CytoSVM: an advanced server for identification of cytokine-receptor interactions

The interactions between cytokines and their complementary receptors are the gateways to properly understand a large variety of cytokine-specific cellular activities such as immunological responses and cell differentiation. To discover novel cytokine-receptor interactions, an advanced support vector machines (SVMs) model, CytoSVM, was constructed in this study. This model was iteratively trained using 449 mammal (except rat) cytokine-receptor interactions and about 1 million virtually generated positive and negative vectors in an enriched way. Final independent evaluation by rat's data received sensitivity of 97.4%, specificity of 99.2% and the Matthews correlation coefficient (MCC) of 0.89. This performance is better than normal SVM-based models. Upon this well-optimized model, a web-based server was created to accept primary protein sequence and present its probabilities to interact with one or several cytokines. Moreover, this model was applied to identify putative cytokine-receptor pairs in the whole genomes of human and mouse. Excluding currently known cytokine-receptor interactions, total 1609 novel cytokine-receptor pairs were discovered from human genome with probability ∼80% after further transmembrane analysis. These cover 220 novel receptors (excluding their isoforms) for 126 human cytokines. The screening results have been deposited in a database. Both the server and the database can be freely accessed at http://bioinf.xmu.edu.cn/software/cytosvm/cytosvm.php

Effectiveness of erythropoietin supplementation against chronic heart failure with anemia, and its effect on serum hypersensitive C reaction protein, homocysteic acid and Btype natriuretic peptide

Purpose: To study the effectiveness of exogenous erythropoietin (EPO) against chronic heart failure (CHF) with anemia, and its effect on serum hypersensitive C reaction protein (hs-CRP), homocysteic acid (Hcy ) and B-type natriuretic peptide (BNP).Methods: A total of 136 patients suffering from CHF with anemia from June 2015 to June 2017 were randomly divided into observation group (n = 68) and control group (n = 68). On the basis of conventional anti-heart failure therapy, the control group received oral ferrous sulfate tablets, while the observation group received oral ferrous sulfate tablets combined with EPO subcutaneous injection. Blood indices, cardiac function and serology were determined and tested in all patients before treatment, and at 4 months after treatment.Results: After treatment, hemoglobin (Hb), hematocrit (HCT), red blood cell (RBC), blood platelet count (PLT) and serum iron were significantly higher than those before treatment in the two groups; the levels in the observation group were significantly higher than those in control group (p <0.05). Following treatment, left ventricular ejection fraction (LVEF), and 6-minute walking distance in the observation group were significantly higher than those in the control group, while end-diastolic dimension (LVEDD), end-systolic dimension (LVESD) and cardiac functional grading in the observation group were significantly lower than those in the control group (p < 0.05). After treatment, hs-CRP, Hcy and BNP were significantly lower than pre-treatment values in the two groups, while the values for the observation group were significantly lower than those of control group (p <0.05). Correlation analysis showed that LVEF and Hb were negatively correlated with hs-CRP, Hcy and BNP (p <0.05).Conclusion: Serum hs-CRP, Hcy and BNP are involved in the occurrence and progression of CHF with anemia. Exogenous EPO can effectively improve anemia and cardiac function in these patients.Keywords: Erythropoietin, Chronic heart failure, Anemia, C-reaction protein, B-type natriuretic peptid

trans-4-(1-Naphth­yl)-2-oxo-1,3-oxazolidine-5-carboxylic acid

The crystal structure of the title compound, C14H11NO4, is influenced by N—H⋯O and O—H⋯O hydrogen bonds, linking mol­ecules into one-dimensional tapes running along the [010] direction

GRB 200829A: External Shock Origin of the Very Early Prompt Emission?

Long-duration GRB~200829A was detected by Fermi-GBM and Swift-BAT/XRT, and then rapidly observed by other ground-based telescopes. It has a weak $\gamma$-ray emission in the very early phase and followed by a bright spiky $\gamma$-ray emission pulse. The radiation spectrum of the very early emission is best fitted by a power-law function with index $\sim -1.7$. However, the bright spiky $\gamma$-ray pulse, especially the time around the peak, exhibits a distinct two-component radiation spectra, i.e., Band function combined with a blackbody radiation spectrum. We infer the photospheric properties and reveal a medium magnetization at photospheric position by adopting the initial size of the outflow as $r_0=10^9$~cm. It implies that Band component in this pulse may be formed during the dissipation of magnetic field. The power-law radiation spectra found in the very early prompt emission may imply the external-shock origination of this phase. Then, we perform Markov Chain Monte Carlo method fitting on the light-curves of this burst, where the jet corresponding to the $\gamma$-ray pulses at around $20$~s is used to refresh the external-shock. It is shown that the light-curves of very early phase and X-ray afterglow after $40$~s, involving the X-ray bump at around $100$~s, can be well modelled in the external-shock scenario. For the obtained initial outflow, we estimate the minimum magnetization factor of the jet based on the fact that the photospheric emission of this jet is missed in the very early phase.Comment: Accepted for publication in Astrophysical Journa

