Long non-coding RNA DANCR modulates osteogenic differentiation by regulating the miR-1301-3p/PROX1 axis

The balance of osteoblasts and marrow adipocytes from bone marrow mesenchymal stem cells (BM-MSCs) maintains bone health. Under aging or other pathological stimuli, BM-MSCs will preferentially differentiate into marrow adipocytes and reduce osteoblasts, leading to osteoporosis. Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) participates in the osteogenic differentiation of human BM-MSCs, but the mechanism by which DANCR regulates the osteogenic differentiation of human BM-MSCs has not been fully explained. We observed that DANCR and prospero homeobox 1 (PROX1) were downregulated during osteogenic differentiation of human BM-MSCs, while miR-1301-3p had an opposite trend. DANCR overexpression decreased the levels of alkaline phosphatase, RUNX2, osteocalcin, Osterix in BM-MSCs after osteogenic induction, but DANCR silencing had the opposite result. Moreover, DANCR sponged miR-1301-3p to regulate PROX1 expression. miR-1301-3p overexpression reversed the suppressive role of DANCR elevation on the osteogenic differentiation of human BM-MSCs. Also, PROX1 elevation abolished the promoting role of miR-1301-3p overexpression on the osteogenic differentiation of human BM-MSCs. In conclusion, DANCR suppressed the osteogenic differentiation of human BM-MSCs through the miR-1301-3p/PROX1 axis, offering a novel mechanism by which DANCR is responsible for the osteogenic differentiation of human BM-MSCs.

     

Preventing an Antigenically Disruptive Mutation in Egg-Based H3N2 Seasonal Influenza Vaccines by Mutational Incompatibility

1. Download : Download high-res image (235KB)
2. Download : Download full-size image

     

The JAK–STAT Pathway Is Critical in Ventilator-Induced Diaphragm Dysfunction

Mechanical ventilation (MV) is one of the lynchpins of modern intensive-care medicine and is life saving in many critically ill patients. Continuous ventilator support, however, results in ventilation-induced diaphragm dysfunction (VIDD) that likely prolongs patients’ need for MV and thereby leads to major associated complications and avoidable intensive care unit (ICU) deaths. Oxidative stress is a key pathogenic event in the development of VIDD, but its regulation remains largely undefined. We report here that the JAK–STAT pathway is activated in MV in the human diaphragm, as evidenced by significantly increased phosphorylation of JAK and STAT. Blockage of the JAK–STAT pathway by a JAK inhibitor in a rat MV model prevents diaphragm muscle contractile dysfunction (by ~85%, p < 0.01). We further demonstrate that activated STAT3 compromises mitochondrial function and induces oxidative stress in vivo, and, interestingly, that oxidative stress also activates JAK–STAT. Inhibition of JAK–STAT prevents oxidative stress-induced protein oxidation and polyubiquitination and recovers mitochondrial function in cultured muscle cells. Therefore, in ventilated diaphragm muscle, activation of JAK–STAT is critical in regulating oxidative stress and is thereby central to the downstream pathogenesis of clinical VIDD. These findings establish the molecular basis for the therapeutic promise of JAK–STAT inhibitors in ventilated ICU patients.     

In vitro assembly of multiple DNA fragments using successive hybridization

Construction of recombinant DNA from multiple fragments is widely required in molecular biology, especially for synthetic biology purposes. Here we describe a new method, successive hybridization assembling (SHA) which can rapidly do this in a single reaction in vitro. In SHA, DNA fragments are prepared to overlap one after another, so after simple denaturation-renaturation treatment they hybridize in a successive manner and thereby assemble into a recombinant molecule. In contrast to traditional methods, SHA eliminates the need for restriction enzymes, DNA ligases and recombinases, and is sequence-independent. We first demonstrated its feasibility by constructing plasmids from 4, 6 and 8 fragments with high efficiencies, and then applied it to constructing a customized vector and two artificial pathways. As SHA is robust, easy to use and can tolerate repeat sequences, we expect it to be a powerful tool in synthetic biology.     

