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1.
Hepatology ; 76(1): 66-77, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35007334

RESUMO

BACKGROUND AND AIMS: The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3-5-cm HCC over time. APPROACH AND RESULTS: From 2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008-2019 (n = 335 in each group) and 2014-2019 (n = 257 in each group) cohorts, respectively. For cohort 2008-2019, during a median follow-up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65-1.19, p = 0.420), and MWA was inferior to LLR regarding disease-free survival (DFS) (HR 1.36, 95% CI 1.05-1.75, p = 0.017). For cohort 2014-2019, there was comparable OS (HR 0.85, 95% CI 0.56-1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98-1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1-4.0-cm HCCs (HR 0.88, 95% CI 0.53-1.47, p = 0.630) and 4.1-5.0-cm HCCs (HR 0.77, 95% CI 0.37-1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001). CONCLUSIONS: MWA might be a first-line alternative to LLR for solitary 3-5-cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Laparoscopia , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Hepatectomia , Humanos , Neoplasias Hepáticas/patologia , Micro-Ondas/uso terapêutico , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
2.
Anesth Analg ; 134(3): 615-623, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34878412

RESUMO

BACKGROUND: Hypoxemia can occur during gastroscopy under intravenous anesthesia. The aim of this randomized controlled trial was to evaluate whether oxygenation using a nasal mask can reduce the incidence of hypoxemia during gastroscopy under intravenous anesthesia compared with a traditional nasal cannula. METHODS: A total of 574 patients scheduled for gastroscopy under intravenous anesthesia were enrolled and randomly assigned to receive either a nasal mask or a traditional nasal cannula for oxygenation. The primary outcome was the incidence of hypoxemia. The secondary outcomes included the incidence of severe hypoxemia, duration of hypoxemia, minimum oxygen saturation, the proportion of emergency airway management, length of procedure, recovery time, and the satisfaction of the anesthetist and gastroenterologists as well as other adverse events (including cough, hiccups, nausea and vomiting, reflux, aspiration, and laryngospasm). RESULTS: A total of 565 patients were included in the analysis: 282 patients in the nasal cannula group and 283 patients in the nasal mask group. The incidence of hypoxemia was lower in the nasal mask group (18.0%) than in the nasal cannula group (27.7%; relative risk [RR] = 0.65; 95% confidence interval [CI], 0.48-0.89; P = .006), and the hypoxemia lasted a median of 18.0 seconds (interquartile range, 10.0-38.8) in the nasal mask group and 32.5 seconds (20.0-53.5) in the nasal cannula group (median difference -14.50; 95% CI, -22.82 to -1.34; P = .047). The proportion of patients requiring emergency airway management was significantly lower in the nasal mask group (8.8%) than in the nasal cannula group (19.1%; RR, 0.46; 95% CI, 0.30-0.73; P < .001). No difference was found in the overall incidence of other adverse events between the 2 groups (nasal mask 20.8%; nasal cannula 17.0%; RR, 1.23; 95% CI, 0.87-1.73; P = .25). Satisfaction was higher with the nasal mask than with the nasal cannula from the perspective of anesthetists (96.1% for nasal mask versus 84.4% for nasal cannula; RR, 1.14; 95% CI, 1.08-1.20; P < .001) and gastroenterologists (95.4% for mask versus 81.9% for cannula; RR, 1.17; 95% CI, 1.10-1.24; P < .001). There were no significant differences in the incidence of severe hypoxemia, minimum oxygen saturation, length of procedure, or recovery time between the 2 groups. CONCLUSIONS: Nasal mask oxygenation reduced the incidence of hypoxemia during anesthesia for gastroscopy under intravenous anesthesia.


Assuntos
Manuseio das Vias Aéreas/métodos , Anestesia Intravenosa/métodos , Gastroscopia/métodos , Hipóxia/epidemiologia , Máscaras , Nariz , Complicações Pós-Operatórias/epidemiologia , Adulto , Período de Recuperação da Anestesia , Anestesiologistas , Cateterismo , Feminino , Gastroenterologistas , Humanos , Hipóxia/etiologia , Incidência , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Oxigênio/sangue , Resultado do Tratamento
3.
Proc Natl Acad Sci U S A ; 115(51): E11933-E11942, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30463954

RESUMO

In kinesin-3, the coiled-coil 1 (CC1) can sequester the preceding neck coil (NC) for autoinhibition, but the underlying mechanism is poorly understood. Here, we determined the structures of the uninhibited motor domain (MD)-NC dimer and inhibited MD-NC-CC1 monomer of kinesin-3 KIF13B. In the MD-NC-CC1 monomer, CC1 is broken into two short helices that unexpectedly interact with both the NC and the MD. Compared with the MD-NC dimer, the CC1-mediated integration of NC and MD not only blocks the NC dimer formation, but also prevents the neck linker (NL) undocking and the ADP release from the MD. Mutations of the essential residues in the interdomain interaction interface in the MD-NC-CC1 monomer restored the MD activity. Thus, CC1 fastens the neck domain and MD and inhibits both NC and NL. This CC1-mediated lockdown of the entire neck domain may represent a paradigm for kinesin autoinhibition that could be applicable to other kinesin-3 motors.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Cinesinas/metabolismo , Proteínas Motores Moleculares/metabolismo , Domínios Proteicos/fisiologia , Sequência de Aminoácidos , Transporte Biológico , Linhagem Celular , Cristalografia por Raios X , Dimerização , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Mutação Puntual , Ligação Proteica , Conformação Proteica , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência
4.
Med Teach ; 42(12): 1343-1349, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32795244

RESUMO

PURPOSE: The aim of this review is to explore the effects of the seminar teaching method versus lecture-based learning (LBL) in the education of medical students by meta-analysis. METHOD: Data and information available on PubMed, Cochrane Library, EMBASE, MEDLINE, China National Knowledge Infrastructure, WanFang Data, China Science Periodical Database, and Chinese BioMedical were searched and examined from the inception up to January 2020. Randomized controlled trials (RCTs) that investigated the effects of the seminar teaching method versus LBL in medical education were included. RESULTS: A total of 16 RCTs were included, with a total sample size of 1122 medical students. The seminar teaching method significantly improved knowledge scores (SMD = 1.38, 95%CI 0.92-1.84; p < 0.001) and skill scores (SMD = 1.46, 95%CI 1.00-1.91; p < 0.001) and the seminar teaching method significantly improved teaching effects, including active learning ability, learning interest, scientific innovation, and independent thinking ability, expression and communication ability, clinical thinking ability, teamwork, teacher-student interaction, and classroom atmosphere. CONCLUSIONS: This meta-analysis showed that the seminar teaching method is an effective method for improving knowledge scores, skill scores, active learning ability, student collaboration, classroom atmosphere, and interaction between teachers and students.


Assuntos
Educação Médica , Estudantes de Medicina , China , Humanos , Aprendizagem Baseada em Problemas , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensino
5.
Zhonghua Nan Ke Xue ; 24(5): 414-418, 2018 May.
Artigo em Zh | MEDLINE | ID: mdl-30171756

RESUMO

OBJECTIVE: To evaluate the semen quality of the HIV/AIDS male patients after treated by the highly active antiretroviral therapy (HAART) and their potential of transmitting HIV/AIDS and provide some evidence for this cohort of males who wish for parenthood. METHODS: We collected semen samples from 20 HIV/AIDS male patients who had been treated by HAART for over 6 months and wished for parenthood. We examined sperm concentration, viability and total motility and the percentage of morphologically normal sperm (MNS) using the computer-assisted semen analysis system, measured the HIV-1 RNA loads in the semen by the Cobas Amplicor Monitor test, and counted CD4+ T cells in the peripheral blood by flow cytometry. RESULTS: The patients were aged 25-40 (30.7 ± 5.05) years. After treated by HAART for 6-26 (14.24 ± 12.26) months, the count of blood CD4+ T cells was significantly increased (341-1 058 ï¼»535.76 ± 212.021ï¼½ /µl) in comparison with the baseline (226-965 ï¼»422.38 ± 200.86ï¼½ /µl). Compared with the normal value, the semen volume was increased except in 1 case (≥2 ml) while total sperm motility was decreased in 13 cases (≥40%), and so were sperm concentration in 2 cases (≥15 × 106 / ml), sperm viability in 5 (58%), the percentage of progressively motile sperm in 18 (≥32%), and the percentage of MNS in 6 (≤4%). HIV-1 RNA in the peripheral blood was <20 copies/mL in all the cases and that in the seminal plasma was also <20 copies/ml in 18 cases but >20 copies/mL in the other 2 (ï¼»4.70 × 101ï¼½ and ï¼»2.2 × 102ï¼½ copies/ml, respectively). Of the 4 couples that had sex without protective measures for over 6 months, all the 4 female partners exhibited negative HIV antibodies in regular follow-up examinations and 1 achieved spontaneous pregnancy and healthy birth, with negative HIV-1 RNA in both the mother and the baby. CONCLUSIONS: The HIV RNA level is higher in the semen than in the blood of the HIV/AIDS male patients after HAART, which indicates the potential risk of their semen transmitting HIV/AIDS to their female partners. Their sperm concentration and total sperm motility are lower than the normal value, which suggests a decreased fertility.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , RNA Viral/análise , Análise do Sêmen , Adulto , Feminino , Citometria de Fluxo , Infecções por HIV/virologia , Humanos , Masculino , Gravidez , Sêmen , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatozoides , Adulto Jovem
6.
J Biol Chem ; 291(7): 3581-94, 2016 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-26680000

RESUMO

Processive kinesin motors often contain a coiled-coil neck that controls the directionality and processivity. However, the neck coil (NC) of kinesin-3 is too short to form a stable coiled-coil dimer. Here, we found that the coiled-coil (CC1)-forkhead-associated (FHA) tandem (that is connected to NC by Pro-390) of kinesin-3 KIF13A assembles as an extended dimer. With the removal of Pro-390, the NC-CC1 tandem of KIF13A unexpectedly forms a continuous coiled-coil dimer that can be well aligned into the CC1-FHA dimer. The reverse introduction of Pro-390 breaks the NC-CC1 coiled-coil dimer but provides the intrinsic flexibility to couple NC with the CC1-FHA tandem. Mutations of either NC, CC1, or the FHA domain all significantly impaired the motor activity. Thus, the three elements within the NC-CC1-FHA tandem of KIF13A are structurally interrelated to form a stable dimer for activating the motor. This work also provides the first direct structural evidence to support the formation of a coiled-coil neck by the short characteristic neck domain of kinesin-3.


Assuntos
Cinesinas/química , Modelos Moleculares , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Proteínas Relacionadas à Autofagia , Sequência Conservada , Cristalografia por Raios X , Dimerização , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Cinesinas/genética , Cinesinas/metabolismo , Camundongos , Simulação de Dinâmica Molecular , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Maleabilidade , Mutação Puntual , Conformação Proteica , Dobramento de Proteína , Estabilidade Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Sequências de Repetição em Tandem
7.
J Clin Ultrasound ; 45(3): 127-133, 2017 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-28090635

