Sevoflurane protects cardiomyocytes against hypoxia/reperfusion injury via LINC01133/miR-30a-5p axis

Previous studies failed to elucidate the detailed mechanisms of anesthetic preconditioning as a protective approach against ischemic/reperfusion (I/R) injury in cells. The present study mainly centered on discovering the mechanisms of Sevoflurane (Sev) in preventing cardiomyocytes against I/R injury. Human cardiomyocyte AC16 cell line was used to simulate I/R injury based on a hypoxia/reperfusion (H/R) model. After Sev treatment, cell viability and apoptosis were detected by MTT assay and flow cytometry, respectively. Lactate dehydrogenase (LDH) content was measured using an LDH Detection Kit. Relative mRNA and protein expressions of LINC01133, miR-30a-5p and apoptosis-related proteins were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. Target gene of miR-30a-5p and their potential binding sites were predicted using Starbase and confirmed by dual-luciferase reporter assay. Cell behaviors were assessed again after miR-30a-5p and LINC01133 transfection. Sev could improve cell viability, reduce LDH leakage, and down-regulate the expressions of apoptosis-related proteins (Bax, cleaved caspase-3 and cleaved caspase-9) and LINC01133 as well as up-regulate miR-30a-5p and Bcl-2 expressions in H/R cells. MiR-30a-5p was the target of LINC01133, and up-regulating miR-30a-5p enhanced the effects of Sev in H/R cells, with a suppression on H/R-induced activation of the p53 signaling pathway. However, up-regulating LINC01133 reversed the enhancing effects of miR-30a-5p on Sev pretreatment in H/R cells. Sev could protect cardiomyocytes against H/R injury through the miR-30a-5p/LINC01133 axis, which may provide a possible therapeutic method for curing cardiovascular I/R injury.     

Optimal control strategies and cost-effectiveness analysis of a malaria model

The aim of this paper is to investigate the effectiveness and cost-effectiveness of three malaria preventive measures (use of treated bednets, spray of insecticides and a possible treatment of infective humans that blocks transmission to mosquitoes). For this, we consider a mathematical model for the transmission dynamics of the disease that includes these measures. We first consider the constant control parameters’ case, we calculate the basic reproduction number and investigate the existence and stability of equilibria; the model is found to exhibit backward bifurcation. We then assess the relative impact of each of the constant control parameters measures by calculating the sensitivity index of the basic reproductive number to the model's parameters. In the time-dependent constant control case, we use Pontryagin's Maximum Principle to derive necessary conditions for the optimal control of the disease. We also calculate the Infection Averted Ratio (IAR) and the Incremental Cost-Effectiveness Ratio (ICER) to investigate the cost-effectiveness of all possible combinations of the three control measures. One of our findings is that the most cost-effective strategy for malaria control, is the combination of the spray of insecticides and treatment of infective individuals. This strategy requires a 100% effort in both treatment (for 20 days) and spray of insecticides (for 57 days). In practice, this will be extremely difficult, if not impossible to achieve. The second most cost-effective strategy which consists of a 100% use of treated bednets and 87% treatment of infective individuals for 42 and 100 days, respectively, is sustainable and therefore preferable.     

Population statistics and biological traits of Hippodamia variegata (Goeze) (Coleoptera: Coccinellidae) affected by LC30 of thiamethoxam and pirimicarb

Although selective pesticides are recommended to use in integrated pest management (IPM) programmes, they could adversely affect biological agents. So, the aim of the current study was to investigate the LC₃₀ of pirimicarb and thiamethoxam on Hippodamia variegata. Two pesticides, pirimicarb and thiamethoxam, when applied at concentrations of 1522.8 and 251.3?mg (ai)/L, respectively, on the third instar larvae of the insect, produced 30% mortality. Also, results showed that neither pirimicarb nor thiamethoxam affect stage age distribution (c_x), fecundity (eggs/female) and adult development time. These two pesticides extended preadult duration significantly (p?<?0.0001, F?=?31.22, df?=?122). Also, survival rate (l_x) and age-specific reproductive value (v_x) decreased and some changes in age-specific life expectancy (e_x) happened. Generally, more adverse effects were found in the population treated by thiamethoxam. The results showed that pirimicarb and thiamethoxam have potential to harm the predatory ladybird in IPM programme, though in sublethal doses.     

Metal ion and inter-domain interactions as functional networks in E. coli topoisomerase I

Escherichia coli topoisomerase I (EcTopoI) is a type IA bacterial topoisomerase which is receiving large attention due to its potential application as novel target for antibacterial therapeutics. Nevertheless, a detailed knowledge of its mechanism of action at molecular level is to some extent lacking. This is partly due to the requirement of several factors (metal ions, nucleic acid) to the proper progress of the enzyme catalytic cycle. Additionally, each of them can differently affect the protein structure.     

丹参转录因子基因SmMYCamiRNA表达载体的构建及其对丹参的转化

丹参（Salvia miltiorrhiza Bunge）为我国传统中药,其活性成分的药理作用广泛,尤其在防治心血管病药物中具有重要作用。丹参水溶性酚酸类物质合成途径由苯丙烷代谢和酪氨酸代谢共同参与而成。转录因子对植物次生代谢起着十分重要的调节作用。我们前期测序结果显示,SmMyc是一个丹参bHLH类转录因子,可能参与丹参酚酸类化合物生物合成的调控。本研究利用拟南芥miRNA319前体为模板骨架,通过over-lappingPCR技术构建旨在能对SmMYC进行特异性沉默的at-tificalmiRNA（amiRNA）植物表达载体,命名为pCambial302-amiR-SmMYC,并通过农杆菌介导的遗传转化方法将其导入丹参。Real．timePCR结果显示,所得转化阳性株系SmMYC的mRNA水平均呈现不同程度的下降,同时酚酸类代谢途径中相关酶基因的表达也表现为相应程度的下调;福林酚法检测结果显示,转化株系中总酚酸含量均低于同期的野生型丹参。以上实验结果初步显示丹参SmMYC可能作为一个重要的转录因子参与酚酸类活性物质的代谢调控,同时为进一步研究SmMYC4丹参酚酸类化合物生物合成中的调控功能奠定了基础。     

30 nm染色质的体外组装和电镜分析

真核生物的基因组以染色质的形式存在,染色质在真核生物的基因表达调控及胚胎发育过程中起重要作用,为表观遗传提供一个重要的信息整合平台．染色质的高级结构,特别是 30 nm染色质的动态变化在基因转录沉默和激活过程中起着重要的调控功能．但是目前对30 nm 染色质纤维的组装及其精细结构的认识还十分有限．本文通过体外表达系统,表达未经修饰的组蛋白,并利用克隆构建的601DNA均一重复序列,通过逐步降低盐离子浓度并加入组蛋白H1或镁离子的方法,体外重组均一的30 nm染色质纤维．并利用镀金属、负染色制样和冷冻电镜制样等手段通过透射式电子显微镜(TEM)对30 nm纤维结构的形成原因、组蛋白H1的作用和核小体重复单位(nucleosome repeat lengths,NRLs)长度对30 nm染色质纤维的影响进行研究．研究结果显示在组蛋白H1或二价镁离子存在的情况下,均可形成30 nm染色质纤维．其形成的染色质拓扑结构有所不同．统计分析表明,不同长度核小体重复单位(NRLs)形成的染色质纤维直径有所不同(P < 0.05)．同时,我们得到了较为均一的冷冻电镜样品,为进一步研究30 nm染色质纤维的高级结构及理解体内染色质存在的形式及动态过程打下了较好的基础．