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1.
J Am Chem Soc ; 143(49): 20779-20791, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34865478

RESUMO

The mitochondrial DNA G-quadruplex (mtDNA G4) is a potential regulatory element for the regulation of mitochondrial functions; however, its relevance and specific roles in diseases remain largely unknown. Here, we engineered a set of chemical probes, including MitoISCH, an mtDNA G4-specific fluorescent probe, together with MitoPDS, a mitochondria-targeted G4-stabilizing agent, to thoroughly investigate mtDNA G4s. Using MitoISCH to monitor previously intractable dynamics of mtDNA G4s, we surprisingly found that their formation was prevalent only in endothelial and cancer cells that rely on glycolysis for energy production. Consistent with this, promotion of mtDNA G4 folding by MitoPDS in turn caused glycolysis-related gene activation and glycolysis enhancement. Remarkably, this close relationship among mtDNA G4s, glycolysis, and cancer cells further allowed MitoISCH to accumulate in tumors and label them in vivo. Our work reveals an unprecedented link between mtDNA G4s and cell glycolysis, suggesting that mtDNA G4s may be a novel cancer biomarker and therapeutic target deserving further exploration.


Assuntos
DNA Mitocondrial/metabolismo , Corantes Fluorescentes/química , Quadruplex G , Glicólise/fisiologia , Células 3T3 , Animais , Linhagem Celular Tumoral , DNA Mitocondrial/genética , Células Endoteliais/metabolismo , Humanos , Camundongos , Camundongos Nus , Mitocôndrias/metabolismo
2.
J Econ Entomol ; 114(3): 1053-1064, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-33769525

RESUMO

Large-scale use of systemic pesticides has been considered a potential factor for pollinator population decline. Phytochemicals, e.g., quercetin, have been demonstrated to increase the pesticide tolerance of Apis mellifera Linnaeus (Hymenoptera: Apidae), which is helpful to develop strategies to reduce the pesticides hazards to pollinators. In this study, we hypothesized phytochemicals could reduce the detrimental effects of imidacloprid on Apis cerana Fabricius. The lethal and sublethal effects of imidacloprid on A. cerana workers were investigated. The results showed that A. cerana workers chronically exposed to 100 µg/liter imidacloprid had a significantly shorter longevity by 10.81 d compared with control. Acute exposure to imidacloprid at 100 µg/liter impaired the sucrose responsiveness and memory retention of the workers, and 20 µg/liter reduced the sucrose responsiveness. The treatment with 37.8 mg/liter quercetin for 24 h could increase the longevity of A. cerana workers when chronically exposed to 100 µg/liter imidacloprid, and 75.6 mg/liter quercetin feeding treatment alleviated the impairment of sucrose responsiveness. However, workers treated with 151.2 mg/liter and 75.6 mg/liter quercetin had a significantly shorter longevity compared to that of bees chronically exposed to 100 µg/liter imidacloprid without quercetin treatment. Our results suggested that quercetin treatment could produce a biphasic influence on the lethal effects of imidacloprid on A. cerana. Quercetin at 37.8 mg/liter and 75.6 mg/liter in the diet before pesticide exposure was able to reduce the lethal and sublethal effects of imidacloprid, respectively, providing potential strategies to reduce the pesticides hazards to native honey bees (A. cerana).


Assuntos
Himenópteros , Inseticidas , Animais , Abelhas , Inseticidas/toxicidade , Neonicotinoides/toxicidade , Nitrocompostos/toxicidade , Quercetina
3.
Inorg Chem ; 59(17): 12941-12946, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32820911

RESUMO

Electrocatalytic nitrogen reduction reaction (NRR) is a green and sustainable strategy for artificial nitrogen fixation but remains a significant challenge because of the lack of high-performance electrocatalysts. In this study, flower-like hollow MoSe2 nanospheres as efficient earth-abundant NRR electrocatalysts with a high faradaic efficiency of 14.2% and an ammonia yield of 11.2 µg h-1 mgcat.-1 at ambient conditions were prepared. Such excellent NRR activity can be attributed to the higher specific surface area, more active sites, and longer N2 retention time within the shells because of the design of the hollow structure. Density functional theory calculations were performed to further understand the catalytic mechanism involved. This work demonstrates the feasibility of transition-metal selenides as NRR electrocatalysts and suggests an electrocatalyst materials structure design for efficient electrochemical nitrogen fixation.

