PAQR3: a novel tumor suppressor gene

PAQR3, also known as RKTG (Raf kinase trapping to Golgi), is a member of the progestin and adipoQ receptor (PAQR) family. The role of PAQR3 as a tumor suppressor has recently been established in different types of human cancer in which PAQR3 exerts its biological function through negative regulation of the oncogenic Raf/MEK/ERK signaling. Multiple studies have found that PAQR3 downregulation frequently occurs in human cancers and is very often associated with tumor progression and shortened patients’ survival. Moreover, restoring the expression of PAQR3 could induce apoptosis and inhibit proliferation and invasiveness of cancer cells. Downregulation of PAQR3 by oncogenic microRNAs has also been reported. In this review, we summarized current knowledge concerning the role of PAQR3 in tumor development. To our knowledge, this is the first review on the role of this novel tumor suppressor.     

人胰腺α-淀粉酶的cDNA克隆和原核表达的初步研究

目的 获得人胰腺α-淀粉酶(AMY2A)基因并进行原核表达。方法 采用基因工程技术,根据人AMY2A基因序列设计并合成特异性引物;从人胰腺组织中提取总RNA,反转录成CDNA第一链;逆转录-聚合酶链反应(RT-PCR)扩增人胰腺AMY2A基因,经BamH Ⅰ和Kpn Ⅰ双酶切、连接并插入原核表达载体pGEX-5T,构建pGEX-5T-AMY2A重组表达载体,在大肠杆菌BL21中异丙基硫代半乳糖苷酶(IPTG)诱导表达AMY2A蛋白。包涵体经尿素变性、复性及谷胱苷肽琼脂糖柱亲和层析纯化、AMY2A酶活性测定和免疫印迹分析。结果 重组质粒测序和酶切结果显示AMY2A基因已正确插入pGEX-5T,重组蛋白、复性及纯化产物SDS聚丙烯酰胺凝胶电泳(SDS-PAGE)在84 000处有一条明显的蛋白表达条带,AMY2A检测具有酶活性,免疫印迹分析表明重组蛋白具有人胰腺淀粉酶抗原性。结论 作者已克隆并在大肠杆菌中初步表达并获得纯化的谷胱苷肽转移酶(GST)-AMY2A融合蛋白。     

Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage: an updated systemic review and meta-analysis

Introduction  

Previous meta-analyses of magnesium sulphate infusion in the treatment of aneurysmal subarachnoid hemorrhage (SAH) have become outdated due to recently published clinical trials. Our aim was thus to perform an up-to-date systemic review and meta-analysis of published data on the use of magnesium sulphate infusion in aneurysmal SAH patients.     

Prospective randomized study of mode switching in a clinical trial of pacemaker therapy for sinus node dysfunction

INTRODUCTION: Atrial fibrillation (AF) is common in pacemaker patients with sinus node dysfunction (SND) and may result in rapid ventricular pacing (RVP) in the DDDR mode. Mode switching (MS) reduces RVP, but its clinical benefit in patients with SND is unknown. METHODS AND RESULTS: Two hundred two patients in the Mode Selection Trial (MOST; 2,010-patient, 6-year trial of DDDR vs VVIR pacing in SND) randomized to DDDR pacemakers with atrial high-rate episode (AHRE) storage capabilities were subrandomized to MS ON (N = 96) or MS OFF (N = 106). Cardiovascular symptoms, quality of life (QOL), reprogramming due to RVP, death, stroke, and heart failure hospitalization (HFH) were compared between groups. The treatment groups were similar with regard to AF history (59% MS ON vs 57% MS OFF). AHREs occurred in 49% patients during median follow-up of 2.2 years. Median AHRE duration (in min; MS ON 116 vs MS OFF 58, P = 0.29), frequency AHREs/week (MS ON 3.5 vs MS OFF 6.4, P = 0.23), and time spent in AHRE (min/week) (MS ON 450, MS OFF 268) were similar. Reprogramming due to any RVP during AHREs occurred more in MS OFF vs MS ON (13.2% vs 3.1%, P = 0.011) and marginally more for symptomatic RVP (8.5% vs 2.1%, P = 0.062). Cardiovascular symptoms occurred in 93.6% MS ON vs 90.2% MS OFF (P = 0.38). Median number of symptoms reported per visit was similar (MS ON 1.3 vs MS OFF 1.5, P = 0.62). Median symptom frequency/severity, summed and averaged over visits, was similar (MS ON 4.3 vs MS OFF 4.5, P = 0.74). QOL was not different between groups. Death, stroke, and HFH were not different between groups. CONCLUSION: MS reduces pacemaker reprogramming due to RVP during AHREs in a small number of patients but does not improve QOL or cardiovascular symptoms overall among patients with SND.     

