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CP74 is an engineered circular permutant of a deep trefoil knotted SpoU-TrmD (SPOUT) RNA methyl transferase protein YbeA from E. coli. We have previously established that the circular permutation unties the knotted topology of YbeA and CP74 forms a domain-swapped dimer with a large dimeric interface of ca. 4600 Å2. To understand the impact of domain-swapping and the newly formed hinge region joining the two folded domains on the folding and stability of CP74, the five equally spaced tryptophan residues were individually substituted into phenylalanine to monitor their conformational and stability changes by a battery of biophysical tools. Far-UV circular dichroism, intrinsic fluorescence, and small-angle X-ray scattering dictated minimal global conformational perturbations to the native structures in the tryptophan variants. The structures of the tryptophan variants also showed the conservation of the domain-swapped ternary structure with the exception that the W72F exhibited significant asymmetry in the α-helix 5. Comparative global thermal and chemical stability analyses indicated the pivotal role of W100 in the folding of CP74 followed by W19 and W72. Solution-state NMR spectroscopy and hydrogen-deuterium exchange mass spectrometry further revealed the accumulation of a native-like intermediate state in which the hinge region made important contributions to maintain the domain-swapped ternary structure of CP74.
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Escherichia coli , Dobramento de Proteína , Dicroísmo Circular , Cinética , Proteínas , TriptofanoRESUMO
BACKGROUND: Surgical resection remains the primary treatment for hepatic malignancies, and intraoperative bleeding is associated with a significantly increased risk of death. Therefore, accurate prediction of intraoperative bleeding risk in patients with hepatic malignancies is essential to preventing bleeding in advance and providing safer and more effective treatment. AIM: To develop a predictive model for intraoperative bleeding in primary hepatic malignancy patients for improving surgical planning and outcomes. METHODS: The retrospective analysis enrolled patients diagnosed with primary hepatic malignancies who underwent surgery at the Hepatobiliary Surgery Department of the Fourth Hospital of Hebei Medical University between 2010 and 2020. Logistic regression analysis was performed to identify potential risk factors for intraoperative bleeding. A prediction model was developed using Python programming language, and its accuracy was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Among 406 primary liver cancer patients, 16.0% (65/406) suffered massive intraoperative bleeding. Logistic regression analysis identified four variables as associated with intraoperative bleeding in these patients: ascites [odds ratio (OR): 22.839; P < 0.05], history of alcohol consumption (OR: 2.950; P < 0.015), TNM staging (OR: 2.441; P < 0.001), and albumin-bilirubin score (OR: 2.361; P < 0.001). These variables were used to construct the prediction model. The 406 patients were randomly assigned to a training set (70%) and a prediction set (30%). The area under the ROC curve values for the model's ability to predict intraoperative bleeding were 0.844 in the training set and 0.80 in the prediction set. CONCLUSION: The developed and validated model predicts significant intraoperative blood loss in primary hepatic malignancies using four preoperative clinical factors by considering four preoperative clinical factors: ascites, history of alcohol consumption, TNM staging, and albumin-bilirubin score. Consequently, this model holds promise for enhancing individualised surgical planning.
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Noisy labels are often encountered in datasets, but learning with them is challenging. Although natural discrepancies between clean and mislabeled samples in a noisy category exist, most techniques in this field still gather them indiscriminately, which leads to their performances being partially robust. In this paper, we reveal both empirically and theoretically that the learning robustness can be improved by assuming deep features with the same labels follow a student distribution, resulting in a more intuitive method called student loss. By embedding the student distribution and exploiting the sharpness of its curve, our method is naturally data-selective and can offer extra strength to resist mislabeled samples. This ability makes clean samples aggregate tightly in the center, while mislabeled samples scatter, even if they share the same label. Additionally, we employ the metric learning strategy and develop a large-margin student (LT) loss for better capability. It should be noted that our approach is the first work that adopts the prior probability assumption in feature representation to decrease the contributions of mislabeled samples. This strategy can enhance various losses to join the student loss family, even if they have been robust losses. Experiments demonstrate that our approach is more effective in inaccurate supervision. Enhanced LT losses significantly outperform various state-of-the-art methods in most cases. Even huge improvements of over 50% can be obtained under some conditions.