4.
ACS Appl Mater Interfaces ; 12(34): 38106-38112, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32799447

RESUMO

Platinum-based single-atom catalysts (SACs) are among the most promising candidates for the practical applications of electrochemical hydrogen evolution reaction (HER), but their catalytic efficiency remains to be further enhanced. Herein, a well-designed nanoarray-structured nitrogen-doped graphite foil (NNGF) substrate is introduced to support Pt SACs in Pt-N4 construction (Pt1/NNGF) for HER. Within NNGF, the constructed nanoarray-structured surficial layer for supporting Pt SACs could enhance the exposure of active sites to the electrolyte and improve the reaction and diffusion kinetics; meanwhile, the retained graphite structures in bulk NNGF provide not only the required electrical conductivity but also the mechanical stability and flexibility. Because of such double-layer structures of NNGF, stable Pt-N4 construction, and binder-free advantages, the Pt1/NNGF electrode exhibits a low overpotential of 0.023 V at 10 mA cm-2 and a small Tafel slope of 29.1 mV dec-1 as well as an excellent long-term durability.

5.
Clin Infect Dis ; 71(9): 2421-2427, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31734699

RESUMO

BACKGROUND: Evaluation of a licensed inactivated enterovirus type 71 (EV71) vaccine is needed in a phase IV study with a large population to identify its effectiveness and safety for further application. METHODS: An open-label, controlled trial involving a large population of 155 995 children aged 6-71 months was performed; 40 724 were enrolled in the vaccine group and received 2 doses of inactivated EV71 vaccine at an interval of 1 month, and the remaining children were used as the control group. The EV71-infected cases with hand, foot, and mouth disease were monitored in the vaccine and control groups during a follow-up period of 14 months since the 28th day postinoculation through the local database of the Notifiable Infectious Diseases Network. The effectiveness of the vaccine was estimated by comparing the incidence density in the vaccine group versus that in the control group based upon EV71-infected patients identified via laboratory testing. In parallel, the active and passive surveillance for safety of the vaccine was conducted by home or telephone visits and by using the Adverse Event Following Immunization (AEFI) system, respectively. RESULTS: An overall level of 89.7% (95% confidence interval, 24.0-98.6%) vaccine effectiveness against EV71 infection and a 4.58% rate of reported adverse events were observed. Passive surveillance demonstrated a 0.31% rate of reported common minor reactions. CONCLUSIONS: The clinical protection and safety of the EV71 vaccine were demonstrated in the immunization of a large population. CLINICAL TRIALS REGISTRATION: NCT03001986.


Assuntos
Enterovirus Humano A , Enterovirus , Doença de Mão, Pé e Boca , Vacinas Virais , Adolescente , Adulto , Idoso , Anticorpos Antivirais , Criança , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/prevenção & controle , Humanos , Pessoa de Meia-Idade , Vacinas de Produtos Inativados/efeitos adversos , Adulto Jovem
6.
RSC Adv ; 10(33): 19576-19586, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35515446