RESUMO

BACKGROUND: To determine the sonographic features of peripheral schwannomas. METHODS: This retrospective study included 54 cases of schwannoma in 51 patients. Ultrasonography (US) and MRI were performed in all patients. The US features of each tumor were analyzed and compared with pathologic findings. The US target sign was compared with the MRI findings. RESULTS: On US, 53 of the 54 schwannomas had a regular shape and clear margins, and one had an irregular shape. Thirty-seven of the 54 schwannomas were categorized as solid, 16 as cystic and solid, and one as entirely cystic; distal sound enhancement was associated with 47 schwannomas. The target sign was seen in 24, the rat tail sign in 28, the vessel accompanying sign in 22, and the split fat sign in 5. The entering and exiting nerves were situated centrally in 9 and eccentrically in 19 schwannomas. Vascularity on color Doppler imaging using a 0 to III scale was graded 0 in 4 schwannomas, I in 10, II in 26, and III in 14. Twenty-four target signs were detected in 54 schwannomas by US, and 28 were detected by MRI. There was good agreement between the target signs noted on US and those seen on MRI (κ = 0.631, p < 0.001). CONCLUSIONS: The sonographic diagnosis of peripheral schwannomas is feasible and reliable. The target sign is a prominent US feature in peripheral schwannomas, comparable to that observed with MRI. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:127-133, 2017.


Assuntos
Neurilemoma/diagnóstico por imagem , Ultrassonografia , Adolescente , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
8.
EMBO J ; 30(4): 665-78, 2011 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-21240187

RESUMO

Zonula occludens (ZO)-1 is a multi-domain scaffold protein known to have critical roles in the establishment of cell-cell adhesions and the maintenance of stable tissue structures through the targeting, anchoring, and clustering of transmembrane adhesion molecules and cytoskeletal proteins. Here, we report that ZO-1 directly binds to MRCKß, a Cdc42 effector kinase that modulates cell protrusion and migration, at the leading edge of migrating cells. Structural studies reveal that the binding of a ß hairpin from GRINL1A converts ZO-1 ZU5 into a complete ZU5-fold. A similar interaction mode is likely to occur between ZO-1 ZU5 and MRCKß. The interaction between ZO-1 and MRCKß requires the kinase to be primed by Cdc42 due to the closed conformation of the kinase. Formation of the ZO-1/MRCKß complex enriches the kinase at the lamellae of migrating cells. Disruption of the ZO-1/MRCKß complex inhibits MRCKß-mediated cell migration. These results demonstrate that ZO-1, a classical scaffold protein with accepted roles in maintaining cell-cell adhesions in stable tissues, also has an active role in cell migration during processes such as tissue development and remodelling.


Assuntos
Movimento Celular , Proteínas de Membrana/metabolismo , Fosfoproteínas/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteína cdc42 de Ligação ao GTP/fisiologia , Sequência de Aminoácidos , Animais , Células COS , Adesão Celular/genética , Adesão Celular/fisiologia , Compartimento Celular/fisiologia , Movimento Celular/genética , Movimento Celular/fisiologia , Células Cultivadas , Chlorocebus aethiops , Humanos , Proteínas de Membrana/química , Proteínas de Membrana/genética , Modelos Biológicos , Modelos Moleculares , Dados de Sequência Molecular , Complexos Multiproteicos/química , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Miotonina Proteína Quinase , Fosfoproteínas/química , Fosfoproteínas/genética , Ligação Proteica/genética , Ligação Proteica/fisiologia , Estrutura Secundária de Proteína , Transporte Proteico/genética , Transporte Proteico/fisiologia , Proteínas Tirosina Quinases/química , Proteínas Tirosina Quinases/genética , Homologia de Sequência de Aminoácidos , Transfecção , Proteína da Zônula de Oclusão-1 , Proteína cdc42 de Ligação ao GTP/química , Proteína cdc42 de Ligação ao GTP/genética , Proteína cdc42 de Ligação ao GTP/metabolismo
9.
New Phytol ; 207(3): 692-709, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25827016