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Cytokine-mediated STAT5 protein activation is vital for lymphocyte development and function. In vitro tyrosine phosphorylation of a C-terminal tyrosine is critical for activation of STAT5A and STAT5B; however, the importance of STAT5 tyrosine phosphorylation in vivo has not been assessed. Here we generate Stat5a and Stat5b tyrosine-to-phenylalanine mutant knockin mice and find they have greatly reduced CD8+ T-cell numbers and profoundly diminished IL-2-induced proliferation of these cells, and this correlates with reduced induction of Myc, pRB, a range of cyclins and CDKs, and a partial G1âS phase-transition block. These mutant CD8+ T cells also exhibit decreased IL-2-mediated activation of pERK and pAKT, which we attribute in part to diminished expression of IL-2Rß and IL-2Rγ. Our findings thus demonstrate that tyrosine phosphorylation of both STAT5A and STAT5B is essential for maximal IL-2 signaling. Moreover, our transcriptomic and proteomic analyses elucidate the molecular basis of the IL-2-induced proliferation of CD8+ T cells.
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Linfócitos T CD8-Positivos , Proliferação de Células , Interleucina-2 , Fator de Transcrição STAT5 , Transdução de Sinais , Tirosina , Fator de Transcrição STAT5/metabolismo , Fator de Transcrição STAT5/genética , Animais , Interleucina-2/metabolismo , Fosforilação , Tirosina/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Camundongos , Subunidade beta de Receptor de Interleucina-2/metabolismo , Subunidade beta de Receptor de Interleucina-2/genética , Subunidade gama Comum de Receptores de Interleucina/genética , Subunidade gama Comum de Receptores de Interleucina/metabolismo , Camundongos Endogâmicos C57BL , Técnicas de Introdução de Genes , Ativação LinfocitáriaRESUMO
BACKGROUND: Sleep deprivation (SD) among young adults is a major public health concern. In humans, it has adverse effects on mood and results in serious health problems. Faced with SD, persons may take precautionary measures to try and reduce their risk. The aim of this study is to evaluate the efficacy and safety of electroacupuncture (EA) for the prevention of negative moods after SD. In addition, we will do a comparison of the effects of EA on mood after SD at different time points. METHODS: This randomized controlled trial (RCT) will be performed at the First Affiliated Hospital of Changchun University of Chinese Medicine in China. The Standards for Reporting Interventions in Clinical Trials of Acupuncture 2010 will be strictly adhered to. Forty-two healthy male volunteers will be distributed into acupoints electroacupuncture (AE) group, non-acupoints electroacupuncture (NAE) control group, or blank control group. This trial will comprise 1-week baseline (baseline sleep), 1-week preventative treatment, 30-h total sleep deprivation (TSD), and 24-h after waking follow-up period. Participants in the AE group and the NAE control group during the preventative treatment period will be administered with EA treatment once daily for 1 week. Participants in the blank control group will not be administered with any treatment. The primary outcome will be the Profile of Mood States (POMS) Scale. Secondary outcome measures will include changes in the Noldus FaceReader (a tool for automatic analysis of facial expressions) and Positive and Negative Affect Schedule (PANAS) Scale. Total sleep deprivation will be 30 h. During the 30-h TSD period, participants will be subjected to 11 sessions of assessment. Adverse events will be recorded. DISCUSSION: This study is designed to evaluate the efficacy and safety of EA for the prevention of negative moods after SD. The results of this trial will allow us to compare the effects of EA on mood after SD at different time points. Moreover, the findings from this trial will be published in peer-reviewed journals. TRIAL REGISTRATION: Chinese Clinical Trial Registry Chi2000039713 . Registered on 06 November 2020.
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Eletroacupuntura , Pontos de Acupuntura , Eletroacupuntura/efeitos adversos , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Privação do Sono/diagnóstico , Privação do Sono/etiologia , Privação do Sono/prevenção & controle , Resultado do Tratamento , Adulto JovemRESUMO
It is an important precondition to retrieve the ground surface reflectance exactly for improving the subsequent product of remote sensing images and the quantitative application of remote sensing. However, because the electromagnetic wave is scattered by the atmosphere during its transmission from the ground surface to the sensor, the electromagnetic wave signal of the target received by the sensor contained the signal of the background. The adjacency effect emerges. Because of the adjacency effect, the remote sensing images become blurry, and their contrast reduces. So the ground surface reflectance retrieved from the remote sensing images is also inaccurate. Finally, the quality of subsequent product of remote sensing images and the accuracy of quantitative application of remote sensing might decrease. In the present paper, according to the radiative transfer equation, the atmospheric adjacency effect correction experiment of ETM images was carried out by using the point spread function method. The result of the experiment indicated that the contrast of the corrected ETM images increased, and the ground surface reflectance retrieved from those images was more accurate.