RESUMO

The density functional theory (DFT) and DFT plus correction for on-site Coulomb interaction (DFT+U) method were performed to investigate the adsorption and dissociation of H2 on PuH2 (100), (110) and (111) surfaces. Overall, the H2 molecule can be adsorbed on the PuH2 surface without spontaneous dissociation. The calculated H-H bond lengths (R H-H) are all elongated to different degrees, and the R H-H at different adsorption sites is about 0.84-4.21% longer than in the gas phase. We found that the dissociation of H2 on the (110) surface is a spontaneous exothermic process, and a total energy of 0.60 eV is released in the whole process. The smaller barriers corroborate that the migration of an H atom on the PuH2 surface is possible, and even spontaneous diffusion may occur. The spontaneous migration of a hydrogen atom adsorbed on the (110) surface from the surface to the interior promotes the conversion of PuH2 to PuH3, which may be the fundamental driving force of hydrogenation corrosion. Our results provide useful information to explain the mechanism of hydrogenation corrosion on the PuH2 surface.

7.
ChemistryOpen ; 8(7): 1027-1032, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31367510

RESUMO

Developing cost-effective and highly efficient oxygen evolution reaction (OER) electrocatalysts is vital for the production of clean hydrogen by electrocatalytic water splitting. Here, three dimensional nickel-iron layered double hydroxide (NiFe LDH) nanosheet arrays are in-situ fabricated on self-supporting nitrogen doped graphited foam (NGF) via a one-step hydrothermal process under an optimized amount of urea. The as prepared NiFe LDH/NGF electrode exhibits a remarkable activity toward OER with a low onset overpotential of 233 mV and a Tafel slope of 59.4 mV dec-1 as well as a long-term durability. Such good performance is attributed to the synergy among the doping effect, the binder-free characteristic, and the architecture of the nanosheet array.

8.
Anal Chem ; 91(3): 2480-2487, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30618242

RESUMO

The specific sensing of an exact G-quadruplex structure by small molecules has never been reported. A fluorescent sensor based on the photoinduced electron transfer (PeT) mechanism provides possibilities for such specific, one-to-one recognition, indicated by fluorescence. We have rationally developed a PeT fluorescent sensor IZFL-2 by linking triarylimidazole and fluorescein moieties. IZFL-2 is a distinctive, smart sensor whose fluorescence is tunable by its molecular conformations. We then applied IZFL-2 to sensing G-quadruplexes and found that it could exactly distinguish the wild-type c-MYC G-quadruplex from other types of G-quadruplexes, as shown by the activation of its fluorescence. To understand this behavior, we performed various experiments, including fluorescence assays, absorption assays, and multiscale molecular dynamics simulations, to thoroughly investigate the optimal binding mode of IZFL-2 in the c-MYC G-quadruplex. Then, the corresponding HOMO-LUMO of IZFL-2 was analyzed, and the results demonstrated that the PeT process of IZFL-2 is suppressed only in the wild-type c-MYC G-quadruplex via specific loop interactions, which restores its fluorescence. To our knowledge, this smart molecule provides the first example of and new insights into the development of sensors specific for a particular G-quadruplex structure by utilizing intramolecular PeT-controlled fluorescence switching.


Assuntos
Corantes Fluorescentes/química , Quadruplex G , Proteínas Proto-Oncogênicas c-myc/genética , Sequência de Bases , Transporte de Elétrons , Simulação de Dinâmica Molecular , Mutação
9.
Mitochondrial DNA B Resour ; 4(2): 4071-4072, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33366323

RESUMO

We sequenced the complete chloroplast of Firmiana danxiaensis (Malvaceae), which is 161,253 bp in size and consists of a large single-copy region (LSC) of 90,142 bp and a short single copy region (SSC) of 20,067 bp. It was separated by two inverted repeats (IRs) regions of 25,522 bp for each. The GC content of the whole genome, LSC, SSC, and IRs region was 36.87%, 34.68%, 31.24%, and 42.97%, respectively. The overall base content was A (31.07%), T (32.05%), C (18.80%), and G (18.08%). The genome contained 127 genes, including 82 protein-coding sequences, 37 tRNA genes, and 8 rRNA genes. Phylogenetic analysis showed that F. danxiaensis is sister to F. simplex, and supported there was a close relationship among F. danxiaensis, F. simplex, and F. pulcherrima.

