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1.
J Multidiscip Healthc ; 17: 609-617, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348208

RESUMO

Purpose: This study aimed to establish a stereoscopic neural learning network through deep learning and construct an artificial intelligence (AI) diagnosis system for the prediction of benign and malignant thyroid diseases, as well as repeatedly verified the diagnosis system and adjusted the data, in order to develop a type of AI-assisted thyroid diagnosis software with a low false negative rate and high sensitivity for clinical practice. Patients and Methods: From July 2020 to April 2023, A total of 36 patients with thyroid nodules in our hospital were selected for diagnosis of thyroid nodules based on the Expert Consensus on Thyroid Ultrasound; samples were taken by aspiration biopsy or surgically and sent for pathological diagnosis. The ultrasonic diagnosis results were compared with the pathological results, a database was established based on the ultrasonic diagnostic characteristics and was entered in the AI-assisted diagnosis software for judgment of benign and malignant conditions. The data in the software were corrected based on the conformity rate and the reasons for misjudgment, and the corrected software was used to evaluate the benign and malignant conditions of the 36 patients, until the conformity rate exceeded 90%. Results: The initial conformity rate of the AI software for identifying benign and malignant conditions was 88%, while that of the software utilizing the database was 94%. Conclusion: We established a stereoscopic neural learning network and construct an AI diagnosis system for the prediction of benign and malignant thyroid diseases, with a low false negative rate and high sensitivity for clinical practice.

2.
Langmuir ; 40(9): 4914-4926, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38385347

RESUMO

Electrochemical scanning tunneling microscopy (EC-STM) and electrochemical quartz crystal microbalance (E-QCM) techniques in combination with DFT calculations have been applied to reveal the static phase and the phase transition of copper underpotential deposition (UPD) on a gold electrode surface. EC-STM demonstrated, for the first time, the direct visualization of the disintegration of (√3 × âˆš3)R30° copper UPD adlayer with coadsorbed SO42- while changing sample potential (ES) toward the redox Pa2/Pc2 peaks, which are associated with the phase transition between the Cu UPD (√3 × âˆš3)R30° phase II and disordered randomly adsorbed phase III. DFT calculations show that SO42- binds via three oxygens to the bridge sites of the copper with sulfate being located directly above the copper vacancy in the (√3 × âˆš3)R30° adlayer, whereas the remaining oxygen of the sulfate points away from the surface. E-QCM measurement of the change of the electric charge due to Cu UPD Faradaic processes, the change of the interfacial mass due to the adsorption and desorption of Cu(II) and SO42-, and the formation and stripping of UPD copper on the gold surface provide complementary information that validates the EC-STM and DFT results. This work demonstrated the advantage of using complementary in situ experimental techniques (E-QCM and EC-STM) combined with simulations to obtain an accurate and complete picture of the dynamic interfacial adsorption and UPD processes at the electrode/electrolyte interface.

3.
Biochemistry ; 63(3): 312-325, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38271599

RESUMO

We report a thorough investigation of the role of single-stranded thymidine (ssT) linkers in the stability and flexibility of minimal, multistranded DNA nanostructures. We systematically explore the impact of varying the number of ssTs in three-way junction motifs (3WJs) on their formation and properties. Through various UV melting experiments and molecular dynamics simulations, we demonstrate that while the number of ssTs minimally affects thermodynamic stability, the increasing ssT regions significantly enhance the structural flexibility of 3WJs. Utilizing this knowledge, we design triangular DNA nanoparticles with varying ssTs, all showing exceptional assembly efficiency except for the 0T triangle. All triangles demonstrate enhanced stability in blood serum and are nonimmunostimulatory and nontoxic in mammalian cell lines. The 4T 3WJ is chosen as the building block for constructing other polygons due to its enhanced flexibility and favorable physicochemical characteristics, making it a versatile choice for creating cost-effective, stable, and functional DNA nanostructures that can be stored in the dehydrated forms while retaining their structures. Our study provides valuable insights into the design and application of nucleic acid nanostructures, emphasizing the importance of understanding stability and flexibility in the realm of nucleic acid nanotechnology. Our findings suggest the intricate connection between these ssTs and the structural adaptability of DNA 3WJs, paving the way for more precise design and engineering of nucleic acid nanosystems suitable for broad biomedical applications.