Kerr-Sen Black Hole as Accelerator for Spinning Particles

It has been proved that arbitrarily high-energy collision between two particles can occur near the horizon of an extremal Kerr black hole as long as the energy $E$ and angular momentum $L$ of one particle satisfies a critical relation, which is called the BSW mechanism. Previous researchers mainly concentrate on geodesic motion of particles. In this paper, we will take spinning particle which won't move along a timelike geodesic into our consideration, hence, another parameter $s$ describing the particle's spin angular momentum was introduced. By employing the Mathisson-Papapetrou-Dixon equation describing the movement of spinning particle, we will explore whether a Kerr-Sen black hole which is slightly different from Kerr black hole can be used to accelerate a spinning particle to arbitrarily high energy. We found that when one of the two colliding particles satisfies a critical relation between the energy $E$ and the total angular momentum $J$, or has a critical spinning angular momentum $s_c$, a divergence of the center-of-mass energy $E_{cm}$ will be obtained.Comment: Latex,17 pages,1 figure,minor revision,accepted by PR

N-[3-Chloro-4-(3-fluoro­benz­yloxy)phen­yl]-6-iodo­quinazolin-4-amine

In the title mol­ecule, C21H14ClFIN3O, the bicyclic ring system has a twisted conformation; the two fused rings form a dihedral angle of 4.5 (1)°. The dihedral angles between the fused ring system and the benzene rings are 27.3 (6) and 5.3 (5)° while the dihedral angle between the benzene rings is 22.0 (5)°. In the crystal structure, weak inter­molecular N—H⋯N hydrogen bonds link the mol­ecules into chains propagating in [100]. A short inter­molecular distance of 3.806 (3) Å between the centroids of the fluorobenzene and iodobenzene rings suggests the existence of π–π stacking inter­actions

In vitro drug release behavior from a novel thermosensitive composite hydrogel based on Pluronic f127 and poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) copolymer

<p>Abstract</p> <p>Background</p> <p>Most conventional methods for delivering chemotherapeutic agents fail to achieve therapeutic concentrations of drugs, despite reaching toxic systemic levels. Novel controlled drug delivery systems are designed to deliver drugs at predetermined rates for predefined periods at the target organ and overcome the shortcomings of conventional drug formulations therefore could diminish the side effects and improve the life quality of the patients. Thus, a suitable controlled drug delivery system is extremely important for chemotherapy.</p> <p>Results</p> <p>A novel biodegradable thermosensitive composite hydrogel, based on poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) and Pluronic F127 copolymer, was successfully prepared in this work, which underwent thermosensitive sol-gel-sol transition. And it was flowing sol at ambient temperature but became non-flowing gel at body temperature. By varying the composition, sol-gel-sol transition and <it>in vitro </it>drug release behavior of the composite hydrogel could be adjusted. Cytotoxicity of the composite hydrogel was conducted by cell viability assay using human HEK293 cells. The 293 cell viability of composite hydrogel copolymers were yet higher than 71.4%, even when the input copolymers were 500 μg per well. Vitamin B₁₂(VB₁₂), honokiol (HK), and bovine serum albumin (BSA) were used as model drugs to investigate the <it>in vitro </it>release behavior of hydrophilic small molecular drug, hydrophobic small molecular drug, and protein drug from the composite hydrogel respectively. All the above-mentioned drugs in this work could be released slowly from composite hydrogel in an extended period. Chemical composition of composite hydrogel, initial drug loading, and hydrogel concentration substantially affected the drug release behavior. The higher Pluronic F127 content, lower initial drug loading amount, or lower hydrogel concentration resulted in higher cumulative release rate.</p> <p>Conclusion</p> <p>The results showed that composite hydrogel prepared in this paper were biocompatible with low cell cytotoxicity, and the drugs in this work could be released slowly from composite hydrogel in an extended period, which suggested that the composite hydrogel might have great potential applications in biomedical fields.</p

Molecular characterization of the envelope gene of dengue virus type 3 newly isolated in Guangzhou, China, during 2009–2010

SummaryBackgroundAfter an absence of 29 years, dengue virus type 3 (DENV-3) re-emerged in Guangzhou in 2009 and again in 2010. However, the geographical route by which the virus entered the city, and how it has changed genetically, remain unclear. Therefore, we carried out a comprehensive investigation into the molecular characteristics of the DENV-3 involved.MethodsThe envelope (E) genes of viruses isolated from dengue patients during the 2009–2010 epidemics were sequenced and compared with previously published E gene sequences of global representative DENV-3 strains available in GenBank, including isolates circulating in other provinces of China.ResultsA total of 13 isolates (seven from 2009 and six from 2010) were obtained from human serum samples. Phylogenetic analysis revealed that the isolates were grouped into three genotypes (I, III, and V) and then two clades within genotype III (genotype I from Indonesia, genotype III clade A from Côte d’Ivoire, genotype III clade B from Tanzania, and genotype V from Philippines). In addition, there were 1.3–9.0% and 0.5–3.9% differences in the nucleic and deduced amino acid sequences between the 2009 and 2010 strains, respectively.ConclusionsThe DENV-3 viruses from the period 2009–2010 were not from the continuous spread of an epidemic strain or the re-emergence of the 2009 strains in the 2-year period. The introduction of different DENV-3 genotypes following more than one geographical route was an important contributing factor to the 2009–2010 dengue epidemics in Guangzhou