10.
J Am Chem Soc ; 140(51): 17945-17955, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30517002

RESUMO

The arginine/glycine-rich region termed the RGG domain is usually found in G-quadruplex (G4)-binding proteins and is important in G4-protein interactions. Studies on the binding mechanism of RGG domains found that small segments (RGG motif) inside the domain contribute greatly to the G4 binding affinity. However, unlike the entire RGG domains that have been broadly explored, the role of the RGG motif remains obscure, with very limited study. Herein, to clarify the role of the RGG motif in G4-protein interactions, we systematically investigated the binding affinity and mode between RGG-motif peptides and G4s. The internal arrangement of RGG repeats and gap amino acids played a more crucial role in the G4-binding mechanism than a critical number of RGG repeats. Arginines and phenylalanines at the exact position of the RGG motif might enable additional hydrogen bonding and π-stacking interaction with nucleobases and strengthen the binding of G4. Impressively, proceeding from a G4-binding RGG peptide, 12, discovered above, we identified the cold-inducible RNA-binding protein (CIRBP) as a new G4 DNA-binding protein both in vitro and in cells. In addition, we found that the key amino acids for G4 binding in peptide 12 and CIRBP were highly similar, and peptide 12 clearly played a key role in the G4 binding of CIRBP. This report is the first in which a G4-binding protein was identified from exploration of the G4-binding RGG motif. Our findings suggest a novel strategy for discovering new G4-binding proteins by exploring key peptide segments.


Assuntos
Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Proteínas de Ligação a RNA/metabolismo , Sequência de Aminoácidos , DNA/genética , Quadruplex G , Células HeLa , Humanos , Mutação , Peptídeos/genética , Peptídeos/metabolismo , Ligação Proteica
11.
Rev Sci Instrum ; 89(8): 083103, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30184661

RESUMO

Raman imaging has a great advantage in characterizing inhomogeneous systems. A practical wide-field Raman imaging platform is developed that shows major improvements on imaging speed, sensitivity, and resolution. Different from the traditional Raman imaging systems using the wavelength-fixed lasers and the chromatic dispersion devices, this system adopts an inverted architecture, integrated with a tunable laser and the wavelength-fixed filters. Owing to the high transmission of the fixed filters, the imaging sensitivity can be improved 5-10 times in comparison to the present wide-field Raman imaging setups using liquid-crystal tunable filters. Via combining with the high-power tunable laser, Raman images could be obtained in minutes and the Raman shift of the images could be tuned easily and accurately. The resolution of this system can reach 1.5 cm-1 in the spectrum and 490 nm in space, which could provide more fingerprint details of the analytes. This effective Raman imaging method allowing us to see chemical spatial variations on microscale is anticipated to be widely applied in scientific research fields.

12.
Zhongguo Yi Liao Qi Xie Za Zhi ; 42(1): 58-61, 2018 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-29862750

RESUMO

OBJECTIVES: To solve the problem that medical device adverse event monitoring entities perform their duties inadequately, to provide reference for perfecting the post-market surveillance system. METHODS: Through theoretical and empirical research, the paper explored the ways to improve the performance of monitoring the adverse events of medical devices. RESULTS: The survey found that the number of adverse event monitoring reports was few and the quality of report was poor. The root causes included lack of motivation of monitoring entities, the imperfect monitoring system, and the monitoring capability failure, etc. CONCLUSIONS: The methods such as strengthening the main body responsibility consciousness, establishing evaluation system and accountability system, building social work network, are beneficial to the adverse events monitoring.