Assuntos
Nanopartículas , Nanoestruturas , Ácidos Nucleicos , Animais , Conformação de Ácido Nucleico , Nanoestruturas/química , Nanotecnologia , DNA/química , Nanopartículas/química , Mamíferos
4.
Eur J Med Chem ; 265: 116044, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38145603

RESUMO

Ferroptosis is a form of non-apoptotic cell death, regulated by phospholipid hydroperoxide glutathione peroxidase 4 (GPX4), a selenoprotein with a selenocysteine residue (sec) in the active site. GPX4 is a promising target for cancer cells in therapy-resistant conditions via ferroptosis, which can reduce the level of lipid reactive oxygen species (ROS). So far, all existing GPX4 inhibitors covalently bind to GPX4 via a reactive alkyl chloride moiety or masked nitrile-oxide electrophiles with poor selectivity and pharmacokinetic properties and most were obtained by cell phenotype-based screening. Lacking of effective high-throughput screening methods for GPX4 protein limits the discovery of GPX4 inhibitors. Here, we report a fluorescence polarization (FP)-based high throughput screening (HTS) assay for GPX4-U46C-C10A-C66A in vitro, and found Metamizole sodium from our in-house compound library inhibits GPX4-U46C-C10A-C66A enzyme activity. Structure-activity relationships (SAR) demonstrated the importance of sulfonyl group on interaction between Metamizole sodium and GPX4-U46C-C10A-C66A. Our FP assay could be an effective tool for discovery of GPX4 inhibitors and Metamizole sodium was a potential inhibitor for GPX4 in vitro.


Assuntos
Dipirona , Ensaios de Triagem em Larga Escala , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Selenocisteína/metabolismo , Relação Estrutura-Atividade , Glutationa Peroxidase/metabolismo
5.
Food Chem ; 424: 136360, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37207604

RESUMO

The application of rice and pea proteins in food production is limited due to their undesirable processing performance. The objective of this research was to develop a novel rice-pea protein gel using alkali-heat treatment. This gel had a higher solubility, stronger gel strength, better water retention capacity, and denser bilayer network. This is due to the alkali-heat induced modifications for the secondary structures of proteins (i.e., a decrease in the α-helix, and an increase in the ß-sheets) and the interactions between protein molecules. The network structure of gel was more compact by adding 2% and 4% alkali-heat rice protein (AH-RP). This resulted in a stable double-layer network structure of gel. Adding 4% AH-RP significantly improved the hardness and elasticity of gel. This gel will have a good potential use for being the ingredient to produce the functional foods and meat analogs.


Assuntos
Oryza , Proteínas de Ervilha , Manipulação de Alimentos/métodos , Oryza/química , Elasticidade , Dureza , Géis/química
6.
Nat Commun ; 14(1): 2025, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-37041152

RESUMO

The portal-scaffold complex is believed to nucleate the assembly of herpesvirus procapsids. During capsid maturation, two events occur: scaffold expulsion and DNA incorporation. The portal-scaffold interaction and the conformational changes that occur to the portal during the different stages of capsid formation have yet to be elucidated structurally. Here we present high-resolution structures of the A- and B-capsids and in-situ portals of human cytomegalovirus. We show that scaffolds bind to the hydrophobic cavities formed by the dimerization and Johnson-fold domains of the major capsid proteins. We further show that 12 loop-helix-loop fragments-presumably from the scaffold domain-insert into the hydrophobic pocket of the portal crown domain. The portal also undergoes significant changes both positionally and conformationally as it accompanies DNA packaging. These findings unravel the mechanism by which the portal interacts with the scaffold to nucleate capsid assembly and further our understanding of scaffold expulsion and DNA incorporation.


