转录调节因子σ~(38)介导铜绿假单胞菌绿脓菌素合成代谢调控

【目的】为了进一步鉴定铜绿假单胞菌转录调控因子σ~(38)对2个拷贝吩嗪合成基因簇(phz A1-G1和phz A2-G2)的具体调控方式并推定介导绿脓菌素合成代谢的可能调控机制。【方法】根据铜绿假单胞菌基因组信息,利用同源重组原理构建rpo S基因缺失突变株Δrpo S以及克隆全长rpo S基因作互补分析;再以单一吩嗪基因簇缺失突变株Δphz1和Δphz2为出发菌株,分别构建rpo S缺失突变株Δrpo Sphz1和rpo S插入突变株Δrpo Sphz2,测定并比较野生株及相关突变株的绿脓菌素合成量,初步推定σ~(38)因子对2个不同吩嗪基因簇表达的调控方式。【结果】在GA培养基中,突变株Δrpo S的绿脓菌素合成量比野生株显著增加;互补分析证实,σ~(38)可使突变株Δrpo S的绿脓菌素降低并接近野生株PAO1水平;与对照株Δphz1相比,突变株Δrpo Sphz1的绿脓菌素合成量因σ~(38)因子缺失而显著减少;而与对照株Δphz2相比,突变株Δrpo Sphz2的绿脓菌素合成量因σ~(38)因子缺失显著增加。【结论】转录调控因子σ~(38)对铜绿假单胞菌绿脓菌素的合成代谢的确具一定的负调控作用;结合已报道的研究结果,初步推定:σ~(38)因子通过负调控吩嗪基因簇phz1,正调控吩嗪基因簇phz2的表达实现对绿脓菌素合成代谢的调控。     

Preclinical Assessment of the Analgesic Pharmacology of NKTR-181 in Rodents

Cellular and Molecular Neurobiology - Pharmacological evaluation of the mu-opioid receptor (MOR) agonist properties of NKTR-181 in rodent models. Graded noxious stimulus intensities were used in...     

无创性颈动脉瞬时减速度波强测定评价左心室舒张功能的研究

目的：探讨无创检测心功能的指标—颈动脉瞬时减速度波强（W2）评价左心室舒张功能的价值。方法：测量40例高血压病患者和43例健康对照者的左、右侧颈总动脉W2,组织多普勒测定二尖瓣环运动速度和血清脑利钠肽前体（N-terminal probrain natriuretic peptide,NT-proBNP）,分析W2与各参数间的相关性。结果：①高血压组W2低于对照组,以左侧明显（1126±996vs1690±1126 mmHg.m/s3,P〈0.01）;②高血压组与对照组比较：E/Em（二尖瓣舒张早期峰值速度/二尖瓣环舒张早期纵向运动峰值速度）增大（9.37±3.32vs7.39±1.83,P〈0.01）,NT-proB-NP升高（94.6±48.5vs45.2±13.8,P〈0.01）;③相关性分析：W2与E/Em负相关（r=-0.46,P〈0.05）,与NT-proBNP负相关（r=-0.21,P〈0.05）。结论：无创性评价血流动力学的新技术指标W2是反映早期左室舒张功能受损的敏感指标。     

A New Model for Predicting Non-Sentinel Lymph Node Status in Chinese Sentinel Lymph Node Positive Breast Cancer Patients

Background

Our goal is to validate the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and Stanford Online Calculator (SOC) for predicting non-sentinel lymph node (NSLN) metastasis in Chinese patients, and develop a new model for better prediction of NSLN metastasis.

Methods

The MSKCC nomogram and SOC were used to calculate the probability of NSLN metastasis in 120 breast cancer patients. Univariate and multivariate analyses were performed to evaluate the relationship between NSLN metastasis and clinicopathologic factors, using the medical records of the first 80 breast cancer patients. A new model predicting NSLN metastasis was developed from the 80 patients.