Assuntos
Equipamentos e Provisões/efeitos adversos , Vigilância de Produtos Comercializados , Segurança de Equipamentos , Inquéritos e Questionários
13.
Scanning ; 2018: 5736742, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29721128

RESUMO

The effects of ball milling on the hydrogen sorption kinetics and microstructure of Zr0.8Ti0.2Co have been systematically studied. Kinetic measurements show that the hydrogenation rate and amount of Zr0.8Ti0.2Co decrease with increasing the ball milling time. However, the dehydrogenation rate accelerates as the ball milling time increases. Meanwhile, the disproportionation of Zr0.8Ti0.2Co speeds up after ball milling and the disproportionation kinetics is clearly inclined to be linear with time at 500°C. It is found from X-ray powder diffraction (XRD) results that the lattice parameter of Zr0.8Ti0.2Co gradually decreases from 3.164 Å to 3.153 Å when the ball milling time extends from 0 h to 8 h, which is mainly responsible for the hydrogen absorption/desorption behaviors. In addition, scanning electron microscope (SEM) images demonstrate that the morphology of Zr0.8Ti0.2Co has obviously changed after ball milling, which is closely related to the hydrogen absorption kinetics. Besides, high-resolution transmission electron microscopy (HRTEM) images show that a large number of disordered microstructures including amorphous regions and defects exist after ball milling, which also play an important role in hydrogen sorption performances. This work will provide some insights into the principles of how to further improve the hydrogen sorption kinetics and disproportionation property of Zr0.8Ti0.2Co.

14.
Ther Innov Regul Sci ; 50(1): 74-81, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30236012

RESUMO

BACKGROUND: The 12th Five-Year Plan period is a critical period for the development of the pharmaceutical industry in China. A major focus coming with the New Healthcare Reform is a product structure adjustment in the pharmaceutical industry. Many researchers have been attracted in recent years to product structure adjustment studies. METHODS: An empirical analysis of resources of the New Healthcare Reform was conducted by employing clustering analysis. A panel data model was established, with independent variables consisting of the city residents' medical insurance fund, drug fees per capita, city medical insurance fees per capita, rural medical insurance fees per capita, and number of people benefiting from the new rural cooperative medical scheme and the dependent variable being China's medical technology advancement fees. This study covered 29 provinces and regions and used panel data from 2007 to June 2012 to establish a fundamental regression equation for quantitative analysis. RESULTS: The city residents' medical insurance fund, rural medical insurance fees, and the new rural cooperative medical scheme are significant factors for pharmaceutical structure adjustment in China. The rural medical services market is the most important target market for pharmaceutical industrial transformation. CONCLUSION: The fundamental drug system and medical insurance system, which the New Healthcare Reform focuses upon, are closely related to the pharmaceutical product structure. For entities in which structural adjustment is not autonomous, changes can be achieved through sound coordination between organizational structure, technical structure, and repeated evaluation of consistency of drug product quality and overseas technical license.

15.
J Invertebr Pathol ; 127: 110-4, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25805518

RESUMO

Previous surveys have shown that adult workers of the Asian honey bee Apis cerana harbor four major gut microbes (Bifidobacterium, Snodgrassella alvi, Gilliamella apicola, and Lactobacillus). Using quantitative PCR we characterized gut bacterial communities across the life cycle of A. cerana from larvae to workers. Our results indicate that the presence and quantity of these four bacteria were low on day 1, increased rapidly after day 5, and then peaked during days 10-20. They stabilized from days 20-25 or days 25-30, then dropped to a low level at day 30. In addition, the larvae infected by Sacbrood virus or European foulbrood had significantly lower copies of 16S rRNA genes than healthy individuals.


Assuntos
Abelhas/microbiologia , Microbioma Gastrointestinal , Animais , Abelhas/crescimento & desenvolvimento , Reação em Cadeia da Polimerase
16.
Onco Targets Ther ; 8: 147-55, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25609982

