国家及省级疾病预防控制机构学术影响力分析研究

运用h指数、ESI高被引论文、ESI热点论文等文献计量学指标分析Web of Science^TM上2007-2016年间中国疾病预防控制中心及省级疾病预防控制中心的论文,对比中国疾病预防控制中心、5个SCI论文量最多的省级疾病预防控制中心的学术影响力,提出发挥中国疾病预防控制中心的学术带头作用、各省级疾病预防控制中心在各自研究领域继续发挥所长等建议。     

科技论文评价指标相关性比较分析

目的：以F1000文献为基础,对比分析SCIE被引频次、ESI高被引、FS、Altmetrics各项指标（Altmetrics Score,Twitter,Mendeley）之间的关系,探讨不同论文评价指标相关性。方法：筛选数据引入各个指标获得2个样本集,运用斯皮尔曼相关性比较方法探讨各项指标的相关关系。结果：样本1中,被引频次与各指标相关系数最高为0.836,最低为0.416,ESI高被引与各指标相关系数在0.6左右波动,Altmetrics Score与Twitter、Mendeley相关系数分别为0.796和0.714。样本2中,被引频次与各指标相关系数最高为0.945,FS与Altmetrics各指标相关系数在0.528-0.745之间,Altmetrics Score与Twitter相关系数达0.873。结论：被引频次和ESI高被引、Altmetrics Score、Twitter、Mendeley呈正相关,FS与被引频次、ESI高被引无相关性,与Altmetrics各指标和Mendeley指标呈正相关。Altmetrics Score与Twitter、Mendeley呈正相关。     

Effects of Excipients on Protein Conformation in Lyophilized Solids by Hydrogen/Deuterium Exchange Mass Spectrometry

Purpose Excipients are added to lyophilized protein drug formulations to protect the protein during processing and storage, but the mechanisms are poorly understood. Here, hydrogen/deuterium (H/D) exchange with mass spectrometry was used to assess protein conformation and excipient interactions in lyophilized solids. Methods Calmodulin (CaM, 17 kD) was co-lyophilized with carbohydrate excipients (sucrose, mannitol, trehalose, raffinose, dextran 5,000, dextran 12,000) or guanidine hydrochloride (negative control) and exposed to D₂O vapor at 33% RH and RT. Samples were then dissolved and analyzed by mass spectrometry (+ESI/MS). Peptic digestion provided additional, site-specific information on H/D exchange. Solids were further characterized by powder x-ray diffraction (PXRD), differential scanning calorimetry (DSC), infrared spectroscopy (FTIR) and water vapor sorption. Results Excipients protected CaM from H/D exchange, increasing in the order guanidine hydrochloride < no excipient, mannitol < dextran 5,000, dextran 12,000 < sucrose < raffinose < trehalose. Effects were exerted primarily in the protein’s α-helical segments. Conclusions The effects of carbohydrate excipients on protein conformation in lyophilized solids are not exhibited uniformly along the protein sequence, but instead are exerted in a site-specific manner. The results also demonstrate the utility of H/D exchange with ESI/MS for protein structure characterization in lyophilized samples.     

基于ESI和InCites的高校学科竞争力分析

以ESI免疫学科为例，介绍中国医科大学图书馆如何基于ESI和InCites开展学科竞争力分析，提出了建立智慧化学科竞争力分析平台、开展多种学科分类体系下的情报分析、运用新媒体技术进行多元化资源推介和结合多维度指标进行学术资源评价等策略以提升高校的学科竞争力分析能力的策略。     

AKR1B10 induces cell resistance to daunorubicin and idarubicin by reducing C13 ketonic group

Daunorubicin, idarubicin, doxorubicin and epirubicin are anthracyclines widely used for the treatment of lymphoma, leukemia, and breast, lung, and liver cancers, but tumor resistance limits their clinical success. Aldo-keto reductase family 1 B10 (AKR1B10) is an NADPH-dependent enzyme overexpressed in liver and lung carcinomas. This study was aimed to determine the role of AKR1B10 in tumor resistance to anthracyclines. AKR1B10 activity toward anthracyclines was measured using recombinant protein. Cell resistance to anthracycline was determined by ectopic expression of AKR1B10 or inhibition by epalrestat. Results showed that AKR1B10 reduces C13-ketonic group on side chain of daunorubicin and idarubicin to hydroxyl forms. In vitro, AKR1B10 converted daunorubicin to daunorubicinol at V_max of 837.42 ± 81.39 nmol/mg/min, K_m of 9.317 ± 2.25 mM and k_cat/K_m of 3.24. AKR1B10 showed better catalytic efficiency toward idarubicin with V_max at 460.23 ± 28.12 nmol/mg/min, K_m at 0.461 ± 0.09 mM and k_cat/K_m at 35.94. AKR1B10 was less active toward doxorubicin and epirubicin with a C14-hydroxyl group. In living cells, AKR1B10 efficiently catalyzed reduction of daunorubicin (50 nM) and idarubicin (30 nM) to corresponding alcohols. Within 24 h, approximately 20 ± 2.7% of daunorubicin (1 μM) or 23 ± 2.3% of idarubicin (1 μM) was converted to daunorubicinol or idarubicinol in AKR1B10 expression cells compared to 7 ± 0.9% and 5 ± 1.5% in vector control. AKR1B10 expression led to cell resistance to daunorubicin and idarubicin, but inhibitor epalrestat showed a synergistic role with these agents. Together our data suggest that AKR1B10 participates in cellular metabolism of daunorubicin and idarubicin, resulting in drug resistance. These data are informative for the clinical use of idarubicin and daunorubicin.     

