Microsatellite instability in gastric cancer: molecular bases,clinical perspectives,and new treatment approaches

Gastric cancer is one of the most aggressive malignancies, with limited treatment options in both locally advanced and metastatic setting, resulting in poor prognosis. Based on genomic characterization, stomach tumour has recently been described as a heterogeneous disease composed by different subtypes, each of them with peculiar molecular aspects and specific clinical behaviour. With an incidence of 22% among all western gastric tumour cases, stomach cancer with microsatellite instability was identified as one of these subgroups. Retrospective studies and limited prospective trials reported differences between gastric cancers with microsatellite stability and those with instability, mainly concerning clinical and pathological features, but also in regard to immunological microenvironment, correlation with prognostic value, and responses to treatment. In particular, gastric cancer with microsatellite instability constitutes a small but relevant subgroup associated with older age, female sex, distal stomach location, and lower number of lymph-node metastases. Emerging data attribute to microsatellite instability status a favourable prognostic meaning, whereas the poor outcomes reported after perioperative chemotherapy administration suggest a detrimental role of cytotoxic drugs in this gastric cancer subgroup. The strong immunogenicity and the widespread expression of immune-checkpoint ligands make microsatellite instability subtype more vulnerable to immunotherapeutic approach, e.g., with anti-PD-L1 and anti-CTLA4 antibodies. Since gastric cancer with microsatellite instability shows specific features and clinical behaviour not overlapping with microsatellite stable disease, microsatellite instability test might be suitable for inclusion in a diagnostic setting for all tumour stages to guarantee the most targeted and effective treatment to every patient.     

Maternal eating behavior is a major synchronizer of fetal and postnatal peripheral clocks in mice

Most living organisms show circadian rhythms in physiology and behavior. These oscillations are generated by endogenous circadian clocks, present in virtually all cells where they control key biological processes. To study peripheral clocks in vivo, we developed an original model, the Rev-Luc mouse to follow noninvasively and longitudinally Rev-Luc oscillations in peripheral clocks using in vivo bioluminescence imaging. We found in vitro and in vivo a robust diurnal rhythm of Rev-Luc, mainly in liver, intestine, kidney and adipose tissues. We further confirmed in vivo that Rev-Luc peripheral tissues are food-entrainable oscillators, not affected by age or sex. These data strongly support the relevance of the Rev-Luc model for circadian studies, especially to investigate in vivo the establishment and the entrainment of the rhythm throughout ontogenesis. We then showed that Rev-Luc expression develops dynamically and gradually, both in amplitude and in phase, during fetal and postnatal development. We also demonstrate for the first time that the immature peripheral circadian system of offspring in utero is mainly entrained by maternal cues from feeding regimen. The prenatal entrainment will also differentially determine the Rev-Luc expression in pups before weaning underlining the importance of the maternal chrononutrition on the circadian system entrainment of the offspring.     

浅谈功率因数的补偿及其应用

根据我国当前电力系统运行情况，对电网无功功率补偿的必要性及通用补偿方法及其装置进行了具体阐述。     

我国巨型机发展概述

系统地总结和介绍了我国高性能计算机，包括“银河”系列巨型机、“曙光”系列巨型机、“神威”系列巨型机、“深腾”系列巨型机以及“深超”系列巨型机的开发研制以及应用情况。     

建筑物地基处理的设计与施工探讨

以具体工程为例，介绍了建筑物地基处理的设计、施工中遵循的原则，施工中遇到特殊情况时采取的处理方法和必要的检测方法，对几种桩基的设计要求、施工工艺及过程、质量控制等情况进行了简单阐述。     

顶凌覆盖节水增产技术研究

通过1998年、2000年的试验研究，系统分析了顶凌覆盖技术在高寒区节水增温保温、增产增收的机理及其应用效果。提出该技术可以缓解低温干旱特别是春旱对农业生产的困扰，是一项可以抗旱保春播增产增收的实用技术，在高寒地区具有较高的推广价值。     

The influence of chronic nicotine treatment on stress-induced gastric ulceration and emptying rate in rats.

Ten-day treatment with nicotine (5, 25 or 50 micrograms/ml drinking water) dose-dependently intensified gastric ulceration induced by cold-restraint, and emptying rate. Stomach contractions produced by graded doses of bethanechol i.v. were elevated further by nicotine treatment. It is suggested that chronic nicotine administration produces hypersensitivity of the gastric muscarinic receptors; stomach hypermotility contributes to the ulcer-worsening action of the alkaloid.     

森林生物技术走出实验室举步艰难

新的、高密度树木种植正在给林业生物技术带来迅速的变化。但是如果不能克服生态风险和经济障碍．这些新的方法或许永远也无法使用——     

The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast

The autosomal recessive disorder Shwachman-Diamond syndrome, characterized by bone marrow failure and leukemia predisposition, is caused by deficiency of the highly conserved Shwachman-Bodian-Diamond syndrome (SBDS) protein. Here, we identify the function of the yeast SBDS ortholog Sdo1, showing that it is critical for the release and recycling of the nucleolar shuttling factor Tif6 from pre-60S ribosomes, a key step in 60S maturation and translational activation of ribosomes. Using genome-wide synthetic genetic array mapping, we identified multiple TIF6 gain-of-function alleles that suppressed the pre-60S nuclear export defects and cytoplasmic mislocalization of Tif6 observed in sdo1Delta cells. Sdo1 appears to function within a pathway containing elongation factor-like 1, and together they control translational activation of ribosomes. Thus, our data link defective late 60S ribosomal subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition.