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...     

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.     

Caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research

Acute lung injury (ALI) is a potentially life-threatening, devastating disease with an extremely high rate of mortality. The underlying mechanism of ALI is currently unclear. In this study, we aimed to confirm the hub genes associated with ALI and explore their functions and molecular mechanisms using bioinformatics methods. Five microarray datasets available in GEO were used to perform Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs) and the key genes were identified via the protein-protein interaction (PPI) network. Lipopolysaccharide intraperitoneal injection was administered to establish an ALI model. Overall, 40 robust DEGs, which are mainly involved in the inflammatory response, protein catabolic process, and NF-κB signaling pathway were identified. Among these DEGs, we identified two genes associated with ALI, of which the CAV-1/NF-κB axis was significantly upregulated in ALI, and was identified as one of the most effective targets for ALI prevention. Subsequently, the expression of CAV-1 was knocked down using AAV-shCAV-1 or CAV-1-siRNA to study its effect on the pathogenesis of ALI in vivo and in vitro. The results of this study indicated that CAV-1/NF-κB axis levels were elevated in vivo and in vitro, accompanied by an increase in lung inflammation and autophagy. The knockdown of CAV-1 may improve ALI. Mechanistically, inflammation was reduced mainly by decreasing the expression levels of CD3 and F4/80, and activating autophagy by inhibiting AKT/mTOR and promoting the AMPK signaling pathway. Taken together, this study provides crucial evidence that CAV-1 knockdown inhibits the occurrence of ALI, suggesting that the CAV-1/NF-κB axis may be a promising therapeutic target for ALI treatment.Subject terms: Cell signalling, Respiratory tract diseases     

短期增温对中亚热带杉木人工幼林土壤氮磷耦合作用的影响

全球变暖引起陆地生态系统和整个生物圈一系列生态问题,未来全球平均气温的持续增加将使这些问题进一步加剧。目前增温、氮沉降和森林更新方式对中亚热带土壤氮磷等养分的影响已有部分研究,但增温对亚热带森林的氮磷耦合作用的影响仍然未知。以中亚热带杉木(Cunninghamia lanceolate)幼苗为研究对象,设置埋设电缆以加热土壤增温实验(增温幅度(5±0.5)℃),研究短期增温对土壤含水量、微生物生物量氮(MBN)、微生物生物量磷(MBP)、土壤氮磷养分,以及氮(N)、磷(P)耦合作用的影响。结果表明:短期增温对全氮、全磷无显著影响;增温第1年显著提高了有效氮、铵态氮(NH_4~+)和有效磷的含量,显著降低了MBN含量。增温第2年,土壤中有效磷、NH_4~+和MBP含量显著下降;短期增温虽然对土壤全N/P,有效N/P的影响不显著,但是增温使铵态氮/硝态亚硝态氮(NH_4~+/(NO_3~-+NO_2~-))显著降低;此外,增温显著降低了MBN/MBP,缓解了微生物对磷的限制。相关性分析表明,耦合作用不仅受N和P之间相互作用的影响,也受土壤温度、水分含量等其他因素的影响。研究表明,短期增温并未对中亚热带杉木人工幼林土壤氮磷耦合作用产生显著影响,但增温后降低了有效氮、有效磷的含量。因此,在未来全球变暖背景下,研究结果为中亚热带森林生态系统的的健康发展和科学管理提供重要的理论依据。     

Association between polymorphisms in the promoter region of interleukin-10 and susceptibility to inflammatory bowel disease

The aim of this study was to assess the association of polymorphisms in the promoter region of the IL-10 gene with the risk of inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Fifteen studies (3,693 cases and 4,574 controls) were included in a meta-analysis of association between IL-10 ?1082G/A, ?819C/T and ?592C/A polymorphisms, and IBD, CD and UC using allele contrast and the recessive, dominant, and additive models. Hardy–Weinberg equilibrium was confirmed for each study. Heterogeneity and study quality were investigated using stratification analyses and sensitivity analyses. Polymorphism ?1082G/A showed significant association with CD, with odds ratios (ORs) for the GG + GA genotype and GG versus AA genotype of 1.278 (1.004–1.627) and 1.238 (1.027–1.492) in all subjects. Significant associations were found in the Caucasian subgroup using the allele contrast, dominant, and additive models. C-allele carriers of the ?819C/T polymorphism were at increased risk of IBD (OR 1.093, 95 % CI 1.004–1.190). Association with the ?819C/T polymorphism was also found in Caucasians with CD (C vs. T: OR 1.104, 95 % CI 1.010–1.206; CC + CT vs. TT: OR 1.328, 95 % CI 1.006–1.754; CC vs. TT: OR 1.339, 95 % CI 1.008–1.778), and with UC (CC vs. CT + TT: OR 1.188, 95 % CI 1.019–1.385). No significant association was found between the ?592C/A polymorphism and IBD, CD or UC. In conclusion, the meta-analysis demonstrated clear association between the IL-10 polymorphisms ?1082G/A and ?819C/T and the risk of IBD.     

日本血吸虫中国株次黄嘌呤鸟嘌呤磷酸核糖转移酶的克隆、表达及其免疫保护性研究

根据基因库中日本血吸虫次黄嘌呤鸟嘌呤磷酸核糖转移酶 (HGPRT) EST (BU803192) 以及日本血吸虫成虫cDNA文库载体λgt11多克隆位点邻近核苷酸序列设计引物,以日本血吸虫成虫cDNA文库为模板,采用锚式PCR对SjHGPRT基因不完整的3′端和5′端进行扩增、测序,用电子软件拼接,获得SjHGPRT全长cDNA (1 270 bp),经序列分析,推断该片段含有编码SjHGPRT基因的完整阅读框,其编码基因与曼氏血吸虫次黄嘌呤鸟嘌呤磷酸核糖转移酶 (SmHGPRT) 全长编码基因碱基一致性为82%,其理论推导的氨基酸组成与曼氏血吸虫次黄嘌呤鸟嘌呤磷酸核糖转移酶的一致性约为83%. 将其编码基因克隆到表达载体pQE30上,在大肠杆菌M15中获得准确、高效表达,表达产物分子质量约为28 ku. 用日本血吸虫成虫抗原免疫血清对表达产物进行蛋白质印迹检测,在预测位置上出现明显的识别条带. 重组蛋白动物免疫保护性结果显示：在虫荷、每克肝卵、每克粪卵和雌子宫内卵数方面,疫苗组与对照组比较差异均具有显著性 (P < 0.05,P < 0.01). 结果表明,日本血吸虫次黄嘌呤鸟嘌呤磷酸核糖转移酶 (SjHGPRT) 全长cDNA成功克隆并在大肠菌中得到表达,表达产物具有良好的抗原性和动物免疫保护效果,是一种潜在的具有部分免疫保护性的抗血吸虫病疫苗候选分子.     

Non‐dormant Axillary Bud 1 regulates axillary bud outgrowth in sorghum

Tillering contributes to grain yield and plant architecture and therefore is an agronomically important trait in sorghum (Sorghum bicolor). Here, we identified and functionally characterized a mutant of the Non‐dormant Axillary Bud 1 (NAB1) gene from an ethyl methanesulfonate‐mutagenized sorghum population. The nab1 mutants have increased tillering and reduced plant height. Map‐based cloning revealed that NAB1 encodes a carotenoid‐cleavage dioxygenase 7 (CCD7) orthologous to rice (Oryza sativa) HIGH‐TILLERING DWARF1/DWARF17 and Arabidopsis thaliana MORE AXILLARY BRANCHING 3. NAB1 is primarily expressed in axillary nodes and tiller bases and NAB1 localizes to chloroplasts. The nab1 mutation causes outgrowth of basal axillary buds; removing these non‐dormant basal axillary buds restored the wild‐type phenotype. The tillering of nab1 plants was completely suppressed by exogenous application of the synthetic strigolactone analog GR24. Moreover, the nab1 plants had no detectable strigolactones and displayed stronger polar auxin transport than wild‐type plants. Finally, RNA‐seq showed that the expression of genes involved in multiple processes, including auxin‐related genes, was significantly altered in nab1. These results suggest that NAB1 functions in strigolactone biosynthesis and the regulation of shoot branching via an interaction with auxin transport.     

