Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex.

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.

Author Correction: Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Rapid and Controllable Synthesis of Nanocrystallized Nickel-Cobalt Boride Electrode Materials via a Mircoimpinging Stream Reaction for High Performance Supercapacitors.

Nickel-cobalt borides (denoted as NCBs) have been considered as a promising candidate for aqueous supercapacitors due to their high capacitive performances. However, most reported NCBs are amorphous that results in slow electron transfer and even structure collapse during cycling. In this work, a nanocrystallized NCBs-based supercapacitor is successfully designed via a facile and practical microimpinging stream reactor (MISR) technique, composed of a nanocrystallized NCB core to facilitate the charge transfer, and a tightly contacted Ni-Co borates/metaborates (NCBi ) shell which is helpful for OH- adsorption. These merits endow NCB@NCBi a large specific capacity of 966 C g-1 (capacitance of 2415 F g-1 ) at 1 A g-1 and good rate capability (633.2 C g-1 at 30 A g-1 ), as well as a very high energy density of 74.3 Wh kg-1 in an asymmetric supercapacitor device. More interestingly, it is found that a gradual in situ conversion of core NCBs to nanocrystallized Ni-Co (oxy)-hydroxides inwardly takes place during the cycles, which continuously offers large specific capacity due to more electron transfer in the redox reaction processes. Meanwhile, the electron deficient state of boron in metal-borates shells can make it easier to accept electrons and thus promote ionic conduction.

Cryopreservation disrupts lipid rafts and heat shock proteins in yellow catfish sperm.

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.

[Nasal endoscopy-assisted bulboprostatic anastomosis for posterior urethral stricture].

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.

Application of x-ray energy dispersive spectroscopy to analyzing the thickness of diamond-like carbon film deposited on the surface of microparticles.

Depositing diamond-like carbon (DLC) film is considered to be more promising for surface modification of microparticles. The development of reliable and precise measurement techniques for DLC coatings on microparticles is crucial for advancing research in this field. This paper introduces a methodological approach for quantifying the thickness of the film on microparticles. The thickness of the film is obtained by establishing the quantitative relationship between the energy lost when electrons pass through the film and the thickness of the film. The proposed method allows for the estimation of film thickness by assessing solely the elemental abundance on the particle surfaces.

[Research on the method of transient spectrum detection based on array CCD].

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.

Wood-Derived, Vertically Aligned, and Densely Interconnected 3D SiC Frameworks for Anisotropically Highly Thermoconductive Polymer Composites.

Construction of a vertically aligned and densely interconnected ordered 3D filler framework in a polymer matrix is a challenge to attain significant thermal conductivity (TC) enhancement efficiency. Fortunately, many biomaterials with unique microstructures can be found in nature. With inspiration from wood, artificial composites can be rationally designed to achieve desired properties. Herein, the authors report a facile and effective approach to fabricate anisotropic polymer composites by biotemplate ceramization technology and subsequent vacuum impregnation of epoxy resin. The hierarchical microstructure of wood is perfectly replicated in the cellular biomass derived SiC (bioSiC) framework by carbothermal reduction. Owing to the anisotropic architecture of bioSiC, the epoxy composite with vertically aligned dense SiC microchannels shows interesting properties, including a high TC (10.27 W m-1 K-1 ), a significant enhancement efficiency (259 per 1 vol% loading), an outstanding anisotropic TC ratio (5.77), an extremely low coefficient of linear thermal expansion (12.23 ppm K-1 ), a high flexural strength (222 MPa), and an excellent flame resistance. These results demonstrate that this approach is expected to open a new avenue for design and preparation of high performance thermal management materials to address the heat dissipation of modern electronics.

The design and implementation of a rescue terminal with vital signs telemonitoring based on Beidou 1 navigation satellite system.

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.

E-health-oriented community health information system in china: our challenges, solution, and experience.

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.

[Real-time measurement of detonation transient temperature].

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.

Development and recent achievements of telemedicine in china.

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.

A study on an information security system of a regional collaborative medical platform.

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.

E-health in China: challenges, initial directions, and experience.

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.

A comparison of two data storage strategies for implementing e-health in China.

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.

[Research on multi-agent based modeling and simulation of hospital system].

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.

GC-Net: Global context network for medical image segmentation.

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.

Non-nucleoside inhibitors of HCV polymerase NS5B. Part 3: synthesis and optimization studies of benzothiazine-substituted tetramic acids.

Benzothiazine-substituted tetramic acids were discovered as highly potent non-nucleoside inhibitors of HCV NS5B polymerase. X-ray crystallography studies confirmed the binding mode of these inhibitors with HCV NS5B polymerase. Rational optimization of time dependent inactivation of CYP 3A4 and clearance was accomplished by incorporation of electron-withdrawing groups to the benzothiazine core.

[The computerized clinical practical guideline's research and implementation].

OBJECTIVE: To discuss the development module of ontology-based computerized clinical practical guideline, and to supply the technology support for implement of alerm/reminding, data sharing, evidence-based medicine and clinical decision making in the medical information system. METHODS: Analyse the structure and field ontology of the Guideline Interchange Format (GLIF); expand GLIF based on the Guideline of Cerebrovascular Disease Prevention and Treatment in China and Neurology Disease Ontology. RESULTS: A Chinese computerized guideline of intravenous thrombolytic therapy of acute cerebral infarction is constructed, which included metadata of edition description, list of drug data item, explanation of evidence strength, steps of indications decision, contraindication decision and drug selection. CONCLUSION: The computerized clinical practical guideline combined with clinical information system and Electronic Medical Records plays an important role in clinical pathways optimizing and decision making.

Manganese oxide doping carbon aerogels prepared with MnO2 coordinated by N, N - dimethylmethanamide for supercapacitors.

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.