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2.
Nat Chem Biol ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31819272

RESUMO

The anticancer agent indisulam inhibits cell proliferation by causing degradation of RBM39, an essential mRNA splicing factor. Indisulam promotes an interaction between RBM39 and the DCAF15 E3 ligase substrate receptor, leading to RBM39 ubiquitination and proteasome-mediated degradation. To delineate the precise mechanism by which indisulam mediates the DCAF15-RBM39 interaction, we solved the DCAF15-DDB1-DDA1-indisulam-RBM39(RRM2) complex structure to a resolution of 2.3 Å. DCAF15 has a distinct topology that embraces the RBM39(RRM2) domain largely via non-polar interactions, and indisulam binds between DCAF15 and RBM39(RRM2), coordinating additional interactions between the two proteins. Studies with RBM39 point mutants and indisulam analogs validated the structural model and defined the RBM39 α-helical degron motif. The degron is found only in RBM23 and RBM39, and only these proteins were detectably downregulated in indisulam-treated HCT116 cells. This work further explains how indisulam induces RBM39 degradation and defines the challenge of harnessing DCAF15 to degrade additional targets.

3.
Comput Methods Programs Biomed ; : 105121, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31623863

RESUMO

BACKGROUND AND OBJECTIVE: Medical image segmentation plays an important role in many clinical applications such as disease diagnosis, surgery planning, and computer-assisted therapy. However, it is a very challenging task due to variant images qualities, complex shapes of objects, and the existence of outliers. Recently, researchers have presented deep learning methods to segment medical images. However, these methods often use the high-level features of the convolutional neural network directly or the high-level features combined with the shallow features, thus ignoring the role of the global context features for the segmentation task. Consequently, they have limited capability on extensive medical segmentation tasks. The purpose of this work is to devise a neural network with global context feature information for accomplishing medical image segmentation of different tasks. METHODS: The proposed global context network (GC-Net) consists of two components; feature encoding and decoding modules. We use multiple convolutions and batch normalization layers in the encoding module. On the other hand, the decoding module is formed by a proposed global context attention (GCA) block and squeeze and excitation pyramid pooling (SEPP) block. The GCA module connects low-level and high-level features to produce more representative features, while the SEPP module increases the size of the receptive field and the ability of multi-scale feature fusion. Moreover, a weighted cross entropy loss is designed to better balance the segmented and non-segmented regions. RESULTS: The proposed GC-Net is validated on three publicly available datasets and one local dataset. The tested medical segmentation tasks include segmentation of intracranial blood vessel, retinal vessels, cell contours, and lung. Experiments demonstrate that, our network outperforms state-of-the-art methods concerning several commonly used evaluation metrics. CONCLUSION: Medical segmentation of different tasks can be accurately and effectively achieved by devising a deep convolutional neural network with a global context attention mechanism.

4.
Cryobiology ; 87: 32-39, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30876909

RESUMO

Lipid rafts and associated membrane proteins (flotillin, caveolin) play important roles in cell signaling and sperm fertilization while heat shock proteins (Hsp) ensure properly protein folding to fulfill their physiological functions. The markedly reduced fertility in thawed sperm after cryopreservation could result from disrupted membrane lipid rafts and these proteins. To explore the effect of sperm cryopreservation on lipid rafts and heat shock proteins, we compared lipid raft integrity, and the expression levels of lipid raft associated proteins (Flot-1, Flot-2, Cav-1) as well as heat shock proteins (Hsp90, Hsp70) in fresh and thawed sperm cryopreserved under different scenarios in yellow catfish. We found higher lipid raft integrity, higher protein expression levels of Flot-1, Flot-2, Cav-1, Hsp90, and Hsp70 in fresh sperm samples than in thawed sperm samples, in thawed sperm samples cryopreserved with optimal cooling rate than those cryopreserved with sub-optimal cooling rate, and in thawed sperm samples cryopreserved with extenders supplemented with cholesterol than those supplemented with methyl-ß-cyclodextrin (for cholesterol removal). Our findings indicate that lipid raft integrity, and expression levels of Flot-1, Flot-2, Cav-1, Hsp90, and Hsp70 are clearly associated with sperm quality, and together they may play a cumulative role in reduced fertility associated with thawed sperm in aquatic species.