社会竞争失败病因学的抑郁症树鼩模型

抑郁症是一种常见精神疾病,主要表现为持续两周以上的情绪低落。世界卫生组织预测在2030年抑郁症的疾病负担将高居所有疾病、伤残总负担的榜首。抑郁症面临三大难题:1)发病机理不完全清楚,因而缺乏有效的预测预防途径和生物学诊断;2)现有单胺类抗抑郁症药物起效慢,也可能导致患者自杀风险增加;3)缺乏副作用小的非单胺类快速起效抗抑郁症药物。针对这三大难题,长期以来,应用抑郁症啮齿类模型的众多研究并未取得实质性进展,至少部分因素归咎于啮齿类与人类大脑功能的极大种属差异。树鼩是灵长类近亲,具有更接近于人类的大脑功能。本文针对抑郁症发病机理假说、临床表象和抗抑郁症药物疗效等内容,综述了社会竞争失败病因学的抑郁症树鼩模型可能会具有更好的疾病同源性、表象一致性和药物预见性。这一被长期忽视的抑郁症树鼩模型尽管还需要进一步完善,但对其进一步深入研究可能为解决抑郁症的三大难题提供了一条新途径。     

Synthesis,evaluation and CoMFA/CoMSIA study of nitrofuranyl methyl N-heterocycles as novel antitubercular agents

A series of novel nitrofuranyl methyl N-heterocycles based on the structure of IIIM-MCD-211 were designed and synthesized. Compounds 6d, 8b and 12a show excellent activity against MTB H37Rv strain (MIC: 0.031–0.062?μg/mL) roughly comparable to INH and IIIM-MCD-211. In addition, a three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed on the above mentioned chemical series employing comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques. The developed CoMFA and CoMSIA models display high external predictability (r²_pred of 0.954 and 0.935, respectively) and good statistical robustness. More importantly, the newly designed compounds 16a and 16b (MIC: <0.016?μg/mL) based on the two models, as expected, were found to be more active than 12a and IIIM-MCD-21. Design and synthesis of more potent nitrofuranyl methyl N-heterocycles as anti-TB agents are currently in progress.     

Predictive value of circulating miR-328 and miR-134 for acute myocardial infarction

MicroRNA (miRNAs) is demonstrated to be present in the blood of humans and has been increasingly suggested as a novel biomarker for various pathological processes in the heart, including myocardial infarction, myocardial remodeling and progression to heart failure. In this study, we aim to evaluate the diagnostic and prognostic value of circulating miR-328 and miR-134 in patients with acute myocardial infarction (AMI). Circulating levels of miR-328 and miR-134 were detected by quantitative real-time PCR in plasma samples from 359 AMI patients and 30 healthy volunteers. Concentrations of high-sensitivity cardiac troponin T (hs-cTnT) were measured using electrochemiluminescence-based methods. MiRNAs were assessed for discrimination of a clinical diagnosis of AMI and for association with primary clinical endpoint defined as a composite of cardiogenic death and development of heart failure within 6 months after infarction. Results showed that levels of plasma miR-328 and miR-134 were significantly higher in AMI patients than in healthy controls. Receiver operating characteristic curve analyses showed significant diagnostic value of miR-328 and miR-134 for AMI. However, neither of them was superior to hs-cTnT for the diagnosis. Additionally, increased miRNA levels were strongly associated with increased risk of mortality or heart failure within 6 months for miR-328 (OR 7.35, 95 % confidence interval 1.07–17.83, P < 0.001) and miR-134 (OR 2.28, 95 % confidence interval 1.03–11.32 P < 0.001). In conclusion, circulating miR-328 and miR-134 could be potential indicators for AMI, and the miRNA levels are associated with increased risk of mortality or development of heart failure.