Saliva electrophoretic protein profiles in infants: changes with age and impact of teeth eruption and diet transition

Objective

The objective of this study was to describe the changes in salivary protein profiles in infants between the ages of 3 and 6 months, and to evaluate the impact of teeth eruption and introduction of solid foods on such profiles.

Design

73 infants were followed longitudinally at 3 and 6 months of age. Their whole saliva proteins were separated by SDS–PAGE electrophoresis and semi-quantified by image analysis. Amylase activity was also measured on a sub-sample of the population (n = 42 infants). Bands which abundance was significantly different between the two ages according to paired comparisons were identified by mass spectrometry techniques.

Results

Out of 21 bands, 13 were significantly different between 3 and 6 months of age. Two short variants of amylase increased in abundance with age, as did amylase activity. Other changes possibly translated developmental physiological events, for example maturation of the adaptive immune system. The balance between S-type cystatins and cystatins A and B was modified, in favour of S-type cystatins at 6 months of age. Teeth eruption resulted in an increase in albumin abundance, whilst introduction of solid foods was associated with higher levels of β-2 microglobulin and S-type cystatins.

Conclusions

Salivary profiles were modified substantially between the ages of 3 and 6 months. Both teeth eruption and diet had an impact on abundance changes for some proteins, revealing dynamic interactions between saliva proteome, oral physiology and diet.     

“Anatomical” View of the Protein Composition and Protein Characteristics for Gloydius shedaoensis Snake Venom via Proteomics Approach

The bioactive protein components from snake venom complexes have been utilized for studies of enzymology, structural biology, and pharmacology. The Gloydius shedaoensis snake (GSS) is the only snake species found exclusively at the Chinese Shedao (snake) Island in Dalian. To investigate the protein components of Chinese GSS venom (GSSV), we initialized a proteomic assay for GSSV by the combination of sodium dodecyl sulfate‐polyacrylamide gel electrophoresis with high‐performance liquid chromatography (HPLC)‐nanoelectrospray ionization tandem mass spectrometry (nESI‐MS/MS). Thirty gel bands visualized by Coomassie blue staining were excised and digested by trypsin. The tryptic‐digested peptides were separated by HPLC and subsequently sequenced by nESI‐MS/MS. Twenty‐four types of proteins were identified by searching the mass spectrometry data against NCBInr database through TurboSequest Bioworks. The most abundant proteins are phospholipase A₂, metalloproteinase, L ‐amino acid oxidase (LAAO), serine protease/thrombin‐like enzyme. Except for 20 types of known snake venom proteins, the homolog peptides of hypothetical protein PFLC2230, LOC495267 protein, DEAD/DEAH box helicase‐like, and pancreatic trypsin 1 from other organisms are matched for GSSV protein components. Mass spectrometric data also indicated that (i) dimerization happens to PLA₂s as monomer and dimer of PLA₂s coexist in GSSV and (ii) truncation or hydrolysis might happen to LAAOs as three molecular‐weight‐ranged LAAO species are present in GSSV. The results provide an “anatomical” view of the protein composition and important information for protein characteristics of GSSV. Anat Rec, 2011. © 2010 Wiley‐Liss, Inc.     

Immunomodulatory effects of crude phenylethanoid glycosides from Ligustrum purpurascens

Ethnopharmacological relevance

Ligustrum purpurascens, named as “Ku ding cha”, has been used as a kind of functional tea in southern China for about two thousand years, which has the effects on diuresis, anti-hypertension, weight-loss and anti-inflammation.

The aim of the study

This study was aimed to investigate the immune enhancement effects of the crude phenylethanoid glycosides (CPGs) from Ligustrum. Purpurascens on mice and analyze the chemical profiles of phenylethanoid glycosides in the CPGs.