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In this study, an S-doped g-C3N4 nanosheet was prepared as a photocatalyst for effective oxygen evolution reaction. Sulfur plays a crucial role in S-doped g-C3N4 not only in increasing the charge density but also in reducing the energy band gap of S-doped g-C3N4 via substitution of nitrogen sites. S-doped g-C3N4 can serve as an oxygen-evolved photocatalyst, when combined with Ru/SrTiO3:Rh in the presence of [Co(bpy)3]3+/2+ as an electron mediator, enables photocatalytic overall water splitting under visible light irradiation with hydrogen and oxygen production rates of 24.6 and 14.5⯵mol-h-1, respectively. Moreover, the photocatalytic overall water splitting to produce H2 and O2 using this Z-scheme system could use for five runs to at least 94.5â¯h under visible light irradiation. On the other hand, S-doped g-C3N4 can reduce biofouling by bacteria such as Escherichia coli by more than 70%, by simply incubating the S-doped g-C3N4 sample with bacterial solution under light irradiation. Our results suggest that S-doped g-C3N4 is a potentially effective, green, and promising material for a variety of photocatalytic applications.
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Incrustação Biológica/prevenção & controle , Escherichia coli/efeitos dos fármacos , Grafite/farmacologia , Nanopartículas/química , Compostos de Nitrogênio/farmacologia , Água/química , Catálise , Escherichia coli/metabolismo , Grafite/química , Hidrogênio/química , Compostos de Nitrogênio/química , Oxigênio/química , Tamanho da Partícula , Processos Fotoquímicos , Propriedades de SuperfícieRESUMO
This study reports a new microfluidic system integrated with a microfluidic control module and a micro electrochemical module for detection of urinary proteins. The integrated microsystem can automatically detect proteins in urine with a high sensitivity. The microfluidic control module consists of a new two-way, spiral-shape micropump which can transport the urine samples to the sensing regions. The net ionic charges of the protein samples can be detected while the samples flow through the sensing region of the micro electrochemical module. Two major urinary proteins including lysozyme and albumin are detected in a multiple-channel layout with little human intervention and are analyzed in a short period of time, while only consuming a 100-mul urine sample. The developed microfluidic system could lead to a convenient, yet crucial, platform for chemical and biological detection and diagnosis.
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Albuminas/análise , Albuminúria/urina , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Muramidase/urina , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Humanos , Sensibilidade e EspecificidadeRESUMO
In the condition that the DN(Digital Number) value images of ground-atmosphere system recorded by the QuickBird artificial satellite sensor were taken as the experimental datum, the equation of pixel decomposition was structured, abiding by energy conservation law and the proportional relationship between the sum of 1-4 band integral radiance and the panchromatic band (Pan) integral radiance. By using the equation gained above, every pixel of 1-4 band images was decomposed into sixteen pixels. So the high resolution 1-4 band radiance images with the resolution of 0.61 m were finally obtained in this experiment. Compared with the original 1-4 band images, the spatial resolution of the high resolution 1-4 band radiance images was raised by four times. The detailed characteristics of the surface features in the high resolution 1-4 band radiance images were more limpid than the original 1-4 band images. The optesthesia effect was also improved obviously in the high resolution 1-4 band radiance images. Therefore, the map with appropriate scale improved from 1 : 10 000 to 1 : 2 500 can be made based on the high resolution 1-4 band radiance images.