Assuntos
Capsídeo , Herpesvirus Humano 1 , Humanos , Capsídeo/metabolismo , Microscopia Crioeletrônica , Citomegalovirus/genética , Proteínas Virais/metabolismo , Herpesvirus Humano 1/genética , Montagem de Vírus/genética , Proteínas do Capsídeo/metabolismo , DNA/metabolismo
7.
J Clin Lab Anal ; 36(7): e24406, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35588431

RESUMO

BACKGROUND: LINC00941 has been proved to be related to various tumors, but its relationship with laryngocarcinoma remains vague. METHODS: LINC00941 expression in laryngocarcinoma tumor and laryngocarcinoma cells was determined by real time-quantitative polymerase chain reaction (RT-qPCR). Besides, the five-year survival of laryngocarcinoma patients with different LINC00941 expression was analyzed with Kaplan-Meier survival analysis, and the clinical characteristics of laryngocarcinoma patients were also recorded. After transfection, cell viability, cell proliferation, apoptosis, cell cycle, migration, and invasion were detected by cell counting kit-8 (CCK-8), colony formation, flow cytometry, cell scratch, and Transwell assays, respectively. Glycolysis was assessed by the colorimetric method. Expressions of proliferation-associated proteins, migration-associated proteins, glycolysis-associated proteins, and phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signal pathway-associated proteins were detected by Western blot. RESULTS: In laryngocarcinoma tumor tissues and cells, LINC00941 was highly expressed. High expression of LINC00941 decreased the 5-year survival of laryngocarcinoma patients, and it was positively related to lymph node metastasis and clinical stages. LINC00941 overexpression decreased apoptosis but promoted cell viability, proliferation, cell-cycle progression, migration, and invasion, and glucose consumption and lactate production in laryngocarcinoma cells. Moreover, LINC00941 overexpression elevated expressions of Ki-67, PCNA, MMP2, N-Cadherin, HK2, PFKFB4, and PKM, activated the PI3K/AKT/mTOR signal pathway but reduced E-Cadherin expression, while LINC00941 silencing had the opposite effects. PKM overexpression reversed the effects of LINC00941 silencing on cellular and glycolytic phenotypes. CONCLUSION: LINC00941 promoted in vitro progression and glycolysis of laryngocarcinoma cells by upregulating PKM via activating the PI3K/AKT/mTOR signaling pathway.


Assuntos
Fosfatidilinositol 3-Quinase , Fosfatidilinositol 3-Quinases , Apoptose/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Glicólise/genética , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinase/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
8.
Viral Immunol ; 35(2): 170-174, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35167777

RESUMO

Widespread vaccination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine makes the assessment of antibodies' positive rates essential. In this study, a total of 378 hospital staff members vaccinated with the vaccine were selected as research subjects. Serum-specific IgG and IgM against the SARS-CoV-2 spike protein (S) were detected, and S-specific IgG and IgM positive rates were analyzed in different age and sex groups, as was the serological pattern of IgG/IgM. The positive rates of IgG and IgM were 92.06% and 44.44%, respectively. The percentage of both IgG and IgM positive (IgG+IgM+) was 43.92%. A total of 182 vaccinees (46.90%) were IgG positive and IgM negative (IgG+IgM-), and 28 vaccinees (7.41%) were negative for both IgG and IgM (IgG-IgM-); 2 participants were positive for IgM alone (IgG-IgM+). In sex subgroups, the rate of IgM positivity was significantly higher in the male group than in the female group (p = 0.027). In different age subgroups, positive rates for IgG in the young group were significantly higher than those in the other group (p = 0.035). Furthermore, ratios of sample values to cutoff values (S/CO values) for IgG in vaccinees who were S-specific IgG positive were compared, and the S/CO values of IgG were significantly higher in the younger group than in the other group (p < 0.001). When comparing the influence of sex on two specific serological patterns (IgG+IgM- and IgG+IgM+), a significant difference in positivity rates was detected (p = 0.011). Male vaccinees were more likely than females to have an IgG+IgM+ pattern.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Anticorpos Antivirais , COVID-19/prevenção & controle , Feminino , Humanos , Imunoglobulina G , Imunoglobulina M , Masculino , Recursos Humanos em Hospital , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
9.
Ann Palliat Med ; 10(10): 10401-10413, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34763486

