Interleukin-6, but not soluble adhesion molecules, predicts a subsequent mortality from cardiovascular disease in patients with acute ST-segment elevation myocardial infarction

Inflammatory responses are an important element in the atherosclerotic process. Therefore, inflammatory markers can potentially serve as predictors of cardiovascular risk. However, the existing data are limited and controversial. We conducted a prospective cohort study with 263 patients with first acute ST-segment elevation myocardial infarction (STEMI) who were admitted to our Hospital within 6 h after the symptoms onset. Clinical data were recorded and serum admission levels of interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble P-selectin (sP-selectin) were determined. The patients were then followed up for 3 years to document cardiovascular mortality. During the follow-up, 34 patients died from cardiovascular causes. The admission levels of IL-6 were significantly higher in these patients, whereas sICAM-1, sVCAM-1, and sP-selectin were comparable between these and the survived patients. The Kaplan–Meier plots revealed a significant increase in cardiovascular mortality with increasing levels of IL-6 (P = 0.0002, χ² test). The logistic regression analysis indicated that IL-6 was an independent predictor for cardiovascular mortality. To conclude, our findings indicate that elevated admission levels of IL-6, but not soluble adhesion molecules, provide valuable information for risk assessment of long-term cardiovascular mortality in patients with STEMI.     

泰山沙参属植物资源调查与营养成分分析

目的:了解泰山沙参属植物资源现状,测定其根中脂肪、蛋白质及多糖的含量,为合理开发利用泰山沙参属植物资源提供依据。方法:采用野外实地调查法进行资源考察;分别用索氏提取法、考马斯亮蓝法和苯酚-硫酸法测定脂肪、蛋白质和多糖的含量。结果:采集的100余份标本,经鉴定为沙参属植物狭叶沙参[Adenophora gmeli-nii(Spreng)Fisch.]、石沙参(Adenophora polyantha Nakai)、杏叶沙参(Adenophora stricta Mig.)及细叶沙参(Adeno-phora paniculata Nannf.)。泰山沙参属植物狭叶沙参、石沙参、杏叶沙参和细叶沙参脂肪含量分别为2.14%～7.34%,4.27%～7.72%1,.54%～2.51%和4.98%。蛋白质含量分别为0.60～2.10 mg/g0,.80～1.89 mg/g,0.83～0.89 mg/g和1.05 mg/g,多糖含量分别为20.58%～63.21%2,7.74%～65.14%,43.14%～48.47%和45.60%。结论:泰山野生沙参属植物资源丰富,品种多、分布广、蕴藏量大,多糖含量较高,具有较大的开发前景。     

Oestrogen regulates the expression of cathepsin E-A-like gene through ER$$\upbeta $$ in liver of chicken ( Gallus gallus)

The cathepsin E-A-like, also known as ‘similar to nothepsin’, is a new member of the aspartic protease family, which may take part in processing of egg yolk macromolecules, due to it was identified in the chicken egg-yolk. Previously, studies have suggested that the expression of cathepsin E-A-like increased gradually during sexual maturation of pullets, but the exact regulation mechanism is poorly understood. In this study, to gain insight into the function and regulation mechanism of the gene in egg-laying hen, we cloned the cathepsin E-A-like gene and evaluated its evolutionary origin by using both phylogenetic and syntenic methods. The mode of the gene expression regulation was analysed through stimulating juvenile hens with \(17\upbeta \)-estradiol and chicken embryo hepatocytes with \(17\upbeta \)-estradiol combined with oestrogen receptor antagonists including MPP, ICI 182,780 and tamoxifen. Our results showed that cathepsin E-A-like was an orthologoues gene with nothepsin, which is present in birds but not in mammals. The expression of cathepsin E-A-like significantly increased in a dose-dependent manner after the juvenile hens were treated with \(17\upbeta \)-estradiol (\(P~<~0.05\)). Compared with the \(17\upbeta \)-estradiol treatment group, the expression of cathepsin E-A-like was not significantly changed when the hepatocytes were treated with \(17\upbeta \)-estradiol combined with MPP (\(P~<~0.05\)). In contrast, compared with the \(17\upbeta \)-estradiol combined with MPP treatment group, the expression of cathepsin E-A-like was significantly downregulated when the hepatocytes were treated with \(17\upbeta \)-estradiol combined with tamoxifen or ICI 182,780 (\(P~<~0.05\)). These results demonstrated that cathepsin E-A-like shared the same evolutionary origin with nothepsin. The expression of cathepsin E-A-like was regulated by oestrogen, and the regulative effect was predominantly mediated through ER-\(\upbeta \) in liver of chicken.     

New Lithium Salt Forms Interphases Suppressing Both Li Dendrite and Polysulfide Shuttling

Lithium–sulfur batteries (LSBs) are considered promising candidates for the next‐generation energy‐storage systems due to their high theoretical capacity and prevalent abundance of sulfur. Their reversible operation, however, encounters challenges from both the anode, where dendritic and dead Li‐metal form, and the cathode, where polysulfides dissolve and become parasitic shuttles. Both issues arise from the imperfection of interphases between electrolyte and electrode. Herein, a new lithium salt based on an imide anion with fluorination and unsaturation in its structure is reported, whose interphasial chemistries resolve these issues simultaneously. Lithium 1, 1, 2, 2, 3, 3‐hexafluoropropane‐1, 3‐disulfonimide (LiHFDF) forms highly fluorinated interphases at both anode and cathode surfaces, which effectively suppress formation of Li‐dendrites and dissolution/shuttling of polysulfides, and significantly improves the electrochemical reversibility of LSBs. In a broader context, this new Li salt offers a new perspective for diversified beyond Li‐ion chemistries that rely on a Li‐metal anode and active cathode materials.     

