepted by different populations, and therefore, (1) medical professionals and administrators should pay attention to the gender-related ethics in their practice and the feeling of patients should be respected when medical examinations involve private or sensitive body parts; (2) to this end, related departments should be properly staffed with doctors of both sexes, and this is especially true of the departments involving the examination or treatment of private or sensitive body parts; (3) health education should, among other things, include helping female patients to overcome the fear and anxiety in such examinations. This is of great importance since some women may miss the opportunity to get timely diagnosis.


Assuntos
Pessoal de Saúde/psicologia , Pacientes Ambulatoriais/psicologia , Palpação/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Exame Físico/ética , Estudantes de Medicina/psicologia , Adulto , Povo Asiático , Feminino , Humanos , Masculino , Glândulas Mamárias Humanas/fisiologia , Glândulas Mamárias Humanas/fisiopatologia , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Médicos/ética , Inquéritos e Questionários
18.
Int J Mol Sci ; 16(2): 3335-49, 2015 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-25654229

RESUMO

EcR (ecdysone receptor)-mediated ecdysone signaling pathway contributes to regulate the transcription of genes involved in various processes during insect development. In this work, we detected the expression of EcR gene in silkworm ovary-derived BmN4 cells and found that EcR RNAi result in an alteration of cell shape, indicating that EcR may orchestrate cell cycle progression. EcR RNAi and EcR overexpression analysis revealed that in the cultured BmN4 cells, EcR respectively promoted and suppressed the transcription of E2F-1 and CycE, two genes controlling cell cycle progression. Further examination demonstrated that ecdysone application in BmN4 cells not only changed the transcription of these two cell cycle genes like that under EcR overexpression, but also induced cell cycle arrest at G2/M phase. In vivo analysis confirmed that E2F-1 expression was elevated in silk gland of silkworm larvae after ecdysone application, which is same as its response to ecdysone in BmN4 cells. However, ecdysone also promotes CycE transcription in silk gland, and this is converse with the observation in BmN4 cells. These results provide new insights into understanding the roles of EcR-mediated ecdysone signaling in the regulation of cell cycle.


Assuntos
Bombyx/genética , Proteínas de Ciclo Celular/genética , Regulação da Expressão Gênica , Receptores de Esteroides/metabolismo , Transcrição Gênica , Animais , Bombyx/efeitos dos fármacos , Bombyx/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular , Relação Dose-Resposta a Droga , Ecdisona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Interferência de RNA , Receptores de Esteroides/genética
19.
Iran J Public Health ; 44(12): 1603-12, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26811811

RESUMO

BACKGROUND: We aimed to evaluate the levels of social support in patients with postoperative esophageal carcinoma and potential effect of social support on generic and EC-specific quality of life. METHODS: Overall, 803 Chinese patients with EC were recruited in the high-incidence region- Linzhou in Henan, China for the observation study. We obtained data on European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), disease-specific score of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-OES18 (The QLQ-OES18), and social support evaluation score at home visits by a specially trained research team. RESULTS: Aging and low education were negatively predicted total social support scores. A significant correlation (P = 0.000, 9 = 0.000) was found between QOL physical function and either the subjective or the objective dimensions in social supportive system. OES18 eating difficulty was significantly associated with objective support including family intimacy, friendship and community support (P = 0.016, P = 0.001). CONCLUSIONS: The social support team should endorse quality care as integrating community-care management in post-esophagus recovery and meet the need of individual health quality of life. The elders, educational levels and rural farmers are significant to challenge the social supportive delivery in the current model of esophagus cancer care.

20.
PLoS One ; 9(10): e109111, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25280016

RESUMO

The transcription factor Broad Complex (BR-C) is an early ecdysone response gene in insects and contains two types of domains: two zinc finger domains for the activation of gene transcription and a Bric-a-brac/Tramtrack/Broad complex (BTB) domain for protein-protein interaction. Although the mechanism of zinc finger-mediated gene transcription is well studied, the partners interacting with the BTB domain of BR-C has not been elucidated until now. Here, we performed a yeast two-hybrid screen using the BTB domain of silkworm BR-C as bait and identified the receptor for activated C-kinase 1 (RACK1), a scaffolding/anchoring protein, as the novel partner capable of interacting with BR-C. The interaction between BR-C and RACK1 was further confirmed by far-western blotting and pull-down assays. Importantly, the disruption of this interaction, via RNAi against the endogenous RACK1 gene or deletion of the BTB domain, abolished the nuclear import of BR-C in BmN4 cells. In addition, RNAi against the endogenous PKC gene as well as phosphorylation-deficient mutation of the predicted PKC phosphorylation sites at either Ser373 or Thr406 in BR-C phenocopied RACK1 RNAi and altered the nuclear localization of BR-C. However, when BTB domain was deleted, phosphorylation mimics of either Ser373 or Thr406 had no effect on the nuclear import of BR-C. Moreover, mutating the PKC phosphorylation sites at Ser373 and Thr406 or deleting the BTB domain significantly decreased the transcriptional activation of a BR-C target gene. Given that RACK1 is necessary for recruiting PKC to close and phosphorylate target proteins, we suggest that the PKC-mediated phosphorylation and nuclear import of BR-C is determined by its interaction with RACK1. This novel finding will be helpful for further deciphering the mechanism underlying the role of BR-C proteins during insect development.


Assuntos
Bombyx/metabolismo , Regulação da Expressão Gênica , Receptores de Superfície Celular/fisiologia , Fatores de Transcrição/fisiologia , Animais , Sítios de Ligação , Linhagem Celular , Modelos Biológicos , Mutagênese Sítio-Dirigida , Fosforilação , Estrutura Terciária de Proteína , Interferência de RNA , Receptores de Quinase C Ativada , Receptores de Superfície Celular/análise , Receptores de Superfície Celular/genética , Fatores de Transcrição/análise , Fatores de Transcrição/genética , Técnicas do Sistema de Duplo-Híbrido
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