RESUMO

Plant basic helix-loop-helix (bHLH) transcription factors play essential roles in abiotic stress tolerance. However, most bHLHs have not been functionally characterized. Here, we characterized the functional role of a bHLH transcription factor from Arabidopsis, AtbHLH112, in response to abiotic stress. AtbHLH112 is a nuclear-localized protein, and its nuclear localization is induced by salt, drought and abscisic acid (ABA). In addition, AtbHLH112 serves as a transcriptional activator, with the activation domain located at its N-terminus. In addition to binding to the E-box motifs of stress-responsive genes, AtbHLH112 binds to a novel motif with the sequence 'GG[GT]CC[GT][GA][TA]C' (GCG-box). Gain- and loss-of-function analyses showed that the transcript level of AtbHLH112 is positively correlated with salt and drought tolerance. AtbHLH112 mediates stress tolerance by increasing the expression of P5CS genes and reducing the expression of P5CDH and ProDH genes to increase proline levels. AtbHLH112 also increases the expression of POD and SOD genes to improve reactive oxygen species (ROS) scavenging ability. We present a model suggesting that AtbHLH112 is a transcriptional activator that regulates the expression of genes via binding to their GCG- or E-boxes to mediate physiological responses, including proline biosynthesis and ROS scavenging pathways, to enhance stress tolerance.


Assuntos
Adaptação Fisiológica/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/fisiologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Regulação da Expressão Gênica de Plantas , Motivos de Nucleotídeos/genética , Estresse Fisiológico/genética , Ácido Abscísico/farmacologia , Adaptação Fisiológica/efeitos dos fármacos , Arabidopsis/citologia , Arabidopsis/efeitos dos fármacos , Sequência de Bases , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Pressão Osmótica/efeitos dos fármacos , Plantas Geneticamente Modificadas , Prolina/metabolismo , Ligação Proteica/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Transativadores/metabolismo
10.
Pharm Stat ; 14(2): 108-19, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25641851

RESUMO

Various statistical models have been proposed for two-dimensional dose finding in drug-combination trials. However, it is often a dilemma to decide which model to use when conducting a particular drug-combination trial. We make a comprehensive comparison of four dose-finding methods, and for fairness, we apply the same dose-finding algorithm under the four model structures. Through extensive simulation studies, we compare the operating characteristics of these methods in various practical scenarios. The results show that different models may lead to different design properties and that no single model performs uniformly better in all scenarios. As a result, we propose using Bayesian model averaging to overcome the arbitrariness of the model specification and enhance the robustness of the design. We assign a discrete probability mass to each model as the prior model probability and then estimate the toxicity probabilities of combined doses in the Bayesian model averaging framework. During the trial, we adaptively allocated each new cohort of patients to the most appropriate dose combination by comparing the posterior estimates of the toxicity probabilities with the prespecified toxicity target. The simulation results demonstrate that the Bayesian model averaging approach is robust under various scenarios.


Assuntos
Teorema de Bayes , Ensaios Clínicos Fase I como Assunto/métodos , Quimioterapia Combinada/métodos , Dose Máxima Tolerável , Estudos de Coortes , Simulação por Computador , Humanos
11.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(11): 3058-62, 2015 Nov.
Artigo em Zh | MEDLINE | ID: mdl-26978908

RESUMO

Propolis possesses functions of antibacterial, antiviral, anticancer, and liver protection, and is known as the "purple gold", however, the phenomenon which making and selling of counterfeit are growing in intensity. In order to establish a authenticity and quality of propolis evaluation model, in this paper, forty-one Chinese propolis, one proplis from United States and two tree gums were used for experimental materials. The infrared spectrum collection was performed by Fourier transform infrared spectrometer, and principal component analysis (PCA) was used for data analysis. The result showed that, the intrared spectrum of propolis and tree gum were significantly different. The propolis characteristic peak only appeared in 2500-3500 and 400-1800 cm⁻¹. All propolis had two frequency region of characteristic peaks, 2849.08-2848.53 and 2917.74- 2916.76 cm⁻¹, but tree gum did not have characteristic peak in this region. The characteristic peaks of gum were in 1150-1300 and 1550-1650 cm⁻¹. Differences in these aspects can be used to distinguish propolis and gum, and can be used to identify true and false propolis. We use Qinghai propolis as a standard sample, in 42 samples, the matching degree of other propolis is > 80%. In addition, the result of PCA shows that tree gum and the propolis from different climate zone, or with different colors could be distinguished well. This paper firstly performed analysis on different propolis and gum by infrared spectrum, and a new method, for authenticity and quality of propolis identification, could be developed.


