Kernel energy method: application to insulin

In two recent articles a method has been described for calculating the total energy of large molecules. The method is called the kernel energy method (KEM) and requires knowledge of the crystal structure of interest. Calculations are simplified by adopting the approximation that a full molecule could be represented by smaller kernels of atoms. The KEM was illustrated with peptides ranging in size from 4 to 19 amino acid residues, and was found to deliver accurate results. The use of the KEM does not depend upon a particular choice of basis functions and is applicable across quantum computational methods of differing levels of accuracy. These earlier investigations suggested that the KEM could be used to calculate the ab initio quantum mechanical energy of proteins. An application has been made with the protein insulin, composed of 51 aa. Accurate KEM Hartree-Fock energies are obtained for the separate A and B chains of insulin and for their composite structure in the full insulin molecule. A limited basis is used to make possible calculation of the full insulin molecule, which can be used as a standard of accuracy for the KEM calculation. The KEM result obtained is E(KEM) = -21104.7656 a.u. It differs from a full molecule Hartree-Fock result by only 0.000002%. The solvent molecules can be treated effectively as a separate kernel. The KEM result for the fully solvated insulin molecule is E(KEM) = -26275.4127 a.u., differing from the full molecule Hartree-Fock result by as little as 0.000023%.     

The rejection of science frames in the news coverage of the golden rice experiment in Hunan,China

In this article, we examine the ways in which media frames and rhetorical devices in the Chinese media shaped the representation of the genetically modified (GM) golden rice. We draw on a study of Chinese media representations of an experiment designed to test the efficacy of golden rice as a source of Vitamin A using school children in China’s Hunan province as subjects. The study analysed Chinese web news stories about the Hunan experiment posted between 30 August 2012 (when Greenpeace first reported on the issue) and 30 October 2012. This experiment resulted in allegations of breaches in scientific protocols and created a hostile public reaction. The incident fuelled the long-standing debate about the risks and benefits of GM crops in China. In this article, we analyse 25 online news reports, examining the attitudinal orientation of the articles, the readers’ comments on the articles and GM crops, the writing style and rhetorical devices employed, the emotions provoked and the frames manifest and embedded in these articles and comments. We found that although only one-third of the articles manifested an obviously negative attitude towards golden rice and GM foods, their use of strident metaphors and analogies were designed to arouse readers’ fear and concerns about GM crops. In the anti-golden rice articles, we identified conspiracy frames, including the view that the West was using genetic engineering to establish global control over agriculture and that GM products were instruments for genocide. The pro-golden rice articles emphasised the scientific humanitarian progress, but it appears to be less attractive to the readers.     

LncRNA NEXN-AS1 attenuates proliferation and migration of vascular smooth muscle cells through sponging miR-33a/b

Non-protein-coding RNAs (lncRNAs) are emerging as important regulators in disease pathogenesis, including atherosclerosis (AS). Here, we investigated the role and underlying mechanisms of nexilin F-actin binding protein antisense RNA 1 (NEXN-AS1) on the proliferation and migration of vascular smooth muscle cells (VSMCs). Our data revealed that ox-LDL treatment resulted in decreased NEXN-AS1 expression and increased miR-33a/b levels in human aorta VSMCs (HA-VSMCs) in dose- and time-dependent manners. Overexpression of NEXN-AS1 mitigated the proliferation and migration of HA-VSMCs under ox-LDL stimulation using CCK-8 and wound-healing assays. Moreover, dual-luciferase reporter and RNA immunoprecipitation assays verified that NEXN-AS1 acted as molecular sponges of miR-33a and miR-33b in HA-VSMCs. MiR-33a or miR-33b silencing attenuated the proliferation and migration of ox-LDL-treated HA-VSMCs. Furthermore, miR-33a or miR-33b mediated the inhibitory effects of NEXN-AS1 overexpression on the proliferation and migration of ox-LDL-treated HA-VSMCs. Our study suggested that high level of NEXN-AS1 mitigated VSMC proliferation and migration under ox-LDL stimulation at least partly through sponging miR-33a and miR-33b, illuminating NEXN-AS1 as a novel therapeutic approach for AS treatment.

Non-protein-coding RNAs (lncRNAs) are emerging as important regulators in disease pathogenesis, including atherosclerosis (AS).     

Implementation and impact of a multidisciplinary coagulation factor stewardship program at an academic medical center

Journal of Thrombosis and Thrombolysis -     

Subpicomolar diphenyleneiodonium inhibits microglial NADPH oxidase with high specificity and shows great potential as a therapeutic agent for neurodegenerative diseases

