PMicroRNA-124a regulates LPS-induced septic cardiac dysfunction by targeting STX2

Objective

To examine the role of miR-124a in LPS-induced septic cardiac insufficiency where underlying mechanism is unclear.

Results

Expression of miR-124a was decreased in myocardium of LPS-induced septic cardiac dysfunction model. miR-124a antagomiR or agomiR were injected via tail vein to induce miR-124a-dysregulated model. miR-124a antagomiR aggravated LPS-induced cardiac dysfunction and apoptosis, while miR-124a agomiR had the opposite effect. Syntaxin-2 (STX2) was indicated as a candidate target gene by bioinformatic software. Further experiments confirmed that STX2 was downregulated in miR-124a agomiR-treated rats but upregulated in miR-124a antagomiR-treated rats, and STX2 inhibition could strongly block the miR-124a antagomiR-associated increase in cell apoptosis. Luciferase reporter activity assay indicated that STX2 was a direct target of miR-124a. Serological detection reveled that miR-124a was down-regulated in the plasma of septic cardiac dysfunction rats.

Conclusions

miR-124a aggravates LPS-induced cardiac dysfunction and the miR-124a/STX2 pathway might serve as the potential diagnostic and therapeutic targets for septic cardiac dysfunction.

     

Bioluminescent imaging of hepatocellular carcinoma in live mice

A non-invasive orthotopic hepatocellular carcinoma (HCC) model was created with human HCC cells (HepG-Luc) constitutively expressing luciferase (Luc) in nude mice. Development of tumor growth and response to anti-tumor therapy combined with 5-fluorouracil and cisplatin was monitored by whole-body bioluminescent imaging (BLI). Luciferase activity in the tumor, determined by BLI, correlated with the tumor volume and weight. The anti-tumor therapy proved effective by BLI monitoring. In conclusion, BLI by luciferase provides a non-invasive method of monitoring tumor activities that can prove useful for therapeutic intervention studies.     

植物乳杆菌天然质粒系统进化和起源

【目的】为了探索植物乳杆菌天然质粒系统进化关系和起源。【方法】本文利用复制起始蛋白(replication initiation protein,Rep)系统进化树、基因组共线性、基因组GC含量和宿主范围分析方法,对植物乳杆菌75个天然质粒的系统进化关系和起源进行了详细和多角度的分析。【结果】首先,Rep系统进化树和基因组共线性分析结果均表明,植物乳杆菌所有天然质粒可以划分为6个进化关系亲密的家族、2个进化形态特殊的杂合质粒和1个独立进化质粒pLP2140。杂合质粒pMRI5.2、pLP12-1分别由家族1-2和5-6质粒融合形成,因此植物乳杆菌质粒可能起源于7个祖先。其次,基因组共线性分析可以将6个家族质粒进一步划分为17个进化关系更近的亚家族类群,并清晰、有效地揭示类群内质粒之间的系统进化关系。最后,基因组GC含量和宿主范围分析为植物乳杆菌质粒的系统进化关系和起源提供了进一步的证据。【结论】因此上述研究可以准确、有效地揭示植物乳杆菌天然质粒的系统进化关系和起源,这对植物乳杆菌天然质粒系统进化和起源的了解和研究具有重要的参考价值。通过Rep系统进化树和基因组共线性两种分析方法优缺点的比较和组合,我们提出了一种更加有效的研究思路和分析方法,同时这种方法很可能适用于所有细菌天然质粒,因此对于天然质粒进化和起源研究具有普遍的方法学意义。     

Viral tegument proteins restrict cGAS-DNA phase separation to mediate immune evasion

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Stable Li Metal Anode Enabled by Space Confinement and Uniform Curvature through Lithiophilic Nanotube Arrays

The application of lithium (Li) metal anodes in rechargeable batteries is primarily restricted by Li dendrite growth on the metal's surface, which leads to shortened cycle life and safety concerns. Herein, well‐spaced nanotubes with ultrauniform surface curvature are introduced as a Li metal anode structure. The ultrauniform nanotubular surface generates uniform local electric fields that evenly attract Li‐ions to the surface, thereby inducing even current density distribution. Moreover, the well‐defined nanotube spacing offers Li diffusion pathways to the electroactive areas as well as the confined spaces to host deposited Li. These structural attributes create a unique electrodeposition manner; i.e., Li metal homogenously deposits on the nanotubular wall, causing each Li nanotube to grow in circumference without obvious sign of dendritic formation. Thus, the full‐cell battery with the spaced Li nanotubes exhibits a high specific capacity of 132 mA h g^?1 at 1 C and an excellent coulombic efficiency of ≈99.85% over 400 cycles.     

Impact of nonrandom selection mechanisms on the causal effect estimation for two-sample Mendelian randomization methods

Nonrandom selection in one-sample Mendelian Randomization (MR) results in biased estimates and inflated type I error rates only when the selection effects are sufficiently large. In two-sample MR, the different selection mechanisms in two samples may more seriously affect the causal effect estimation. Firstly, we propose sufficient conditions for causal effect invariance under different selection mechanisms using two-sample MR methods. In the simulation study, we consider 49 possible selection mechanisms in two-sample MR, which depend on genetic variants (G), exposures (X), outcomes (Y) and their combination. We further compare eight pleiotropy-robust methods under different selection mechanisms. Results of simulation reveal that nonrandom selection in sample II has a larger influence on biases and type I error rates than those in sample I. Furthermore, selections depending on X+Y, G+Y, or G+X+Y in sample II lead to larger biases than other selection mechanisms. Notably, when selection depends on Y, bias of causal estimation for non-zero causal effect is larger than that for null causal effect. Especially, the mode based estimate has the largest standard errors among the eight methods. In the absence of pleiotropy, selections depending on Y or G in sample II show nearly unbiased causal effect estimations when the casual effect is null. In the scenarios of balanced pleiotropy, all eight MR methods, especially MR-Egger, demonstrate large biases because the nonrandom selections result in the violation of the Instrument Strength Independent of Direct Effect (InSIDE) assumption. When directional pleiotropy exists, nonrandom selections have a severe impact on the eight MR methods. Application demonstrates that the nonrandom selection in sample II (coronary heart disease patients) can magnify the causal effect estimation of obesity on HbA1c levels. In conclusion, nonrandom selection in two-sample MR exacerbates the bias of causal effect estimation for pleiotropy-robust MR methods.