Chloride Co-transporter NKCC1 Inhibitor Bumetanide Enhances Neurogenesis and Behavioral Recovery in Rats After Experimental Stroke

Bumetanide, a selective Na⁺-K⁺-Cl^?-co-transporter inhibitor, is widely used in clinical practice as a loop diuretic. In addition, bumetanide has been reported to attenuate ischemia-induced cerebral edema and reduce neuronal injury. This study examined whether bumetanide could influence neurogenesis and behavioral recovery in rats after experimentally induced stroke. Adult male Wistar rats were randomly assigned to four groups: sham, sham treated with bumetanide, ischemia, and ischemia treated with bumetanide. Focal cerebral ischemia was induced by injection of endothelin-1. Bumetanide (0.2 mg/kg/day) was infused into the lateral ventricle with drug administration being initiated 1 week after ischemia and continued for 3 weeks. Behavioral impairment and recovery were evaluated by tapered/ledged beam-walking test on post-stroke days 28. Then, the rats were perfused for BrdU/DCX (neuroblast marker), BrdU/NeuN (neuronal marker), BrdU/GFAP (astrocyte marker), and BrdU/Iba-1 (microglia marker) immunohistochemistry. The numbers of neuroblasts in the subventricular zone (SVZ) were significantly increased after the experimentally induced stroke. Bumetanide treatment increased migration of neuroblasts in the SVZ towards the infarct area, enhanced long-term survival of newborn neurons, and improved sensorimotor recovery, but it did not exert any effects on inflammation. In conclusion, our results demonstrated that chronic bumetanide treatment enhances neurogenesis and behavioral recovery after experimentally induced stroke in rats.     

星云湖硅藻群落响应近现代人类活动与气候变化的过程

随着人类活动的增强与全球气候变暖的持续,近年来云南湖泊的生态系统功能持续退化,而目前对云南湖泊生态系统的研究还主要集中于单一环境压力的生态效应。以星云湖为研究对象,通过沉积物记录与现代监测资料,识别在湖泊富营养化、气候变化以及人类强烈干扰下硅藻群落结构响应的过程,并甄别驱动群落变化的主要环境压力及其强度。结果显示随着湖泊生产力水平(如沉积物叶绿素a浓度)的增加,硅藻物种组成发生了明显的变化,主成分分析表明了水体富营养化是驱动群落变化的主要环境因子(r=-0.63,P0.001)。简约模型与方差分解的结果表明近200年来(钻孔长度38cm),湖泊营养水平和水动力是驱动星云湖硅藻群落变化的主要环境因子,分别解释了群落变化的18.8%和2.9%;而1951年以后,湖泊营养水平和温度分别解释了硅藻群落结构变化的31.4%和26.8%。研究结果表明了硅藻群落长期变化的主控因子是湖泊营养水平,而人类活动及气候变化等可以通过改变湖泊水动力及湖水温度来驱动硅藻群落的演替,同时抚仙湖-星云湖的连通性也对硅藻群落的演替产生了一定影响。     

Aneurysm Characteristics Associated with the Rupture Risk of Intracranial Aneurysms: A Self-Controlled Study

This study analyzed the rupture risk of intracranial aneurysms (IAs) according to aneurysm characteristics by comparing the differences between two aneurysms in different locations within the same patient. We utilized this self-controlled model to exclude potential interference from all demographic factors to study the risk factors related to IA rupture. A total of 103 patients were diagnosed with IAs between January 2011 and April 2015 and were enrolled in this study. All enrolled patients had two IAs. One IA (the case) was ruptured, and the other (the control) was unruptured. Aneurysm characteristics, including the presence of a daughter sac, the aneurysm neck, the parent artery diameter, the maximum aneurysm height, the maximum aneurysm width, the location, the aspect ratio (AR, maximum perpendicular height/average neck diameter), the size ratio (SR, maximum aneurysm height/average parent diameter) and the width/height ratio (WH ratio, maximum aneurysm width/maximum aneurysm height), were collected and analyzed to evaluate the rupture risks of the two IAs within each patient and to identify the independent risk factors associated with IA rupture. Multivariate, conditional, backward, stepwise logistic regression analysis was performed to identify the independent risk factors associated with IA rupture. The multivariate analysis identified the presence of a daughter sac (odds ratio [OR], 13.80; 95% confidence interval [CI], 1.65–115.87), a maximum aneurysm height ≥7 mm (OR, 4.80; 95% CI, 1.21–18.98), location on the posterior communicating artery (PCOM) or anterior communicating artery (ACOM; OR, 3.09; 95% CI, 1.34–7.11) and SR (OR, 2.13; 95% CI, 1.16–3.91) as factors that were significantly associated with IA rupture. The presence of a daughter sac, the maximum aneurysm height, PCOM or ACOM locations and SR (>1.5±0.7) of unruptured IAs were significantly associated with IA rupture.     