Assuntos
Gomas Vegetais/química , Própole/química , Espectroscopia de Infravermelho com Transformada de Fourier , Árvores
12.
Molecules ; 19(2): 1939-55, 2014 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-24518809

RESUMO

Celery (Apium graveolens L.) is one of the most economically important vegetables worldwide, but genetic and genomic resources supporting celery molecular breeding are quite limited, thus few studies on celery have been conducted so far. In this study we made use of simple sequence repeat (SSR) markers generated from previous celery transcriptome sequencing and attempted to detect the genetic diversity and relationships of commonly used celery accessions and explore the efficiency of the primers used for cultivars identification. Analysis of molecular variance (AMOVA) of Apium graveolens L. var. dulce showed that approximately 43% of genetic diversity was within accessions, 45% among accessions, and 22% among horticultural types. The neighbor-joining tree generated by unweighted pair group method with arithmetic mean (UPGMA), and population structure analysis, as well as principal components analysis (PCA), separated the cultivars into clusters corresponding to the geographical areas where they originated. Genetic distance analysis suggested that genetic variation within Apium graveolens was quite limited. Genotypic diversity showed any combinations of 55 genic SSRs were able to distinguish the genotypes of all 30 accessions.


Assuntos
Apium/genética , Etiquetas de Sequências Expressas , Repetições de Microssatélites/genética , Impressões Digitais de DNA , Variação Genética , Genótipo , Polimorfismo Genético
13.
Acta Crystallogr Sect E Struct Rep Online ; 70(Pt 1): o72, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24527005

RESUMO

In the title compound, 2C11H18N(+)·2PF6 (-)·C12H24O6, the 18-crown-6 mol-ecule has crystallographically imposed inversion symmetry. In the crystal, it inter-acts with the cation through weak C-H⋯O hydrogen bonds. The cations and anions are further linked via N-H⋯F and C-H⋯F hydrogen bonds, leading to a sandwich structure .

14.
J Agric Food Chem ; 72(19): 10995-11001, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38701424

RESUMO

The titer of the microbial fermentation products can be increased by enzyme engineering. l-Sorbosone dehydrogenase (SNDH) is a key enzyme in the production of 2-keto-l-gulonic acid (2-KLG), which is the precursor of vitamin C. Enhancing the activity of SNDH may have a positive impact on 2-KLG production. In this study, a computer-aided semirational design of SNDH was conducted. Based on the analysis of SNDH's substrate pocket and multiple sequence alignment, three modification strategies were established: (1) expanding the entrance of SNDH's substrate pocket, (2) engineering the residues within the substrate pocket, and (3) enhancing the electron transfer of SNDH. Finally, mutants S453A, L460V, and E471D were obtained, whose specific activity was increased by 20, 100, and 10%, respectively. In addition, the ability of Gluconobacter oxidans WSH-004 to synthesize 2-KLG was improved by eliminating H2O2. This study provides mutant enzymes and metabolic engineering strategies for the microbial-fermentation-based production of 2-KLG.