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OBJECTIVE: To explore the changes of the concentration of serum ischemia modified albumin (IMA) and high sensitivity C-reactive protein (hs-CRP) in type 2 diabetic patients with retinopathy (DR). METHODS: The concentration of serum IMA and hs-CRP in DR patients were determined by ELISA and rate nephelometry and compared with those in 83 no-DR (NDR) patients and 72 controls. The concentration of serum IMA and hs-CRP in 40 proliferative diabetic retinopathy (PDR) patients were compared with those in 39 no-PDR (NPDR) patients. Data was evaluated using analysis of PPMS version 1.5.Results are expressed as means + or - standard deviation of the mean. Statistical comparisons were performed by student's t-test or one-way analysis of variance followed by Dunnett's multiple comparison test and the means compared each other using q test. RESULTS: The serum IMA and hs-CRP concentration in DR patients were (46.51 + or - 13.29) microg/L, (4.27 + or - 2.24) mg/L. The serum IMA and hs-CRP concentration in NDR patients were (25.47 + or - 9.33) microg/L, (2.96 + or - 1.84) mg/L. The serum IMA and hs-CRP concentration in controls were (15.36 + or - 4.27) microg/L, (1.86 + or - 0.97) mg/L. The serum IMA and hs-CRP concentration in PDR patients were (54.72 + or - 15.61) microg/L, (6.34 + or - 3.53) mg/L. The serum IMA and hs-CRP concentration in NPDR patients were (38.35 + or - 11.27) microg/L, (3.28 + or - 1.77) mg/L. The serum IMA and hs-CRP concentration were significantly higher in DR patients than those in controls and NDR patients, the serum IMA and hs-CRP concentration in NDR patients were significantly higher than those in controls (F = 197.124, 34.561;q = 5.41-27.34; P < 0.01); the serum IMA and hs-CRP concentration were significantly higher in PDR patients than those in NPDR patients (t = 5.46, 4.89; P < 0.01); there was significant positive correlation between serum IMA concentration and hs-CRP concentration in DR patients (r = 0.617, P < 0.01). CONCLUSION: The serum IMA and hs-CRP concentration were significantly high in DR patients, and were positively associated with the seriousness of DR, which may contribute to the development of DR.
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Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/sangue , Retinopatia Diabética/sangue , Albumina Sérica/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Isquemia/sangue , Pessoa de Meia-IdadeRESUMO
This study reports a new microfluidic system with three integrated functional devices for pumping, mixing and separation of bio-samples by utilizing micro-electro-mechanical-systems technology. By using antibody-conjugated magnetic beads, the developed system can be used to purify and enrich virus samples such that the subsequent detection of viruses can be performed with a higher sensitivity. The target viruses were first captured by the antibody coated onto the magnetic beads by using a rotary micromixer which performed the incubation process. The viruses were then purified and enriched by a magnetic field generated by planar microcoils. The integrated microfluidic system can perform the whole purification and enrichment process automatically using a rotary micropump and appropriate microvalves. In addition, a numerical simulation was also employed to optimize the design of the microcoils and to investigate the magnetic field strength and distribution. The simulation results were consistent with experimental observations. Finally, the developed system was used to successfully perform the purification and enrichment of Dengue viruses. The detectable limit of Dengue viruses was found to be as low as 10(2) pfu ml(-1) by using this approach. Therefore, the integrated microsystem can perform incubation, transportation, mixing and purification of virus samples, possibly making it a promising platform for future biological and medical applications.
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Magnetismo , Microfluídica , Vírus/química , Anticorpos/química , Simulação por Computador , Vírus da Dengue/química , Desenho de Equipamento , Técnicas Analíticas Microfluídicas , Microscopia Eletrônica de Varredura , Modelos Teóricos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Silício/química , Temperatura , Fatores de TempoRESUMO
This study describes a simple method for the selective and sensitive detection of cyanide and endogenous biological cyanide using polysorbate 40-stabilized gold nanoparticles.
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Colorimetria/métodos , Cianetos/análise , Glicosídeos/análise , Ouro/química , Nanopartículas Metálicas/química , Polissorbatos/química , Manihot/química , Sais/químicaRESUMO
The interleukin 7 receptor alpha-chain (IL-7Ralpha) is essential for T cell development in both humans and mice and for B cell development in mice. Whereas the transcription factor PU.1 regulates IL-7Ralpha expression in mouse pro-B cells via a GGAA motif, we demonstrate here that GA binding protein (GABP) bound to this site and was essential in the regulation of IL-7Ralpha expression in T cells, where PU.1 is not expressed. Moreover, IL-7Ralpha expression was diminished substantially in thymocytes but was normal on B220(+) fetal liver cells from mouse embryos with diminished expression of GABPalpha. Thus, GABP is essential for the regulation of IL-7Ralpha expression in T cells, and the differential regulation of IL-7Ralpha in distinct lymphoid lineages is achieved at least in part by differential recruitment of factors to the same GGAA motif.