铜镉污染土壤上CO2浓度升高对籼稻稻米品质的影响

采用盆栽试验,利用开顶式气室(Open Top Chamber,OTC)研究了5个籼稻品种在高、低铜镉复合污染土壤上,CO2浓度升高对水稻生长及吸收Cu、Cd和矿质元素Fe、Zn、Ca、Mn的影响,并对稻米中Cd的安全性进行了评价,了解Cd污染对人类健康的潜在风险。结果表明:CO2浓度升高,显著降低了低复合污染土壤上稻米的生物量,而显著增加了高复合污染土壤上的稻米生物量。CO2浓度升高降低了低污染土壤上稻米Cu含量,降低幅度为4.75%—24.49%,增加了高污染土壤上稻米Cu含量,增加幅度为6.60%—40.37%;而稻米Cu的总吸收量在低、高复合污染土壤上均是降低的。低、高复合污染土壤上,CO2浓度升高显著降低了三香优974稻米的Cd含量和吸收量;增加了其他4个品种稻米Cd含量和吸收量。CO2浓度升高对不同品种稻米中Fe、Zn、Ca、Mn含量影响存在显著差异。CO2浓度正常、升高条件下,两种污染土壤上金优463稻米中Cd含量超过食品卫生标准(Cd≤0.2mg/kg),三香优974在正常CO2浓度条件下其稻米Cd含量超过食品卫生标准。在低、高复合污染土壤上,金优463和三香优974稻米中Cd的THQ值均大于1,说明对人体暴露接触的潜在风险比较严重。CO2浓度升高显著降低了三香优974稻米中Cd对人体暴露接触的潜在风险,而对其他4个水稻品种稻米Cd的THQ值影响不明显。     

2,4‐D‐induced parthenocarpy in pear is mediated by enhancement of GA4 biosynthesis

Parthenocarpy, the productions of seedless fruit without pollination or fertilization, is a potentially desirable trait in many commercially grown fruits, especially in pear, which is self‐incompatible. Phytohormones play important roles in fruit set, a process crucial for parthenocarpy. In this study, 2,4‐dichlorophenoxyacetic acid (2,4‐D), an artificially synthesized plant growth regulator with functions similar to auxin, was found to induce parthenocarpy in pear. Histological observations revealed that 2,4‐D promoted cell division and expansion, which increased cortex thickness, but the effect was weakened by paclobutrazol (PAC), a gibberellin (GA) biosynthesis inhibitor. Phenotypic differences in pear may therefore be due to different GA contents. Hormone testing indicated that 2,4‐D mainly induced the production of bioactive GA₄, rather than GA_3. Three key oxidase genes function in the GA biosynthetic pathway: GA20ox, GA3ox and GA2ox. In a pear group treated with only 2,4‐D, PbGA20ox2‐like and PbGA3ox‐1 were significantly upregulated. When treated with 2,4‐D supplemented with PAC, however, expression levels of these genes were significantly downregulated. Additionally, PbGA2ox1‐like and PbGA2ox2‐like expression levels were significantly downregulated in pear treated with either 2,4‐D only or 2,4‐D supplemented with PAC. We thus hypothesize that 2,4‐D can induce parthenocarpy by enhancing GA₄ biosynthesis.