Assuntos
Proteínas de Bactérias , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Gluconobacter/enzimologia , Gluconobacter/genética , Gluconobacter/metabolismo , Açúcares Ácidos/metabolismo , Açúcares Ácidos/química , Fermentação , Engenharia de Proteínas , Engenharia Metabólica , Desidrogenases de Carboidrato/metabolismo , Desidrogenases de Carboidrato/genética , Desidrogenases de Carboidrato/química , Cinética
15.
J Biol Chem ; 287(2): 1139-49, 2012 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-22090031

RESUMO

Protein-disulfide isomerase (PDI), with domains arranged as abb'xa'c, is a key enzyme and chaperone localized in the endoplasmic reticulum (ER) catalyzing oxidative folding and preventing misfolding/aggregation of proteins. It has been controversial whether the chaperone activity of PDI is redox-regulated, and the molecular basis is unclear. Here, we show that both the chaperone activity and the overall conformation of human PDI are redox-regulated. We further demonstrate that the conformational changes are triggered by the active site of domain a', and the minimum redox-regulated cassette is located in b'xa'. The structure of the reduced bb'xa' reveals for the first time that domain a' packs tightly with both domain b' and linker x to form one compact structural module. Oxidation of domain a' releases the compact conformation and exposes the shielded hydrophobic areas to facilitate its high chaperone activity. Thus, the study unequivocally provides mechanistic insights into the redox-regulated chaperone activity of human PDI.


Assuntos
Chaperonas Moleculares/química , Isomerases de Dissulfetos de Proteínas/química , Dobramento de Proteína , Humanos , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Oxirredução , Isomerases de Dissulfetos de Proteínas/genética , Isomerases de Dissulfetos de Proteínas/metabolismo , Estrutura Terciária de Proteína
16.
Biochem Biophys Res Commun ; 435(3): 441-6, 2013 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-23669038

RESUMO

KIF1A, a member of kinesin-3 motors, plays a pivotal role in anterograde axonal transport of synaptic vesicles (SVs). We have shown that the CC1-FHA tandem of KIF1A forms a stable dimer that is crucial for both the dimerization and activation of the motor. However, it remains to be determined whether the CC1-FHA dimer is essential for KIF1A-mediated axonal transport in vivo. Here, we use Caenorhabditis elegans as the model organism to probe the in vivo function of the CC1-FHA dimer. Disruption of the CC1-FHA dimer severely impairs the KIF1A-mediated regulation of the locomotion and pumping behavior of C. elegans and exerts a significant impact on KIF1A-mediated axonal SV transport. Thus, together with previous structural and biochemical studies, the in vivo data presented in this study firmly establish the essential role of the CC1-FHA dimer for KIF1A-mediated neuronal transport.


Assuntos
Transporte Axonal/genética , Proteínas de Caenorhabditis elegans/fisiologia , Caenorhabditis elegans/fisiologia , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/fisiologia , Vesículas Sinápticas/química , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/genética , Movimento/fisiologia , Proteínas do Tecido Nervoso/genética , Domínios e Motivos de Interação entre Proteínas , Multimerização Proteica , Estabilidade Proteica , Vesículas Sinápticas/genética
17.
Zhongguo Zhen Jiu ; 43(6): 727-32, 2023 Jun 12.
Artigo em Zh | MEDLINE | ID: mdl-37313570

RESUMO

This paper reviews the researches on acupuncture preconditioning before surgery in recent years and explores its application value from three aspects, i.e. relieving preoperative anxiety, preventing from postoperative cognitive dysfunction, and preventing from postoperative gastrointestinal dysfunction. As a relatively safe non-drug treatment, acupuncture has the underlying advantages in participating into multidisciplinary coordination in the enhanced recovery after surgery (ERAS). By building up higher-quality medical evidences and revealing the effect mechanism of acupuncture from multi-dimenisonal aspects, it is expected that acupuncture technology can be coordinated with ERAS to optimize the clinical path in the perioperative period, and boost the development of the perioperative medicine ultimately.