5.
J Colloid Interface Sci ; 537: 486-495, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30469117

RESUMO

Carbon aerogels with excellent conductive characteristics and high specific capacitance have attracted more and more interests for next-generation energy storage applications. Three-dimensional interconnected Mn2O3/carbon aerogel supercapacitor electrodes are prepared by a novel doping method using MnO2 coordinated by N, N-dimethylmethanamide (DMF). The coordinative MnO2 (DMF/MnO2) plays a key role in the sol-gel process of resorcinol and formaldehyde. The doped carbon aerogels exhibits a high specific surface area of 859 m2 g-1 and a good pore-size distribution of 10-15 nm. All of the doped carbon aerogels exhibit higher specific capacitance than pure carbon aerogels, and the highest specific capacitance (170 F g-1), at current density of 1.0 A g-1, is obtained in Mn-CA-5% when 5 mol% DMF/MnO2 is added to the precursor solution. The specific capacitance is as high as 100 F g-1, at current density of 10.0 A g-1, and 97% of initial capacitance is retained over 1000 cycles at a current density of 5.0 A g-1. The doped carbon aerogels exhibits a high coulombic efficiency (up to 99.8%) and a good rate capability. The corresponding result is due to the novel doping method of DMF/MnO2 addition.

6.
Materials (Basel) ; 11(11)2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30441789

RESUMO

Environmental problems caused by metal ions have caused widespread concern in recent years. In this work, carbon aerogels (CAs) adsorbing different metal ions were prepared. The adsorption performance and kinetics of metal ions (Cu(II), Cr(VI), and Fe(III)) on carbon aerogels were systematically investigated. The results indicated that the maximum adsorption capacity of Cu(II) was 424 mg·g-1 in 600 mg·L-1 copper solution. Adsorption performances of Cu(II), Cr(VI), and Fe(III) on CAs well fitted with a pseudo-second-order kinetic model. The structures and morphologies of metal-containing samples were characterized by scanning electron micrographs (SEM), Energy Dispersive Spectrometer (EDS), transmission electron microscope (TEM), and X-ray diffraction (XRD). The results demonstrated that the texture and electrochemical performance of CAs adsorbing metal ions exhibited a clear change. The specific surface area of CAs for adsorbing copper ions was 450 m²·g-1 and they showed a small average pore diameter (7.16 nm). Furthermore, CAs adsorbing metals could be used for the super capacitor. The specific capacitance of CAs adsorbing copper ions could reach 255 F·g-1 at a current density of 1.0 A·g-1. The CA-Cu electrode materials exhibited excellent reversibility with a cycling efficiency of 97% after 5000 cycles.

7.
Oncotarget ; 8(70): 115254-115269, 2017 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-29383157

RESUMO

Pharmacological targeting of breast cancer stem cells (CSCs) is highly promising for the treatment of breast cancer, as the small population of CSCs is responsible for tumor initiation, progression, recurrence and chemo-resistance. Celecoxib is one of the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs), which have chemo-preventive activity against cancers, including breast cancer and colorectal cancer. However, the mechanisms by which NSAIDs exert its cancer prevention effects have yet been completely understood. In the present study, we investigated for the first time the effect of celecoxib on breast CSCs inhibition and its potential molecular mechanisms. Our results demonstrated that celecoxib suppresses CSC self-renewal, sensitizes chemo-resistance, inhibits epithelial to mesenchymal transition (EMT), and attenuates metastasis and tumorigenesis. Further exploring the underlying mechanism revealed that celecoxib targets breast CSCs by inhibiting the synthesis of prostaglandin E2 and down-regulating the Wnt pathway activity. Our findings suggest that celecoxib, by targeting CSCs, may be used as an adjuvant chemotherapy drug to improve breast cancer treatment outcomes.