RESUMO

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease COPD (AECOPD) can cause a significant decrease in patient lung function, and are the main reason for hospitalization and death of patients with COPD. This study aims to use bibliometric methods to analyze the characteristics of AECOPD related research in the past 10 years [2010-2020] and provide references for future research. METHODS: This study used subject terms to search AECOPD-related documents published in 2010-2020 in the Science Citation Index Expanded (SCI-E) database. The search terms were "AECOPD" or "acute exacerbation of chronic obstructive pulmonary disease." We use the CiteSpace software to analyze the target literature records. The analysis includes: the annual distribution of literature publications, the distribution of published literature sources (including countries, institutions, journals, and authors), and using keywords. RESULTS: A total of 3,785 articles on AECOPD were published between 2010 and 2020, with 62,162 citations. Both the number of published documents and the number of citations has increased with time. The literature mainly comes from several developed countries, including European and North American countries, and the cooperation between institutions and authors in these countries is relatively close. The main journals are the top journals of respiratory specialty and the top comprehensive journals. The results of the keyword analysis show that the current research is on risk factors, biomarkers, and AECOPD management. CONCLUSIONS: AECOPD research tends to focus on a precise diagnosis and treatment, and prevention of AECOPD in patients with COPD should be paid more attention.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Bibliometria , Bases de Dados Factuais , Hospitalização , Humanos , Fatores de Risco
10.
Immunobiology ; 226(5): 152133, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34469785

RESUMO

BACKGROUND AND AIMS: Pyroptosis is a relatively newly discovered form of programmed cell death that plays an important role in the development of atherosclerosis. Many studies have reported that lncRNAs participated in the regulation of atherosclerosis development. However, the regulatory mechanism of lncRNAs in pyroptosis must be studied further. METHODS: In a previous study, microarray analysis was used to detect the lncRNA expression profile in three human advanced atherosclerotic plaques and three normal arterial intimae. In the present research, in vitro assays were performed to investigate the role of lncRNA RP11-490M8.1 on pyroptosis. The relative gene mRNA and lncRNA expression levels were tested by quantitative real-time PCR, and protein levels were evaluated by western blot analysis. The RNA hybrid structure was analyzed using the DINAMelt server. RESULTS: The lncRNA RP11-490M8.1 was significantly downregulated in atherosclerotic plaques and serum. Lipopolysaccharide (LPS) markedly reduced the expression of lncRNA RP11-490M8.1 and induced pyroptosis by increasingthe mRNA and protein levels of NLRP3, caspase-1, ASC, IL-1ß, and IL-18 in HUVECs. The promotion effects ofLPS on pyroptosis were markedly suppressed by overexpression of lncRNA RP11-490M8.1. In addition, LPS increased the mRNA and protein levels ofTLR4 and NF-κB, which was also markedly offsetby overexpression of lncRNA RP11-490M8.1. CONCLUSIONS: These findings indicated that lncRNA RP11-490M8.1 inhibited LPS-induced pyroptosis via the TLR4/NF-κB pathway. Thus, lncRNA RP11-490M8.1 may provide a therapeutic target to ameliorate atherosclerosis.


Assuntos
Células Endoteliais da Veia Umbilical Humana , NF-kappa B , Piroptose , RNA Longo não Codificante , Receptor 4 Toll-Like , Aterosclerose/genética , Proteínas Adaptadoras de Sinalização CARD/genética , Caspase 1/genética , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamassomos/genética , Inflamassomos/metabolismo , Interleucina-18/genética , Interleucina-1beta/genética , Lipopolissacarídeos/farmacologia , NF-kappa B/genética , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/efeitos dos fármacos , RNA Mensageiro , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
11.
Am J Transl Res ; 13(7): 8409-8414, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34377336

RESUMO

OBJECTIVE: To evaluate the application of sputum suction by fiberoptic bronchoscope to patients with severe pneumonia and its effect on inflammatory factors. METHODS: One hundred and three patients with severe pneumonia were randomly divided into the control group (n=52) and the observation group (n=51). Both groups were given anti-infection, antitussive and expectoration treatment. The observation group was treated with sputum suction by fiberoptic bronchoscope. The control group was treated with a vibration sputum extractor. The clinical efficacy, clinically related indexes, inflammatory factors, blood gas indexes and the Acute Physiology and Chronic Health Evaluation (APACHE II) score of the two groups were compared. RESULTS: After the treatment, the total effective rate of the observation group was higher than that of the control group; the length of stay in ICU, mechanical ventilation time and duration of antibiotics of the observation group were shorter than those of the control group (all P<0.05). After the treatment, the serum levels of CRP, TNF-α and PCT and APACHE II scores in the two groups were all decreased, while PaO2, SaO2 and OI were increased; the changes in the observation group were more significant than the control group (all P<0.05). CONCLUSION: Sputum suction and lavage by fiberoptic bronchoscope can significantly control the body's inflammatory reaction state in patients with severe pneumonia, improve their blood oxygen and promote the treatment effect.

