Activated protein C--an anticoagulant that does more than stop clots

Activated protein C (APC) is a glycoprotein derived from its precursor, protein C and formed by the cleavage of an activation peptide by thrombin bound to thrombomodulin. Originally thought to be synthesized exclusively by the liver, recent reports have shown that protein C is synthesized by endothelial cells, keratinocytes and some hematopoietic cells.APC functions as a physiological anticoagulant with cytoprotective, anti-inflammatory and anti-apoptotic properties. In vitro and preclinical data have revealed that APC exerts its protective effects via an intriguing mechanism requiring endothelial protein C receptor and the thrombin receptor, protease-activated receptor-1. Remarkably, even though APC cleaves this receptor in an identical fashion to thrombin, it exerts opposing effects.Recently approved as a therapeutic agent for severe sepsis, APC is now emerging as a potential treatment for a number of autoimmune and inflammatory diseases including lung disorders, spinal cord injury and chronic wounds. The future pharmacologic use of APC holds remarkable promise.     

Rad9 plays an important role in DNA mismatch repair through physical interaction with MLH1

Rad9 is conserved from yeast to humans and plays roles in DNA repair (homologous recombination repair, and base-pair excision repair) and cell cycle checkpoint controls. It has not previously been reported whether Rad9 is involved in DNA mismatch repair (MMR). In this study, we have demonstrated that both human and mouse Rad9 interacts physically with the MMR protein MLH1. Disruption of the interaction by a single-point mutation in Rad9 leads to significantly reduced MMR activity. This disruption does not affect S/M checkpoint control and the first round of G₂/M checkpoint control, nor does it alter cell sensitivity to UV light, gamma rays or hydroxyurea. Our data indicate that Rad9 is an important factor in MMR and carries out its MMR function specifically through interaction with MLH1.     

Synthesis and antiviral activity of novel pyrazole derivatives containing oxime esters group

Fourteen title compounds, 1-substituted-5-substitutedphenylthio-4-pyrazolaldoxime ester derivatives 4a-4n, were synthesized from the starting material 1-substitutedphenyl-3-methyl-5-substitutedphenylthio-4-pyrazolaldoximes 3 by treatment with acyl chloride. The synthesized compounds were characterized by physical constants, and the structures of the title compounds were further confirmed by IR, 1H NMR, 13C NMR and elemental analysis. The bioassay results showed that title compounds possessed weak to good anti-TMV bioactivity with 4l showing significant enhancement of disease resistance in tobacco leaves with high affinity for TMV CP.     

P2X7 receptor inhibition attenuated sympathetic nerve sprouting after myocardial infarction via the NLRP3/IL‐1β pathway

Mounting evidence supports the hypothesis that inflammation modulates sympathetic sprouting after myocardial infarction (MI). The myeloid P2X₇ signal has been shown to activate the nucleotide‐binding and oligomerization domain‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome, a master regulator of inflammation. We investigated whether P2X₇ signal participated in the pathogenesis of sympathetic reinnervation after MI, and whether NLRP3/interleukin‐1β (IL‐1β) axis is involved in the process. We explored the relationship between P2X₇ receptor (P2X₇R) and IL‐1β in the heart tissue of lipopolysaccharide (LPS)‐primed naive rats. 3′‐O‐(4‐benzoyl) benzoyl adenosine 5′‐triphosphate (BzATP), a P2X₇R agonist, induced caspase‐1 activation and mature IL‐1β release, which was further neutralized by a NLRP3 inhibitor (16673‐34‐0). MI was induced by coronary artery ligation. Following infarction, a marked increase in P2X₇R was localized within infiltrated macrophages and observed in parallel with an up‐regulation of NLRP3 inflammasome levels and the release of IL‐1β in the left ventricle. The administration of A‐740003 (a P2X₇R antagonist) significantly prevented the NLRP3/IL‐1β increase. A‐740003 and/or Anakinra (an IL‐1 receptor antagonist) significantly reduced macrophage infiltration as well as macrophage‐based IL‐1β and NGF (nerve growth factor) production and eventually blunted sympathetic hyperinnervation, as assessed by the immunofluorescence of tyrosine hydroxylase (TH) and growth‐associated protein 43 (GAP 43). Moreover, the use of Anakinra partly attenuated sympathetic sprouting. This indicated that the effect of P2X₇ on neural remodelling was mediated at least partially by IL‐1β. The arrhythmia score of programmed electric stimulation was in accordance with the degree of sympathetic hyperinnervation. In vitro studies showed that BzATP up‐regulated secretion of nerve growth factor (NGF) in M1 macrophages via IL‐1β. Together, these data indicate that P2X₇R contributes to neural and cardiac remodelling, at least partly mediated by NLRP3/IL‐1β axis. Therapeutic interventions targeting P2X₇ signal may be a novel approach to ameliorate arrhythmia following MI.     