Results

The MSKCC and SOC predicted NSLN metastasis in a series of 120 patients with an area under the receiver operating characteristic curve (AUC) of 0.688 and 0.734, respectively. For predicted probability cut-off points of 10%, the false-negative (FN) rates of MSKCC and SOC were both 4.4%, and the negative predictive value (NPV) 75.0% and 90.0%, respectively. Tumor size, Kiss-1 expression in positive SLN and size of SLN metastasis were independently associated with NSLN metastasis (p<0.05). A new model (Peking University People''s Hospital, PKUPH) was developed using these three variables. The MSKCC, SOC and PKUPH predicted NSLN metastasis in the second 40 patients from the 120 patients with an AUC of 0.624, 0.679 and 0.795, respectively.

Conclusion

MSKCC nomogram and SOC did not perform as well as their original researches in Chinese patients. As a new predictor, Kiss-1 expression in positive SLN correlated independently with NSLN metastasis strongly. PKUPH model achieved higher accuracy than MSKCC and SOC in predicting NSLN metastasis in Chinese patients.     

Melatonin protects against defects induced by malathion during porcine oocyte maturation

Malathion (MAL) is a common organophosphorus pesticide and affects both animal and human reproduction. However, the mechanisms regarding how MAL affects the mammalian oocyte quality and how to prevent it have not been fully investigated. In this study, we used porcine oocyte as a model and proved that MAL impaired porcine oocyte quality in a dose-dependent manner during maturation. MAL decreased the first polar body extrusion, disrupted spindle assembly and chromosome alignment, impaired cortical granules (CGs) distribution, and increased reactive oxygen species (ROS) level in oocytes. RNA-seq analysis showed that MAL exposure altered the expression of 2,917 genes in the porcine maturated oocytes and most genes were related to ROS, the lipid droplet process, and the energy supplement. Nevertheless, these defects could be remarkably ameliorated by adding melatonin (MLT) into the oocyte maturation medium. MLT increased oocyte maturation rate and decreased the abnormities of spindle assembly, CGs distribution and ROS accumulation in MAL-exposed porcine oocytes. More important, MLT upregulated the expression of genes related to lipid droplet metabolism (PPARγ and PLIN2), decreased lipid droplet size and lipid peroxidation in MAL-exposed porcine oocytes. Finally, we found that MLT increased the blastocysts formation and the cell numbers of blastocysts in MAL-exposed porcine oocytes after parthenogenetic activation, which was mediated by reduction of ROS levels and maintaining lipid droplet metabolism. Taken together, our results revealed that MLT had a protective action against MAL-induced deterioration of porcine oocyte quality.     

The role of microvesicles and its active molecules in regulating cellular biology

Cell‐derived microvesicles are membrane vesicles produced by the outward budding of the plasma membrane and released by almost all types of cells. These have been considered as another mechanism of intercellular communication, because they carry active molecules, such as proteins, lipids and nucleic acids. Furthermore, these are present in circulating fluids, such as blood and urine, and are closely correlated to the progression of pathophysiological conditions in many diseases. Recent studies have revealed that microvesicles have a dual effect of damage and protection of receptor cells. However, the nature of the active molecules involved in this effect remains unclear. The present study mainly emphasized the mechanism of microvesicles and the active molecules mediating the different biological effects of receptor cells by affecting autophagy, apoptosis and inflammation pathways. The effective ways of blocking microvesicles and its active molecules in mediating cell damage when microvesicles exert harmful effects were also discussed.     

江苏省不同农业区土壤线虫群落分布特征

调查了江苏省不同农业区农田土壤线虫群落多样性,分析了土壤线虫数量和群落结构与土壤环境因子的关系,并探讨了土壤线虫对土壤健康的生物指示作用.结果表明： 农田土壤线虫共鉴定出2纲7目19科41属.6个农业区的土壤线虫的密度、群落组成均具有一定的差异性.沿海农业区的线虫数量最多(每100 g干土400条),显著高于徐淮、宁镇扬和沿江农业区(P＜0.05),而沿江农业区的土壤线虫数量最少(每100 g干土232条),这可能是由于土壤质地、年均降雨量和年均气温等因素的差异造成的.地理位置相近的农业区线虫优势属相似.相关性分析结果显示,土壤线虫数量与土壤有机质、全氮、速效氮、速效钾和速效磷均呈显著正相关关系;RDA分析表明,土壤全氮含量、速效磷及pH对线虫群落种属组成影响较大.分析江苏省农田土壤线虫群落空间分布特征,可为农田土壤生态系统健康状况评价提供数据支撑.