RESUMO

BACKGROUND: Single-nucleotide polymorphisms in apoptosis-related genes have been shown to play a role in the efficacy of platinum-based chemotherapy and may influence clinical outcomes. Our study aimed to evaluate the correlations of four functional single-nucleotide polymorphisms - FAS -670 A>G, FAS ligand -844 T>C, survivin -31 G>C, and survivin 9386 C>T - with drug response and clinical outcomes in advanced non-small-cell lung cancer patients who received platinum-based chemotherapy. MATERIALS AND METHODS: Polymorphisms were evaluated using the polymerase chain reaction-based restriction fragment-length polymorphism technique. RESULTS: Patients with the CC genotype of FAS -670 A>G had worse overall survival (OS) than those with the CT or TT genotype (P=0.044), with median OS values of 20.1 months, 22.8 months, and 26.0 months, respectively. Furthermore, progression-free survival was associated with the FAS -670 A>G polymorphism (P=0.032). In addition, patients with the TC and CC genotypes of survivin 9386 C>T experienced improved survival compared with patients with the TT genotype (median OS 31.4 months and 22.8 months, respectively). CONCLUSION: The functional FAS -670 A>G and survivin 9386 C>T polymorphisms are potential independent prognostic factors in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy.

17.
PLoS One ; 9(9): e106162, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25181318

RESUMO

OBJECTIVE: The aim of this paper was to compare the efficacy and safety of S-1-based and capecitabine-based preoperative chemoradiotherapy regimens in patients with locally advanced rectal cancer through a retrospective matched-pair analysis. MATERIALS AND METHODS: Between Jan 2010 and Mar 2014, 24 patients with locally advanced rectal cancer who received preoperative radiotherapy concurrently with S-1 were individually matched with 24 contemporary patients with locally advanced rectal cancer who received preoperative radiotherapy concurrently with capecitabine according to clinical stage (as determined by pelvic magnetic resonance imaging and computed tomography) and age (within five years). All these patients performed mesorectal excision 4-8 weeks after the completion of chemoradiotherapy. RESULTS: The tumor volume reduction rates were 55.9±15.1% in the S-1 group and 53.8±16.0% in the capecitabine group (p = 0.619). The overall downstaging, including both T downstaging and N downstaging, occurred in 83.3% of the S-1 group and 70.8% of the capecitabine group (p = 0.508). The significant tumor regression, including regression grade I and II, occurred in 33.3% of S-1 patients and 25.0% of capecitabine patients (p = 0.754). In the two groups, Grade 4 adverse events were not observed and Grade 3 consisted of only two cases of diarrhea, and no patient suffered hematologic adverse event of Grade 2 or higher. However, the incidence of diarrhea (62.5% vs 33.3%, p = 0.014) and hand-foot syndrome (29.2% vs 0%, p = 0.016) were higher in capecitabine group. Other adverse events did not differ significantly between two groups. CONCLUSIONS: The two preoperative chemoradiotherapy regimens were effective and safe for patients of locally advanced rectal cancer, but regimen with S-1 exhibited a lower incidence of adverse events.


Assuntos
Quimiorradioterapia , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Ácido Oxônico/uso terapêutico , Cuidados Pré-Operatórios , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Tegafur/uso terapêutico , Capecitabina , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ácido Oxônico/efeitos adversos , Cuidados Pós-Operatórios , Tegafur/efeitos adversos , Resultado do Tratamento
18.
Oncol Lett ; 7(5): 1605-1607, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24765186

RESUMO

Primary anorectal (PA) malignant melanoma (MM) is a rare disease associated with a high mortality rate. The most appropriate treatment strategy for PAMM remains controversial. A 55-year-old female patient, who was misdiagnosed with locally advanced rectal carcinoma, was treated with preoperative radiotherapy and concurrent oral capecitabine. During the therapy, grade 1 leukopenia occurred, however, there was no interruption to treatment. Following chemoradiotherapy, a computer tomography scan identified that the tumor had shrunk significantly and the original enlarged lymph nodes had disappeared. Eight weeks after completion of chemoradiotherapy, sphincter-sparing surgery was performed on the patient and based on the postoperative pathological result, MM was diagnosed. At the time of writing, the patient has survived disease-free for 15 months and at the most recent follow-up examination the Karnofsky Performance Scale score was 100. The therapeutic regimen of neoadjuvant concurrent chemoradiotherapy together with sphincter-sparing surgery is considered to be an optimal choice for patients with PAMM. However, further studies are required to evaluate the efficacy and clinical utility of this therapeutic regimen.