12.
Nat Commun ; 12(1): 4538, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315863

RESUMO

How the human cytomegalovirus (HCMV) genome-the largest among human herpesviruses-is packaged, retained, and ejected remains unclear. We present the in situ structures of the symmetry-mismatched portal and the capsid vertex-specific components (CVSCs) of HCMV. The 5-fold symmetric 10-helix anchor-uncommon among known portals-contacts the portal-encircling DNA, which is presumed to squeeze the portal as the genome packaging proceeds. We surmise that the 10-helix anchor dampens this action to delay the portal reaching a "head-full" packaging state, thus facilitating the large genome to be packaged. The 6-fold symmetric turret, latched via a coiled coil to a helix from a major capsid protein, supports the portal to retain the packaged genome. CVSCs at the penton vertices-presumed to increase inner capsid pressure-display a low stoichiometry, which would aid genome retention. We also demonstrate that the portal and capsid undergo conformational changes to facilitate genome ejection after viral cell entry.


Assuntos
Citomegalovirus/química , Citomegalovirus/genética , Empacotamento do DNA/genética , Genoma Viral , Capsídeo/química , Capsídeo/ultraestrutura , Proteínas do Capsídeo/metabolismo , Linhagem Celular , Citomegalovirus/ultraestrutura , DNA Viral/genética , DNA Viral/ultraestrutura , Humanos , Modelos Moleculares , Homologia Estrutural de Proteína , Vírion/química , Vírion/ultraestrutura
13.
Phys Chem Chem Phys ; 23(15): 9539-9552, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33885060

RESUMO

In this paper, we demonstrate a combined theoretical and experimental study on the electronic structure, and the optical and electrochemical properties of ß-Ag2MoO4 and Ag2O. These crystals were synthesized using the hydrothermal method and were characterized using X-ray diffraction (XRD), Rietveld refinement, and TEM techniques. XRD and Rietveld results confirmed that ß-Ag2MoO4 has a spinel-type cubic structure. The optical properties were investigated by UV-Vis spectroscopy. DFT+U formalism, via on-site Coulomb corrections for the d orbital electrons of Ag and Mo atoms (Ud) and the 2p orbital electrons of O atoms (Up) provided an improved band gap for ß-Ag2MoO4. Examination of the density of states revealed the energy states in the valence and conduction bands of the ß-Ag2MoO4 and Ag2O. The theoretical band structure indicated an indirect band gap of approximately 3.41 eV. Furthermore, CO2 electroreduction, and hydrogen and oxygen evolution reactions on the surface of ß-Ag2MoO4 and Ag2O were studied and a comparative investigation on molybdate-derived silver and oxide-derived silver was performed. The electrochemical results demonstrate that ß-Ag2MoO4 and Ag2O can be good electrocatalysts for water splitting and CO2 reduction. The CO2 electroreduction results also indicate that CO2 reduction intermediates adsorbed strongly on the surface of Ag2O, which increased the overpotential for the hydrogen evolution reaction on the surface of Ag2O by as much as 0.68 V against the value of 0.6 V for Ag2MoO4, at a current density of -1.0 mA cm-2.

14.
Nat Struct Mol Biol ; 28(3): 319-325, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33674802

RESUMO

The COVID-19 pandemic caused by nonstop infections of SARS-CoV-2 has continued to ravage many countries worldwide. Here we report that suramin, a 100-year-old drug, is a potent inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and acts by blocking the binding of RNA to the enzyme. In biochemical assays, suramin and its derivatives are at least 20-fold more potent than remdesivir, the currently approved nucleotide drug for treatment of COVID-19. The 2.6 Å cryo-electron microscopy structure of the viral RdRp bound to suramin reveals two binding sites. One site directly blocks the binding of the RNA template strand and the other site clashes with the RNA primer strand near the RdRp catalytic site, thus inhibiting RdRp activity. Suramin blocks viral replication in Vero E6 cells, although the reasons underlying this effect are likely various. Our results provide a structural mechanism for a nonnucleotide inhibitor of the SARS-CoV-2 RdRp.