8.
Rev Sci Instrum ; 87(3): 035103, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27036815

RESUMO

At present, conducting standard lightning impulse (LI) tests in the field for gas-insulated switchgear (GIS) equipment is difficult because of the high capacitance of the test equipment and large circuit inductance of traditional impulse devices, which leads to a wavefront time T(f) ≥ 2.5 µs. A novel fully enclosed, compact standard LI generator for testing ultra-high-voltage-class GIS equipment with high capacitance is presented to solve the problem of T(f) exceeding the standard during LI voltage tests for actual large-sized equipment. The impulse generator is installed in a metal vessel filled with SF6 or SF6/N2 gas mixture at a pressure of 0.3-0.5 MPa, providing a more compact structure and a lower series inductance. A newly developed conical voltage sensor is used to accurately measure the output voltage waveform. Two test modes (via bushing docking and direct docking) for the GIS test based on the impulse generator are introduced. Calculation results show that the impulse generator can generate an LI test waveform following the present IEC standard for the test of equipment with capacitance >10,000 pF.

9.
Zhonghua Nan Ke Xue ; 21(11): 997-1000, 2015 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-26738326

RESUMO

OBJECTIVE: To study the clinical value and operation skills of nasal endoscopy-assisted bulboprostatic anastomosis in the treatment of posterior urethral stricture. METHODS: Between January 2012 and November 2014, we performed nasal endoscopy-assisted bulboprostatic anastomosis for 12 male patients with posterior urethral stricture. We recorded the operation time, blood loss, exposure of operation visual field, and success rate of anastomosis and summarized the operation skills. RESULTS: Eight of the patients experienced first-stage recovery. Two underwent a urethral dilation at 3 months postoperatively, 1 received 10 urethral dilations within 5 months after surgery, and 1 underwent internal urethrotomy after failure in urethral dilation, but all the 4 cases were cured. CONCLUSION: Nasal endoscopy can significantly improve the operation field exposure, elevate the precision, reduce the difficulty, and enhance the efficiency of bulboprostatic anastomosis in the treatment of posterior urethral stricture.


Assuntos
Anastomose Cirúrgica , Endoscopia , Estreitamento Uretral/cirurgia , Humanos , Masculino , Duração da Cirurgia , Período Pós-Operatório , Uretra/patologia , Uretra/cirurgia
10.
J Med Chem ; 56(20): 8163-82, 2013 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-24069953

RESUMO

Hepatitis C virus (HCV) is a major global public health problem. While the current standard of care, a direct-acting antiviral (DAA) protease inhibitor taken in combination with pegylated interferon and ribavirin, represents a major advancement in recent years, an unmet medical need still exists for treatment modalities that improve upon both efficacy and tolerability. Toward those ends, much effort has continued to focus on the discovery of new DAAs, with the ultimate goal to provide interferon-free combinations. The RNA-dependent RNA polymerase enzyme NS5B represents one such DAA therapeutic target for inhibition that has attracted much interest over the past decade. Herein, we report the discovery and optimization of a novel series of inhibitors of HCV NS5B, through the use of structure-based design applied to a fragment-derived starting point. Issues of potency, pharmacokinetics, and early safety were addressed in order to provide a clinical candidate in fluoropyridone 19.


Assuntos
Antivirais/farmacologia , Inibidores Enzimáticos/farmacologia , RNA Replicase/antagonistas & inibidores , Proteínas não Estruturais Virais/antagonistas & inibidores , Animais , Antivirais/química , Antivirais/farmacocinética , Área Sob a Curva , Linhagem Celular Tumoral , Cães , Descoberta de Drogas/métodos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacocinética , Hepacivirus/efeitos dos fármacos , Hepacivirus/enzimologia , Hepacivirus/fisiologia , Hepatite C/prevenção & controle , Hepatite C/virologia , Interações Hospedeiro-Patógeno/genética , Humanos , Modelos Moleculares , Terapia de Alvo Molecular/métodos , Ligação Proteica , Estrutura Terciária de Proteína , Piridonas/síntese química , Piridonas/farmacocinética , Piridonas/farmacologia , RNA Replicase/química , RNA Replicase/metabolismo , Ratos , Relação Estrutura-Atividade , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo
11.
Guang Pu Xue Yu Guang Pu Fen Xi ; 32(4): 1028-31, 2012 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-22715778

