A Human Active Lower Limb Model for Chinese Pedestrian Safety Evaluation

A subsystem impactor test for pedestrian lower limb injury evaluation has been brought in China New Car Assessment Protocol(CNCAP).Concerning large anthropometr...     

3,3′,4,5′-Tetramethoxy-trans-stilbene Improves Insulin Resistance by Activating the IRS/PI3K/Akt Pathway and Inhibiting Oxidative Stress

The potential anti-diabetic effect of resveratrol derivative, 3,3′,4,5′-tetramethoxy-trans-stilbene (3,3′,4,5′-TMS) and its underlying mechanism in high glucose (HG) and dexamethasone (DXMS)-stimulated insulin-resistant HepG2 cells (IR-HepG2) were investigated. 3,3′,4,5′-TMS did not reduce the cell viability of IR-HepG2 cells at the concentrations of 0.5–10 µM. 3,3′,4,5′-TMS increased the potential of glucose consumption and glycogen synthesis in a concentration-dependent manner in IR-HepG2 cells. 3,3′,4,5′-TMS ameliorated insulin resistance by enhancing the phosphorylation of glycogen synthase kinase 3 beta (GSK3β), inhibiting phosphorylation of insulin receptor substrate-1 (IRS-1), and activating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in IR-HepG2 cells. Furthermore, 3,3′,4,5′-TMS significantly suppressed levels of reactive oxygen species (ROS) with up-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) expression. To conclude, the beneficial effect of 3,3′,4,5′-TMS against insulin resistance to increase glucose consumption and glycogen synthesis was mediated through activation of IRS/PI3K/Akt signaling pathways in the IR-HepG2 cells, accomplished with anti-oxidative activity through up-regulation of Nrf2.     

Using genetic variation to disentangle the complex relationship between food intake and health outcomes

Diet is considered as one of the most important modifiable factors influencing human health, but efforts to identify foods or dietary patterns associated with health outcomes often suffer from biases, confounding, and reverse causation. Applying Mendelian randomization in this context may provide evidence to strengthen causality in nutrition research. To this end, we first identified 283 genetic markers associated with dietary intake in 445,779 UK Biobank participants. We then converted these associations into direct genetic effects on food exposures by adjusting them for effects mediated via other traits. The SNPs which did not show evidence of mediation were then used for MR, assessing the association between genetically predicted food choices and other risk factors, health outcomes. We show that using all associated SNPs without omitting those which show evidence of mediation, leads to biases in downstream analyses (genetic correlations, causal inference), similar to those present in observational studies. However, MR analyses using SNPs which have only a direct effect on the exposure on food exposures provided unequivocal evidence of causal associations between specific eating patterns and obesity, blood lipid status, and several other risk factors and health outcomes.     

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.Subject terms: Cell death, Molecular biology     

TEB/POLQ plays dual roles in protecting Arabidopsis from NO-induced DNA damage

Nitric oxide (NO) is a key player in numerous physiological processes. Excessive NO induces DNA damage, but how plants respond to this damage remains unclear. We screened and identified an Arabidopsis NO hypersensitive mutant and found it to be allelic to TEBICHI/POLQ, encoding DNA polymerase θ. The teb mutant plants were preferentially sensitive to NO- and its derivative peroxynitrite-induced DNA damage and subsequent double-strand breaks (DSBs). Inactivation of TEB caused the accumulation of spontaneous DSBs largely attributed to endogenous NO and was synergistic to DSB repair pathway mutations with respect to growth. These effects were manifested in the presence of NO-inducing agents and relieved by NO scavengers. NO induced G2/M cell cycle arrest in the teb mutant, indicative of stalled replication forks. Genetic analyses indicate that Polθ is required for translesion DNA synthesis across NO-induced lesions, but not oxidation-induced lesions. Whole-genome sequencing revealed that Polθ bypasses NO-induced base adducts in an error-free manner and generates mutations characteristic of Polθ-mediated end joining. Our experimental data collectively suggests that Polθ plays dual roles in protecting plants from NO-induced DNA damage. Since Polθ is conserved in higher eukaryotes, mammalian Polθ may also be required for balancing NO physiological signaling and genotoxicity.     

两种麻疯树苗对盐胁迫的生理生态响应

研究两种不同基因型麻疯树苗(南油2、3号)在不同NaCl浓度下生理生态响应特征,并比较不同基因型麻疯树苗的耐盐差异性。结果表明:①用25、50 mmo.lL-1NaCl处理,南油2号全株干重与对照无显著差异,而南油3号全株干重比对照显著降低。用100 mmol.L-1l或以上浓度的NaCl处理,随着盐度增加,两种树苗全株干重皆比对照显著降低,且3号苗降低的幅度大于2号苗。②在用200 mmol.L-1或以下浓度的NaCl处理,南油2、3号叶片相对含水量(RWC)皆与对照无显著差异,而在用300 mmol.L-1NaCl处理,则分别比对照显著降低5%和8%。③用25、50 mmol.L-1NaCl处理,南油2号可溶性糖(SS)含量比对照显著降低,3号与对照无显著差异;用200、300 mmo.lL-1NaCl处理后,两者SS含量均比对照显著降低。同时,2号苗可溶性蛋白(SP)含量比对照显著增加,3号苗SP含量与对照无显著差异。④随着盐度增加,南油2号苗超氧化物歧化酶(SOD)活性先增加后降低。用300 mmol.L-1NaCl处理,比对照显著降低。随着盐度增加,3号苗的SOD活性递减,皆显著低于对照。用25、50 mmo.lL-1NaCl处理,两种树苗的过氧化物酶(POD)活性与对照无显著差异。随着盐度增加,2号苗的POD活性比对照显著增加,而3号苗比对照显著降低。用25、50 mmo.lL-1NaCl处理,两种树苗的过氧化氢酶(CAT)活性皆比对照显著增加,且随着盐度增加,其变化趋势如SOD活性。结果表明,麻疯树幼苗具有较好的耐盐性,且南油2号比南油3号具有更高的耐盐性,因为前者具有更高的保护酶活性、叶片保水能力和叶片SP含量。     

黄土高原沟壑区王东沟小流域土壤有机碳空间分布

地貌和土地利用是影响土壤有机碳(Soil organic carbon,SOC)空间变异的重要因素。以黄土高原沟壑区王东沟小流域(8.3 km2)为对象,在考虑地貌单元和土地利用影响的基础上,采集0—20cm样品448个,0—200cm样品33个。研究了地貌单元(塬面、塬坡和沟道)和土地利用方式对SOC含量的影响。结果表明,地貌单元和土地利用对小流域表层和深层SOC的含量分布影响都有显著差异。0—20cm土层的SOC含量,沟道塬面塬坡;塬面表层SOC含量的变化平缓;塬坡和沟道SOC变异大于塬面。0—200cm土层SOC三地貌单元差异达极显著水平(P99.9%),塬面SOC含量最高(5.37g kg-1),塬坡(3.06 gkg-1)最低。不同地貌单元条件下土地利用方式对表层和剖面SOC含量分布的影响也存在明显差异。塬面区,人工草地SOC含量亦明显高于农田和果园,但仅40cm以上土层SOC达到显著差异。在塬坡上,不同土地利用类型间,发生显著差异深度达到140cm。沟道内,林草两种土地利用类型间的SOC含量无显著差异。在估算该地区SOC密度和储量时,需要充分考虑地貌单元和土地利用方式的影响。