Assuntos
Antivirais/farmacologia , RNA-Polimerase RNA-Dependente de Coronavírus/antagonistas & inibidores , RNA-Polimerase RNA-Dependente de Coronavírus/química , Inibidores Enzimáticos/farmacologia , Suramina/farmacologia , Animais , Antivirais/química , Antivirais/metabolismo , Sítios de Ligação , Domínio Catalítico , Chlorocebus aethiops , RNA-Polimerase RNA-Dependente de Coronavírus/metabolismo , Microscopia Crioeletrônica , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Conformação Proteica , RNA Viral/química , RNA Viral/metabolismo , SARS-CoV-2/efeitos dos fármacos , Suramina/química , Suramina/metabolismo , Células Vero , Replicação Viral/efeitos dos fármacos
15.
ACS Sens ; 6(2): 493-501, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33369390

RESUMO

The effects of temperature and molecular concentration on the ordering of two-dimensional (2D) nanostructures have been investigated at the well-defined Au(111)-electrolyte interface. In comparison to the assembly of thiolated alkanes or hydrogen-bonded nonthiolated molecules, fabricating large aromatic thiolated molecules into a highly ordered adlayer on a surface remained a challenge. In this study, we demonstrated the importance of controlling the assembly conditions and procedures for the formation of ordered adlayers of redox-active viologen derivatives. The assembly conditions that were explored include the variation of molar concentration of assembly solutions, assembly time, and thermal annealing. We report that the optimal assembly conditions for creating highly ordered thiolated viologen derivatives on a Au(111)-(1 × 1) electrode surface are to limit the time in which the electrode is immersed in a deoxygenated 0.05 mM ethanolic viologen solution (preheated to 70 °C) to 45 s, followed by thermal annealing in absolute ethanol for 12 h. Highly ordered molecular adlayers were imaged by electrochemical scanning tunneling microscopy (STM), revealing the molecular packing of low-coverage adlayers. Furthermore, in situ STM combined with cyclic voltammetry (CV) allowed for the exploration of the structural transformation and potential limit of reductive and "oxidative" desorption of adlayers within the electrochemical potential range of the sample potential (ES) from -0.95 V to -0.10 V vs SCE.


Assuntos
Ouro , Viologênios , Eletrodos , Eletrólitos , Imagem Molecular
16.
Cancer Manag Res ; 12: 10789-10797, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33149684

RESUMO

BACKGROUND: It is controversial whether contralateral prophylactic central neck dissection (PCND) should be performed for patients with solitary and clinical lymph node negative (cN0) papillary thyroid carcinoma (PTC) although routine ipsilateral PCND is required. OBJECTIVE: The aim of this study was to develop an improved nomogram including clinical features, ultrasound, and acoustic radiation force impulse (ARFI) elastography for the prediction of contralateral central lymph node metastasis (CLNM) in patients with solitary and cN0 PTC in the preoperative period. MATERIALS AND METHODS: A total of 340 patients were retrospectively included as the training cohort and 170 patients as the external validation cohort. Patients were grouped according to the pathological results of contralateral CLNM. The association between the clinical characteristics, ultrasound, and ARFI elastography and the risk for contralateral CLNM were analyzed. A nomogram was established based on the result of multivariable logistic analysis to predict the risk of contralateral CLNM, which was assessed by internal and external validation. RESULTS: CLNM was found in 213 patients (41.8%), among whom 142 (27.8%) had ipsilateral CLNM and 95 (18.6%) had contralateral CLNM (including 68 (13.3%) with bilateral CLNM). Multivariable analysis revealed that patients with younger age, male gender, larger tumor size, closer distance from the capsule, microcalcification, and larger SWVmean were independent predictors associated with the contralateral CLNM (P < 0.05), which was served as the basis of the nomogram. It showed good discrimination (C-index: 0.856) and calibration (χ2 = 9.028, P = 0.340, Hosmer-Lemeshow test) in the training cohort, and good discrimination was maintained in the external validation cohort (C-index: 0.792). CONCLUSION: The nomogram utilizing the features of ultrasound combined with ARFI elastography in preoperatively predicting the risk of contralateral CLNM in patients with solitary and cN0 PTC was established, which showed superior performance both in internal and external validation.