RESUMO

Based on the characteristic of high speed line scanning for CCD in transient spectrum detection, a method of transient spectrum detection with array CCD is presented. The high speed line scanning with array CCD was realized by changing the mode of charge transfer. In order to explore the feasibility of this method, a fast detection system of single point based on linear CCD was designed and fabricated. Seven different LED pulses were measured when the system worked at fast detection mode of single point and normal mode respectively. The results demonstrate that the method of fast detection of single point based on linear CCD is feasible, and the rate of single point detection reaches up to 20 MHz. Thus, in theory, it was proved that transient spectrum detection with array CCD by changing the mode of charge transfer is also feasible.

12.
Telemed J E Health ; 17(7): 584-8, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21749261

RESUMO

China has been implementing regional collaborative medical service (also known as e-health) for >5 years, but is still facing the challenges of bridging different community health information systems (CHISs). The fact that different communities have different systems makes it difficult to share information and data between different CHISs. To explore a solution for addressing this problem, we constructed a demonstration CHIS in Beijing's Dongcheng District. This system is based on the Software-as-a-Service model, in which a central data center is used to store users' health records and to provide different services. This system provides a comprehensive platform combining disease prevention, health protection, medical care, rehabilitation, health education, and family planning. In this article, we first show the challenge of implementing e-health-oriented CHIS in China, then we briefly introduce our solution, and finally we share our experience learned from the modern CHIS implementation practice.


Assuntos
Sistemas de Informação/normas , Sistemas Computadorizados de Registros Médicos/normas , Integração de Sistemas , Telemedicina , China , Humanos
13.
Telemed J E Health ; 17(2): 76-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21250829

RESUMO

This article presents the design and applications of a rescue terminal with positioning, vital signs sensing, and communicating function for special environment. The terminal provides three-dimensional positioning functionality via China's Beidou 1 Navigation Satellite (BD1) System and can collect users' vital signs with a set of wireless sensors. A controller of the terminal is in charge of processing data collected from the wireless sensors and communicating with the monitoring platform. With features such as small sizing, low power consumption, and accurate positioning, this terminal is very helpful in special circumstances such as disaster relief, dangerous outdoor sports and adventure monitoring, and antiterrorism activities.


Assuntos
Desenvolvimento de Programas , Tecnologia de Sensoriamento Remoto/métodos , Comunicações Via Satélite , Telemedicina/métodos , Sinais Vitais , Planejamento em Desastres , Sistemas de Comunicação no Hospital , Humanos , Avaliação de Programas e Projetos de Saúde , Socorro em Desastres , Tecnologia de Sensoriamento Remoto/instrumentação , Telemedicina/instrumentação , Terrorismo
14.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(11): 3060-3, 2011 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-22242517

RESUMO

Based on the spectral characteristic of the detonation temperature, the present paper presents a measurement system of transient multi-wavelength pyrometry with the theory of multi-wavelength thermometry. The FPGA was applied as the hardware developing platform and the high-speed linear CCD was utilized. Each module was controlled by FPGA to achieve the process of real-time data acquisition, storage and transmission. Using the multiple regression analysis method, the dynamic spectral waveforms were calculated. The two laser spectral lines, 630 and 532 nm, were used to calibrate the corresponding pixel sequence numbers and the No. 175 and No. 270 were confirmed. In this paper, the halide tungsten light was measured. The results show that the system can sample continuous spectrum signal at several different times; the CCD can stably work with 40 MHz clock and the frame scanning frequency can achieve 73 kHz.