Assuntos
Terapia por Acupuntura , Recuperação Pós-Cirúrgica Melhorada , Humanos , Ansiedade , Transtornos de Ansiedade , Período Perioperatório
18.
J Cell Sci ; 123(Pt 22): 3933-43, 2010 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-20980394

RESUMO

In eukaryotes, replication licensing is achieved through sequential loading of several replication-initiation proteins onto replication origins to form pre-replicative complexes (pre-RCs), and unscheduled replication licensing is prevented by cyclin-dependent kinases (CDKs) through inhibitory phosphorylations of multiple initiation proteins. It is known that CDK inactivation during mitotic exit promotes pre-RC formation for the next cell cycle. However, whether the removal of the inhibitory phosphorylations on the initiation proteins is essential and the identity of the acting phosphatase(s) remain unknown. Here, we show that cell division cycle protein 14 (Cdc14p) dephosphorylates replication-initiation proteins Orc2p, Orc6p, Cdc6p and Mcm3p to restore their competence for pre-RC assembly in the budding yeast Saccharomyces cerevisiae. Cells without functional Cdc14p fail to dephosphorylate initiation proteins and to form pre-RCs - even when CDK activities are suppressed - and cannot replicate DNA in mitotic rereplication systems, whereas pulsed ectopic expression of Cdc14p in mitotic cells results in efficient pre-RC assembly and DNA rereplication. Furthermore, Cdc14p becomes dispensable for DNA rereplication in mitotic cells with combined non-phosphorylatable and/or phosphorylation-insensitive alleles of the initiation proteins. These data unravel the essential role of Cdc14p in replication licensing, beyond its established functions in mitotic exit, providing new insight into the intricate regulation of DNA replication through the interplay of CDKs and the Cdc14p phosphatase.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Replicação do DNA/fisiologia , Proteínas Tirosina Fosfatases/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/metabolismo , Ciclo Celular/fisiologia , Núcleo Celular/genética , Núcleo Celular/metabolismo , DNA Fúngico/biossíntese , DNA Fúngico/genética , Mitose/fisiologia , Fosforilação , Origem de Replicação , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética
19.
IEEE Trans Cybern ; 52(8): 7441-7452, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33400668

RESUMO

Automatically generating an accurate and meaningful description of an image is very challenging. However, the recent scheme of generating an image caption by maximizing the likelihood of target sentences lacks the capacity of recognizing the human-object interaction (HOI) and semantic relationship between HOIs and scenes, which are the essential parts of an image caption. This article proposes a novel two-phase framework to generate an image caption by addressing the above challenges: 1) a hybrid deep learning and 2) an image description generation. In the hybrid deep-learning phase, a novel factored three-way interaction machine was proposed to learn the relational features of the human-object pairs hierarchically. In this way, the image recognition problem is transformed into a latent structured labeling task. In the image description generation phase, a lexicalized probabilistic context-free tree growing scheme is innovatively integrated with a description generator to transform the descriptions generation task into a syntactic-tree generation process. Extensively comparing state-of-the-art image captioning methods on benchmark datasets, we demonstrated that our proposed framework outperformed the existing captioning methods in different ways, such as significantly improving the performance of the HOI and relationships between HOIs and scenes (RHIS) predictions, and quality of generated image captions in a semantically and structurally coherent manner.


Assuntos
Algoritmos , Idioma , Humanos , Semântica
20.
Comput Intell Neurosci ; 2022: 7592258, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35875772

RESUMO

As a new generative model, the generative adversarial network (GAN) has great potential in the accuracy and efficiency of generating pseudoreal data. Nowadays, bearing fault diagnosis based on machine learning usually needs sufficient data. If enough near-real data can be generated in the case of insufficient samples in the actual operating condition, the effect of fault diagnosis will be greatly improved. In this study, a new rolling bearing data generation method based on the generative adversarial network (GAN) is proposed, which can be trained adversarially and jointly via a learned embedding, and applied to solve fault diagnosis problems with insufficient data. By analyzing the time-domain characteristics of rolling bearing life cycle monitoring data in actual working conditions, the operation data are divided into three periods, and the construction and training of the generative adversarial network model are carried out. Data generated by adversarial are compared with the real data in the time domain and frequency domain, respectively, and the similarity between the generated data and the real data is verified.


Assuntos
Aprendizado de Máquina
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