一种宏观基因调控分子SATB1

自身多聚化的SATB1(special AT-rich sequences binding protein 1)围绕异染色质形成笼状结构分布在细胞核中,SATB1不仅结合染色质DNA的核基质结合区(matrix attachment regions,MARs),也结合核基质,能够使DNA锚定在核基质并形成袢环状结构(loop)。SATB1的磷酸化、乙酰化和小泛素化样修饰可调节其DNA结合能力和细胞核内亚结构的定位;SATB1与多种蛋白质相互作用,能够募集染色质重塑复合物和组蛋白修饰酶,实现对其靶基因表达的时空特异性调控。SATB1在调节细胞分化、细胞凋亡、肿瘤生长与转移和X染色体失活等方面起到重要作用,并有可能成为肿瘤转移的治疗靶点。     

A class of novel Schiff’s bases: Synthesis,therapeutic action for chronic pain,anti-inflammation and 3D QSAR analysis

To discover analgesics for treating chronic pain 17 novel Schiff’s bases, N,N′-(Z-allylidene-1,3-diyl)bisamino acid methyl esters were prepared from 1,1,3,3,-tetramethoxypropane and amino acid methyl esters. On tail-flick mouse model 20 μmol/kg of these Schiff’s bases were orally administered, the analgesic action started 30 min after administration, reached the maximum 120 min after administration, and at 180 min this action was still observed. On a xylene-induced ear edema mouse model 20 μmol/kg of these Schiff’s bases exhibited desirable anti-inflammation. Thus the present Schiff’s bases are able to treat chronic pain from inflammation. The effect of the side chains of the amino acid residues of these Schiff’s bases on the analgesic activity was explained with 3D QSAR.     

Conformational stability of CopC and roles of residues Tyr79 and Trp83

CopC is a periplasmic copper Chaperone protein that has a β‐barrel fold and two metal‐binding sites distinct for Cu(II) and Cu(I). In the article, four mutants (Y79F, Y79W, Y79WW83L, Y79WW83F) were obtained by site‐directed mutagenesis. The far‐UV CD spectra of the proteins were similar, suggesting that mutations did not bring any significant changes in secondary structures. Meanwhile the effects of mutations on the protein's function were manifested by Cu(II) binding. Fluorescence lifetime measurement and quenching of tryptophan fluorescence by acrylamide and KI showed that the microenvironment around Trp83 was more hydrophobic than that around Tyr79 in apoCopC. Unfolding experiments induced by guanidinium chloride (GdnHCl), urea provided the conformational stability of each protein. The Δ<ΔG⁰_element> obtained using the model of structural elements was used to show the role of Tyr79 and Trp83. On the one hand, the <ΔG⁰_element> induced by urea for Y79F, Y79W have a loss of 6.51, 2.03 kJ/mol, respectively, compared with apoCopC, proving that replacement of Tyr79 by Phe or Trp all decreased the protein stability, meaning that the hydrogen bonds interactions between Tyr79 and Thr75 played an important role in stabilizing apoCopC. On the other hand, the <ΔG⁰_element> induced by urea for Y79WW83L have a loss of 11.44 kJ/mol, but for Y79WW83F did a raise of 1.82 kJ/mol compared with Y79W. The replacement of Trp83 by Phe and Leu yields opposite effects on protein stability, which suggested that the aromatic ring of Trp83 was important in maintaining the hydrophobic core of apoCopC.     

Development of a new bioprocess scheme using frozen seed train intermediates to initiate CHO cell culture manufacturing campaigns

Agility to schedule and execute cell culture manufacturing campaigns quickly in a multi‐product facility will play a key role in meeting the growing demand for therapeutic proteins. In an effort to shorten campaign timelines, maximize plant flexibility and resource utilization, we investigated the initiation of cell culture manufacturing campaigns using CHO cells cryopreserved in large volume bags in place of the seed train process flows that are conventionally used in cell culture manufacturing. This approach, termed FASTEC (Frozen Accelerated Seed Train for Execution of a Campaign), involves cultivating cells to high density in a perfusion bioreactor, and cryopreserving cells in multiple disposable bags. Each run for a manufacturing campaign would then come from a thaw of one or more of these cryopreserved bags. This article reviews the development and optimization of individual steps of the FASTEC bioprocess scheme: scaling up cells to greater than 70 × 10⁶ cells/mL and freezing in bags with an optimized controlled rate freezing protocol and using a customized rack configuration. Flow cytometry analysis was also employed to understand the recovery of CHO cells following cryopreservation. Extensive development data were gathered to ensure that the quantity and quality of the drug manufactured using the FASTEC bioprocess scheme was acceptable compared to the conventional seed train process flow. The result of offering comparable manufacturing options offers flexibility to the cell culture manufacturing network. Biotechnol. Bioeng. 2013; 110: 1376–1385. © 2012 Wiley Periodicals, Inc.