17.
Cell Res ; 30(10): 873-884, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32620850

RESUMO

Epstein-Barr virus (EBV) is the primary cause of infectious mononucleosis and has been shown to be closely associated with various malignancies. Here, we present a complete atomic model of EBV, including the icosahedral capsid, the dodecameric portal and the capsid-associated tegument complex (CATC). Our in situ portal from the tegumented capsid adopts a closed conformation with its channel valve holding the terminal viral DNA and with its crown region firmly engaged by three layers of ring-like dsDNA, which, together with the penton flexibility, effectively alleviates the capsid inner pressure placed on the portal cap. In contrast, the CATCs, through binding to the flexible penton vertices in a stoichiometric manner, accurately increase the inner capsid pressure to facilitate the pressure-driven genome delivery. Together, our results provide important insights into the mechanism by which the EBV capsid, portal, packaged genome and the CATCs coordinately achieve a pressure balance to simultaneously benefit both viral genome retention and ejection.


Assuntos
Capsídeo/ultraestrutura , Herpesvirus Humano 4/ultraestrutura , Substâncias Macromoleculares/química , Modelos Moleculares , Capsídeo/química , Proteínas do Capsídeo/química , Microscopia Crioeletrônica , DNA Viral/química , Herpesvirus Humano 4/química
19.
Cell Res ; 29(12): 971-983, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31776446

RESUMO

Arrestins comprise a family of signal regulators of G-protein-coupled receptors (GPCRs), which include arrestins 1 to 4. While arrestins 1 and 4 are visual arrestins dedicated to rhodopsin, arrestins 2 and 3 (Arr2 and Arr3) are ß-arrestins known to regulate many nonvisual GPCRs. The dynamic and promiscuous coupling of Arr2 to nonvisual GPCRs has posed technical challenges to tackle the basis of arrestin binding to GPCRs. Here we report the structure of Arr2 in complex with neurotensin receptor 1 (NTSR1), which reveals an overall assembly that is strikingly different from the visual arrestin-rhodopsin complex by a 90° rotation of Arr2 relative to the receptor. In this new configuration, intracellular loop 3 (ICL3) and transmembrane helix 6 (TM6) of the receptor are oriented toward the N-terminal domain of the arrestin, making it possible for GPCRs that lack the C-terminal tail to couple Arr2 through their ICL3. Molecular dynamics simulation and crosslinking data further support the assembly of the Arr2‒NTSR1 complex. Sequence analysis and homology modeling suggest that the Arr2‒NTSR1 complex structure may provide an alternative template for modeling arrestin-GPCR interactions.


Assuntos
Receptores de Neurotensina , beta-Arrestina 2 , Humanos , Simulação de Acoplamento Molecular/métodos , Ligação Proteica , Conformação Proteica , Receptores de Neurotensina/química , Receptores de Neurotensina/metabolismo , beta-Arrestina 2/química , beta-Arrestina 2/metabolismo
20.
Langmuir ; 35(41): 13259-13267, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31580684

RESUMO

Self-assembly provides unique routes to create supramolecular nanostructures at well-defined surfaces. In the present work, we employed scanning tunneling microscopy (STM) in combination with electrochemical techniques to explore the adsorption and phase formation of a series of aromatic carboxylic acids (ACAs) at Au(111)/0.1 M HClO4. Specific goals are to elucidate the roles of electrochemical potential and directional hydrogen-bonding on the structures and orientation of individual ACAs that form nanoarchitectures. ACAs are prototype materials for supramolecular self-assemblies via stereospecific hydrogen bonds between neighboring molecules. In this study, we mainly focus on a special ACA, terephthalic acid (TPA), which is almost insoluble in water, making the assembly of this molecule from aqueous solution challenging. Depending on the applied electric field, TPA molecules form distinctly different, highly ordered adlayers on Au(111) triggered by directional intermolecular hydrogen bonds. At low electrochemical potentials, TPA molecules are planar oriented, forming a potentially infinite hydrogen-bonded adlayer without any observed domain boundaries. The increase of the electrode potential triggers the deprotonation of one carboxylic acid functional group of TPA; additionally, this is accompanied by an orientation change of molecules from planar to perpendicular. In contrast, structural "defects" and multiple domain boundaries were found at this positively charged surface. The assembled nanostructures of TPA are compared with other ACAs (trimesic acid, benzoic acid, and isophthalic acid), and corresponding adsorption models were built for all molecular adlayers, showing that intermolecular hydrogen-bonding plays a determining role in the formation of two-dimensional ACA nanostructures.

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