16.
Telemed J E Health ; 16(5): 634-8, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20575733

RESUMO

Although China started to study and implement telemedicine much later than other advanced countries, telemedicine is developing very fast in this country. Research on telemedicine is also getting popular, and more and more teleconsultant systems are being carried out. For the purpose of assessing the development of telemedicine in China over these past 50 years, we conducted a study of three elements, namely (1) teleconsultations, (2) academic activities, and (3) education. We carried out our study from three perspectives: the teleconsultant, telemedicine academic activities, and telemedicine education. In this article, we also show our recent achievement in telemedicine based on the Regional Collaborative Medical Service.


Assuntos
Difusão de Inovações , Informática Médica , Telemedicina/organização & administração , China , Sistemas de Computação , Educação a Distância/organização & administração , Educação Médica/organização & administração , Previsões , Planejamento em Saúde/organização & administração , Humanos , Informática Médica/educação , Informática Médica/instrumentação , Informática Médica/organização & administração , Integração de Sistemas , Telemedicina/instrumentação
17.
Telemed J E Health ; 16(6): 746-50, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20583952

RESUMO

The objective of this study was to share the experience of building an information security system for a regional collaborative medical platform (RCMP) and discuss the lessons learned from practical projects. Safety measures are analyzed from the perspective of system engineering. We present the essential requirements, critical architectures, and policies for system security of regional collaborative medical platforms.


Assuntos
Redes de Comunicação de Computadores/organização & administração , Simulação por Computador/normas , Comportamento Cooperativo , Sistemas de Informação Hospitalar/organização & administração , Sistemas Computadorizados de Registros Médicos/organização & administração , Regionalização/organização & administração , China , Redes de Comunicação de Computadores/normas , Segurança Computacional/normas , Computadores , Geografia , Política de Saúde , Sistemas de Informação Hospitalar/normas , Humanos , Fatores de Risco
18.
Telemed J E Health ; 16(3): 344-9, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20406121

RESUMO

China started to pay more attention to the construction of a regional and national health information network after the outbreak of the severe acute respiratory syndrome (SARS) epidemic in 2003. The construction of a public health system is considered the most important part of national medical reform, with information and computer technology serving as the key to deploying regional collaborative medical service, also known as e-health. In this paper, we analyze the difficulties in carrying out e-health projects in China, a discussion of ongoing projects, and a case presentation representing current progress.


Assuntos
Redes de Comunicação de Computadores/organização & administração , Informática Médica/organização & administração , Regionalização/organização & administração , Programas Médicos Regionais , China/epidemiologia , Humanos , Registro Médico Coordenado , Administração em Saúde Pública , Síndrome Respiratória Aguda Grave/epidemiologia
19.
Telemed J E Health ; 16(3): 364-9, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20406124

RESUMO

Data sharing and information exchange among medical institutions is a requirement for convenient and effective data availability for both healthcare professionals and patients. In this paper, the characteristics of medical data are studied; two mainstream technologies of data storage for medical information are compared, and three strategies of medical documents storage are described with detailed advantages and disadvantages. Semi-structured storage technology is easier to deploy and much more promising to promote in a wider range than all-structured methods. The combination of central and distributed data storage is more practical for regional data sharing. This analysis suggests that semi-structural data storage technology and the combination of central and distributed data storage are efficient and fit well the current situation in China.


Assuntos
Armazenamento e Recuperação da Informação/métodos , Internet , Sistemas Computadorizados de Registros Médicos/organização & administração , Desenvolvimento de Programas , China , Humanos , Disseminação de Informação
20.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 27(6): 1346-9, 2010 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-21374992

RESUMO

In this paper, the theory of complex adaptive system (CAS) and its modeling method are introduced. The complex characters of the hospital system is analyzed. The agile manufacturing and cell reconstruction technologies are used to reconstruct the hospital system. Then we set forth a research for simulation of hospital system based on the methodology of Multi-Agent technology and high level architecture (HLA). Finally, a simulation framework based on HLA for hospital system is presented.


Assuntos
Simulação por Computador , Sistemas de Informação Hospitalar , Humanos , Modelos Organizacionais
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