19.
J Biol Chem ; 289(16): 11020-11028, 2014 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-24619408

RESUMO

The catalytic domain of XynCDBFV, a glycoside hydrolase family 11 (GH11) xylanase from ruminal fungus Neocallimastix patriciarum previously engineered to exhibit higher specific activity and broader pH adaptability, holds great potential in commercial applications. Here, the crystal structures of XynCDBFV and its complex with substrate were determined to 1.27-1.43 Å resolution. These structures revealed a typical GH11 ß-jelly-roll fold and detailed interaction networks between the enzyme and ligands. Notably, an extended N-terminal region (NTR) consisting of 11 amino acids was identified in the XynCDBFV structure, which is found unique among GH11 xylanases. The NTR is attached to the catalytic core by hydrogen bonds and stacking forces along with a disulfide bond between Cys-4 and Cys-172. Interestingly, the NTR deletion mutant retained 61.5% and 19.5% enzymatic activity at 55 °C and 75 °C, respectively, compared with the wild-type enzyme, whereas the C4A/C172A mutant showed 86.8% and 23.3% activity. These results suggest that NTR plays a role in XynCDBFV thermostability, and the Cys-4/Cys-172 disulfide bond is critical to the NTR-mediated interactions. Furthermore, we also demonstrated that Pichia pastoris produces XynCDBFV with higher catalytic activity at higher temperature than Escherichia coli, in which incorrect NTR folding and inefficient disulfide bond formation might have occurred. In conclusion, these structural and functional analyses of the industrially favored XynCDBFV provide a molecular basis of NTR contribution to its thermostability.


Assuntos
Proteínas Fúngicas/química , Neocallimastix/enzimologia , Xilosidases/química , Cristalografia por Raios X , Proteínas Fúngicas/genética , Ligação de Hidrogênio , Neocallimastix/genética , Estrutura Terciária de Proteína , Relação Estrutura-Atividade , Xilosidases/genética
20.
PLoS One ; 8(12): e82211, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24358156

RESUMO

OBJECTIVE: This study aimed to construct a model for using in differentiating benign and malignant nodules with the artificial neural network and to increase the objective diagnostic accuracy of US. MATERIALS AND METHODS: 618 consecutive patients (528 women, 161 men) with 689 thyroid nodules (425 malignant and 264 benign nodules) were enrolled in the present study. The presence and absence of each sonographic feature was assessed for each nodule - shape, margin, echogenicity, internal composition, presence of calcifications, peripheral halo and vascularity on color Doppler. The variables meet the following criteria: important sonographic features and statistically significant difference were selected as the input layer to build the ANN for predicting the malignancy of nodules. RESULTS: Six sonographic features including shape (Taller than wide, p<0.001), margin (Not Well-circumscribed, p<0.001), echogenicity (Hypoechogenicity, p<0.001), internal composition (Solid, p<0.001), presence of calcifications (Microcalcification, p<0.001) and peripheral halo (Absent, p<0.001) were significantly associated with malignant nodules. A three-layer 6-8-1 feed-forward ANN model was built. In the training cohort, the accuracy of the ANN in predicting malignancy of thyroid nodules was 82.3% (AURO  = 0.818), the sensitivity and specificity was 84.5% and 79.1%, respectively. In the validation cohort, the accuracy, sensitivity and specificity was 83.1%, 83.8% and 81.8%, respectively. The AUROC was 0.828. CONCLUSION: ANN constructed by sonographic features can discriminate benign and malignant thyroid nodules with high diagnostic accuracy.


Assuntos
Redes Neurais de Computação , Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Ultrassonografia
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