Activation of microglial NADPH oxidase (NOX2) plays a critical role in mediating neuroinflammation, which is closely linked with the pathogenesis of a variety of neurodegenerative diseases, including Parkinson's disease (PD). The inhibition of NOX2‐generated superoxide has become an effective strategy for developing disease‐modifying therapies for PD. However, the lack of specific and potent NOX2 inhibitors has hampered the progress of this approach. Diphenyleneiodonium (DPI) is a widely used, long‐acting NOX2 inhibitor. However, due to its non‐specificity for NOX2 and high cytotoxicity at standard doses (µM), DPI has been precluded from human studies. In this study, using ultra‐low doses of DPI, we aimed to: (1) investigate whether these problems could be circumvented and (2) determine whether ultra‐low doses of DPI were able to preserve its utility as a potent NOX2 inhibitor. We found that DPI at subpicomolar concentrations (10^?14 and 10^?13 M) displays no toxicity in primary midbrain neuron‐glia cultures. More importantly, we observed that subpicomolar DPI inhibited phorbol myristate acetate (PMA)‐induced activation of NOX2. The same concentrations of DPI did not inhibit the activities of a series of flavoprotein‐containing enzymes. Furthermore, potent neuroprotective efficacy was demonstrated in a post‐treatment study. When subpicomolar DPI was added to neuron‐glia cultures pretreated with lipopolysaccharide, 1‐methyl‐4‐phenylpyridinium or rotenone, it potently protected the dopaminergic neurons. In summary, DPI's unique combination of high specificity toward NOX2, low cytotoxicity and potent neuroprotective efficacy in post‐treatment regimens suggests that subpicomolar DPI may be an ideal candidate for further animal studies and potential clinical trials. GLIA 2014;62:2034–2043     

高校职工糖尿病前期干预研究

目的探讨生活干预联合药物控制延缓糖尿病前期发展为糖尿病的程度。方法对2011年6月某高校体检确诊为糖尿病前期200例职工进行观察,随机分为干预组(生活干预+药物控制)与对照组,观察期限为2年,比较两组患者1年后、2年后基础信息和糖尿病患病率。结果两组糖尿病前期职工干预前基础信息比较差异无统计学意义;观察组1年后糖尿病患病率为1%,对照组为13%,差异有统计学意义(x2=11.06,P0.01);观察组2年后糖尿病患病率为2%,对照组为20%,差异有统计学意义(x2=11.06,P0.01)。结论生活干预联合药物控制可能延缓糖尿病前期发展为糖尿病。     

珊瑚骨粉复合组织补片进行拔牙位点保存的临床研究

目的探讨使用珊瑚骨粉复合组织补片进行拔牙位点保存的临床效果。方法选取自2012年12月至2014年2月期间在武警总医院口腔种植科门诊采用微创技术拔除磨牙的患者45例,试验组20例,拔牙窝内植入珊瑚骨粉,组织补片覆盖表面关闭拔牙窝;对照组25例,拔牙后常规处理。1、3、6个月复诊,观察拔牙窝愈合情况。拔牙前及拔牙6个月后进行口内取模灌注石膏模型并拍摄X线牙片,分别测量牙槽嵴的高度和宽度,使用配对t检验分别对两组拔牙前至6个月期间牙槽嵴高度、宽度的变化进行统计学分析,使用两独立样本的t检验进行两组间牙槽嵴高度、宽度变化的比较,P〈0.05为差异具有统计学意义。结果临床观察除有一例组织补片脱落外,试验组其他拔牙窝均愈合良好,牙槽骨丰满,牙龈色、形、质与邻牙协调;而对照组牙槽嵴吸收、萎缩,高度降低、宽度显著缩小。统计学分析试验组牙槽嵴高度和宽度的改变无显著的统计学差异（P〉0.05）;对照组的上述改变具有统计学差异（P〈0.05）。两组间牙槽嵴高度、宽度的变化相比,二者间的差异均具有统计学意义（P〈0.05）。结论珊瑚骨粉复合组织补片有效保存了进行种植牙修复所必需的骨量,是进行拔牙后位点保存术的合适材料。     

非药物干预比较改善ICU患者睡眠质量效果的网状Meta分析

目的采用网状Meta分析方法评价非药物干预改善ICU患者睡眠质量的效果。方法计算机检索The Cochrane Library、PubMed、EMbase、Web of Science、CNKI、WanFang Data、VIP和CBM数据库,搜集非药物干预改善ICU患者睡眠质量效果的随机对照试验(RCT),检索时限均为建库至2018年12月。由2名研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用Stata 13.0软件进行网状Meta分析。结果共纳入12个RCT,包括1223例患者,涉及9种非药物干预方法(音乐疗法、综合护理干预、中医情志、音乐疗法+中医情志、中药枕疗法、耳穴压豆、眼罩+耳塞+音乐、眼罩+耳塞、常规护理)。针对匹兹堡睡眠质量指数(PSQI)的网状Meta分析结果显示:在改善ICU患者睡眠质量方面,眼罩+耳塞、眼罩、综合护理干预优于常规护理,其差异有统计学意义。结果排序图显示:眼罩+耳塞>眼罩>综合护理干预、音乐疗法+中医情志>中医情志>音乐疗法>常规护理。针对Richards-Campbell睡眠量表(RCSQ)的网状Meta分析结果显示:眼罩+耳塞+音乐、中药枕疗法、耳穴压豆优于常规护理,其差异有统计学意义。结果排序图显示:眼罩+耳塞+音乐>中药枕疗法>音乐疗法>耳穴压豆>常规护理。结论当前证据显示,在改善ICU患者睡眠质量方面,眼罩+耳塞、眼罩、综合护理干预、音乐疗法+中医情志都可能是有效的干预方式,建议未来开展更多非药物干预改善ICU患者睡眠质量效果的RCT。