Self-assembly of soft-matter quasicrystals and their approximants

The surprising recent discoveries of quasicrystals and their approximants in soft-matter systems poses the intriguing possibility that these structures can be realized in a broad range of nanoscale and microscale assemblies. It has been theorized that soft-matter quasicrystals and approximants are largely entropically stabilized, but the thermodynamic mechanism underlying their formation remains elusive. Here, we use computer simulation and free-energy calculations to demonstrate a simple design heuristic for assembling quasicrystals and approximants in soft-matter systems. Our study builds on previous simulation studies of the self-assembly of dodecagonal quasicrystals and approximants in minimal systems of spherical particles with complex, highly specific interaction potentials. We demonstrate an alternative entropy-based approach for assembling dodecagonal quasicrystals and approximants based solely on particle functionalization and shape, thereby recasting the interaction-potential-based assembly strategy in terms of simpler-to-achieve bonded and excluded-volume interactions. Here, spherical building blocks are functionalized with mobile surface entities to encourage the formation of structures with low surface contact area, including non-close-packed and polytetrahedral structures. The building blocks also possess shape polydispersity, where a subset of the building blocks deviate from the ideal spherical shape, discouraging the formation of close-packed crystals. We show that three different model systems with both of these features-mobile surface entities and shape polydispersity-consistently assemble quasicrystals and/or approximants. We argue that this design strategy can be widely exploited to assemble quasicrystals and approximants on the nanoscale and microscale. In addition, our results further elucidate the formation of soft-matter quasicrystals in experiment.     

保存7天单采血小板的体外研究

本项研究的目的是确定单采血小板可允许保存的条件,包括容积、血小板成分的含量和特殊血小板成分保存袋内的血小板总量。材料和方法 本研究用单采机(COBE Spectra LRS Turbo,version 7,Gambro BCT,Denver,CO)从自愿献血者采集血小板成分,献血者符合 FDA和 AABB 献血标准,并在献血小板成分之前 7天内,没有服用改变血小板成分作用的药物和抗生素。控制每袋血小板成分的浓度和容积,以检测这些变量。悬浮在血浆中的血小板成分保存在特制的PVC合成的塑料袋中,枸椽酸钠抗凝,在22℃温控的恒温箱中震荡8天。     

17β-OESTRADIOL ENHANCES NITRIC OXIDE SYNTHASE ACTIVITY IN ENDOTHELIUM-DENUDED RAT AORTA

1. It has been suggested that oestrogen-produced vasodilatation is due to induction of endothelial nitric oxide synthase (NOS), but there are many reports of direct effects on vascular smooth muscle. In the present study, these processes were investigated in rat aorta isolated from ovariectomized rats. 2. Short-term treatment (10min) with 17β-oestradiol (10 μmol/L) produced a small attenuation of the phenylephrine (PE)-induced constriction, which was unaffected by the nitric oxide synthase inhibitor l-N 5(-1-iminoethyl)ornithine (NIO; 100μmol/L). Long-term treatment (6h) with 17β-oestradiol (10 μmol/L) did not affect acetylcholine-mediated vasorelaxation in endothelium-intact aortic rings, but did attenuate PE-induced constriction. This attenuation was also observed in endotheliumdenuded preparations after 17β-oestradiol (10 μmol/L for 6h) and was far greater than the acute effect of 17β-oestradiol (10 μmol/L). 3. The attenuation produced by 17β-oestradiol (10 μmol/L for 6 h) was significantly inhibited by concomitant treatment with cycloheximide (1 μmol/L), suggesting that protein synthesis was involved. NIO (100 μmol/L) also attenuated the effect, which suggests that the anti-constrictor effect of 17β-oestradiol occurs through the increased production of nitric oxide (NO). 17β-Oestradiol increased NO production, as assessed by the conversion of [³H]-arginine to [³H]-citrulline in rat aorta. These effects were prevented by cycloheximide and NIO. The anti-constrictor effect of oestrogen was blocked by the oestrogen receptor antagonist ICI 182780 (100nmol/L). 4. Western blotting using an antibody specific for inducible nitric oxide synthase (NOS) revealed that 17β-oestradiol (10 μmol/L for 24 h) treatment induced the formation of inducible NOS protein in the aorta, an effect blocked by cycloheximide. The results indicate that 17β-oestradiol can attenuate the vasoconstrictor effect of PE by a specific receptor-mediated process that involves induction of inducible NOS.