Materials and methods

The immune functions enhancing potential of CPGs was determined using serum hemolysin antibody, phagocytosis, splenocyte antibody production, and NK cells activity assays. The contents of five major constituents in the crude glycosides of Ligustrum purpurascens were determined by using liquid chromatography, other five glycosides were deduced according to their UV and MS spectra compared with the literature as well.

Results

In the immunizing experiment, mice treated with different doses of CPGs showed an increase (p<0.01) in the haemagglutination titre compared with the control group. The increases (p<0.05) were found to be significant at doses of 440 mg/kg and 1.32 g/kg in the experiments of antibody production of spleen cells, MΦ phagocytosis of chicken RBCs and NK cell activity. Further chemical characterization yielded 10 constituents from CPGs, five glycosides were quantified by HPLC and the structures of other five compounds were speculated according to their UV and MS spectra.

Conclusion

The results suggested that phenylethanoid glycosides from Ligustrum purpurascens have immunomodulatory effects on mice.     

Biochemical characterizations of Escherichia coli-expressed protective antigen Ag473 of Neisseria meningitides group B

Polysaccharide-based vaccines against Neisseria meningitidis (Nm) serogroups A, C, Y and W135 have been available since 1970, but similar vaccine candidates developed for Nm group B (NmB) have not been successful due to both poor immunogenicity and their potential immunological cross-reactivity with human neurological tissue. In previous reports, a protective antigen and vaccine candidate, Ag473, was identified using proteomics and NmB-specific bactericidal monoclonal antibody. To initiate human phase one clinical trials, antigen production and characterization, pre-clinical toxicology and animal studies are required. In the present study, we report the biochemical characterization of Escherichia coli-expressed recombinant Ag473 (rAg473). Using MALDI-TOF mass analysis, chromatographically purified rAg473 was found to have two major isoforms that have molecular masses of 11,306 and 11,544amu, respectively. The isoforms were separated using RP-HPLC and pooled into two fractions. Based on the chromatogram, the ratio of lipoproteins in fractions #1 and #2 was found to be 1-2. GC-MS analysis of lipoproteins was performed, and the acylated fatty acids were identified. The results indicated that the first lipoproteins in fraction #1 contained the lipids palmitic acid (C16:0), cyclopropaneoctanoic acid (C17:1) and, predominately, stearic acid (C18:0). A different lipid composition of cyclopropaneoctanoic acid (C17:1), oleic acid (C18:1) and, predominately, palmitic acid (C16:0) was found in the second lipoprotein fraction. Both lipoprotein isoforms were tested and found to have Toll-like receptor (TLR) agonist activity in stimulating cytokine secretion from THP-1 cells. Circular dichroism (CD) analysis showed the secondary structure of rAg473 to be dominated by α-helices (48%), and the overall protein structure was stable up to 60°C and could refold after having been exposed to a temperature cycle from 20 to 90°C. In addition, the solubility of rAg473 (5mg/mL) was not affected after several freeze-thaw cycles. These biophysical and immunological properties make rAg473 a good vaccine candidate against NmB.     

Cytostatic inhibition of cancer cell growth by lignan secoisolariciresinol diglucoside

Our previous study demonstrated that lignan metabolites enterolactone and enterodiol inhibited colonic cancer cell growth by inducing cell cycle arrest and apoptosis. However, the dietary lignans are naturally present as glycoside precursors, such as secoisolariciresinol diglucoside (SDG), which have not been evaluated yet. This study tested the hypothesis that dietary SDG might have a different effect than its metabolites in human colonic SW480 cancer cells. Treatment with SDG at 0 to 40 μmol/L for up to 48 hours resulted in a dose- and time-dependent decrease in cell numbers, which was comparable to enterolactone. The inhibition of cell growth by SDG did not appear to be mediated by cytotoxicity, but by a cytostatic mechanism associated with an increase of cyclin A expression. Furthermore, high-performance liquid chromatography analysis indicated that SDG in the media was much more stable than enterolactone (95% of SDG survival vs 57% of enterolactone after 48-hour treatment). When the cells were treated with either enterolactone or SDG at 40 μmol/L for 48 hours, the intracellular levels of enterolactone, as measured by high-performance liquid chromatography–mass spectrometry/electron spray ionization, were about 8.3 × 10⁻⁸ nmol per cell; but intracellular SDG or potential metabolites were undetectable. Taken together, SDG demonstrated similar effects on cell growth, cytotoxicity, and cell cycle arrest when compared with its metabolite enterolactone. However, the reliable stability and undetectable intracellular SDG in treated cells may suggest that metabolism of SDG, if exposed directly to the colonic cells, could be different from the known degradation by microorganisms in human gut.