广东地区三种木本植物抗大气污染能力的比较

研究了工业污染区(佛山市小塘镇五星WX)和相对清洁区(广州华南植物园BG)生长的3种木本植物光叶山矾(Symplocos lancifolia)、银柴(Aporosa chinensis)和窿缘桉(Eucalyptus exserta)叶片对酸碱缓冲能力的差别。工业污染区3种植物的细胞液pH均比相对清洁区的低,光叶山矾与银柴对酸和碱的缓冲能力强于窿缘桉。用外源NaHSO3处理,植物叶片的光合放氧、Fv／Fm、Fv／Fo和ФPsⅡ都有不同程度的下降。其中,窿缘桉下降的幅度最大,说明其抗大气污染的能力不如光叶山矾和银柴,同时也证明了用缓冲能力作为一种评价植物抗污能力的指标具有一定的科学性。     

Enhanced aerobic granulation and nitrogen removal by the addition of zeolite powder in a sequencing batch reactor

The aim of this study was to evaluate the impact of zeolite powders on feasibility of rapid aerobic granulation in the column-type sequencing batch reactors. After 90 days' operation, aerobic granular sludge was formed in both reactors by altering influent chemical oxygen demand/nitrogen (COD/N) ratios. R1 with zeolite powders had better removal capabilities of COD and total nitrogen than R2, which was without zeolite powders. Mixed liquor volatile suspended solid concentrations of the two reactors were 7.36 and 5.45 g/L, while sludge volume index (SVI₃₀) values were 34.9 and 47.9 mg/L, respectively. The mean diameters of aerobic granular sludge in the above two reactors were 2.5 and 1.5 mm, respectively. Both reactors achieved the largest simultaneous nitrification and denitrification (SND) efficiency at an influent COD/N ratio of 8; however, R1 exhibited more excellent SND efficiency than R2. The obtained results could provide a novel technique for rapid aerobic granulation and N removal simultaneously, especially when treating nitrogen-rich industrial wastewater.     

Increase of anti-HIV activity of C-peptide fusion inhibitors using a bivalent drug design approach

We reported the design of fusion inhibitors with improved activity using a multivalent inhibitor design strategy. First, we chose C29 as the template sequence, which is a 29-mer peptide derived from HIV-1 gp41 CHR domain and has anti-HIV activity of IC₅₀ 118 nM in a cell–cell fusion assay. We optimized the crosslink sites and linkers of the template peptide. We found that N-terminal crosslink caused activity improvement based on the multivalent co-operative effect. Especially, the IC₅₀ of peptide (CAcaC29)₂ was improved from 49.02 (monomeric form) to 5.71 nM. Compared with long peptides, short peptides may be more suitable to analyze the co-operative effect. So we selected a shorter peptide C22 to synthesize the bivalent inhibitors. Due its weak helicity, no co-operative effect appeared. Therefore, we chose SC22EK, which were introduced salt bridges to consolidate the helicity based on the natural sequence C22. The cross-linked (CAcaSC22EK)₂ was four times more potent than the monomer SC22EK in anti-HIV activity, with an IC₅₀ value of 4.92 nM close to the high active peptide fusion inhibitor C34. The strategy used in this study may be used to design new fusion inhibitors to interfere similar processes.     

祁连山地区植被特征及其分布规律

分析和讨论了祁连山地区主要植被类型及其分布特征。祁连山地区随着青藏高原的强烈隆升表现为整体抬升,植被具有明显的生态地理边缘效应特征和高原地带性规律。该区植被虽然受到四周的较大影响,但各类高寒植被占有绝对优势,表现出与青藏高原植被整体明显的相似性和广泛的一致性。另一方面,本区植被也有其特殊性及与高原面存在一些差异。因此,建议把祁连山地区做为青藏高原植被区的次一级独立单元     

Cytotoxic,clonal fidelity,and antioxidant evaluation of in vitro propagated Vitex negundo var. cannabifolia

Plant Cell, Tissue and Organ Culture (PCTOC) - Vitex negundo L. var. cannabifolia (Sieb. et Zucc.) Hand.-Mazz. is an important medicinal plant rich in bioactive compounds. In vitro tissue culture...