MicroRNA-149 Inhibits Proliferation and Cell Cycle Progression through the Targeting of ZBTB2 in Human Gastric Cancer

An increasing body of evidence indicates that miR-149 can both suppress and promote tumor growth depending on the tumor type. However, the role of miR-149 in the progression of gastric cancer (GC) remains unknown. Here we report that miR-149 is a tumor suppressor in human gastric cancer. miR-149 expression is decreased in GC cell lines and clinical specimens in comparison to normal gastric epithelial cell and tissues, respectively. The expression levels of miR-149 also correlate with the differentiation degree of GC cells and tissues. Moreover, ectopic expression of miR-149 in gastric cancer cells inhibits proliferation and cell cycle progression by down-regulating ZBTB2, a potent repressor of the ARF-HDM2-p53-p21 pathway, with a potential binding site for miR-149 in its mRNA''s 3′UTR. It is also found that ZBTB2 expression increases in GC cells and tissues compared to normal gastric epithelial cell and tissues, respectively. Silencing of ZBTB2 leads to suppression of cell growth and cell cycle arrest in G0/G1 phase, indicating that ZBTB2 may act as an oncogene in GC. Furthermore, transfection of miR-149 mimics into gastric cancer cells induces down-regulation of ZBTB2 and HDM2, and up-regulation of ARF, p53, and p21 compared to the controls. In summary, our data suggest that miR-149 functions as a tumor suppressor in human gastric cancer by, at least partially through, targeting ZBTB2.     

一个新型耐热普鲁兰酶的结构与功能

新型普鲁兰酶的研究对于普鲁兰酶制剂的国产化、打破国外垄断具有非常重要的意义。从我国云南腾冲地区轮马热泉的淤泥中分离获得了一株耐热普鲁兰酶产生菌LM 18-11,经16S rDNA序列系统进化树分析,确定该菌为厌氧芽胞杆菌Anoxybacillus属种,并从中克隆获得了耐热普鲁兰酶的编码基因,该酶在55℃-60℃、pH 5.6-6.4的范围内具有最大的反应活性。此外,该酶具有较好的热稳定性,在60℃下处理48 h,仍可保持50%以上的活力;动力学分析该酶的Vmax和Km分别为750 U/mg和1.47 mg/mL,是目前文献报道中比活力最高的耐热普鲁兰酶。同时还对该酶进行了晶体结构分析,结果显示该酶具有?-淀粉酶家族中典型的结构,在N端具有一个特殊的底物结合域,该结构域的缺失导致比活力和底物结合力都有相应降低,Vmax和Km分别为324 U/mg和1.95 mg/mL。同时,将该普鲁兰酶编码基因导入枯草芽胞杆菌中,在P43启动子的控制下,普鲁兰酶基因获得了高效表达,胞外酶活可达42 U/mL,相比初始菌种,表达活力提高40倍以上。研究表明该普鲁兰酶具有很好的应用前景。     

Whole-genome sequencing of matched primary and metastatic hepatocellular carcinomas

Background

To gain biological insights into lung metastases from hepatocellular carcinoma (HCC), we compared the whole-genome sequencing profiles of primary HCC and paired lung metastases.

Methods

We used whole-genome sequencing at 33X-43X coverage to profile somatic mutations in primary HCC (HBV+) and metachronous lung metastases (> 2 years interval).

Results

In total, 5,027-13,961 and 5,275-12,624 somatic single-nucleotide variants (SNVs) were detected in primary HCC and lung metastases, respectively. Generally, 38.88-78.49% of SNVs detected in metastases were present in primary tumors. We identified 65–221 structural variations (SVs) in primary tumors and 60–232 SVs in metastases. Comparison of these SVs shows very similar and largely overlapped mutated segments between primary and metastatic tumors. Copy number alterations between primary and metastatic pairs were also found to be closely related. Together, these preservations in genomic profiles from liver primary tumors to metachronous lung metastases indicate that the genomic features during tumorigenesis may be retained during metastasis.

Conclusions

We found very similar genomic alterations between primary and metastatic tumors, with a few mutations found specifically in lung metastases, which may explain the clinical observation that both primary and metastatic tumors are usually sensitive or resistant to the same systemic treatments.     

Enzymatic liquefaction and saccharification of pretreated corn stover at high-solids concentrations in a horizontal rotating bioreactor

A self-designed horizontal rotating bioreactor (HRR) was applied for enzymatic hydrolysis of pretreated corn stover to improve the process economics of ethanol production. The mixing principle was based on gravity and free fall employed with tank-rotating. The liquefaction performances using the HRR and the vertical stirred-tank reactor (VSTR) with a helical impeller were compared and analyzed by measuring rheological properties of the slurry. During the enzymatic hydrolysis, viscosity decreased dramatically in the initial phase for both bioreactors and more pronouncedly for the HRR. Rheological parameters fitted to the power law showed that shear thinning properties of the slurry weakened during the reaction. The glucose concentration was used to define the efficiency of the saccharification reaction. The HRR also proved to be more efficient for glucose release with both the constant and fed-batch substrate addition modes. Liquefaction and saccharification at 25 % w/w dry matter (DM) and enzyme loading of 7 FPU/g DM resulted in the optimal glucose concentration of 86 g/kg. Results revealed a decrease in cellulose conversion at increasing initial DM, which was slighter in the HRR compared with that in the VSTR.     

南四湖区农田土壤有机质和微量元素空间分布特征及影响因素

基于地统计学和GIS技术相结合的方法,研究了南四湖区农田土壤有机质和微量元素的空间分布特征及其影响因素。结果表明,土壤有机质和微量元素均属中等变异程度,除硼符合正态分布外,其余土壤属性均符合对数正态分布。结构分析表明,除硼为纯块金效应外,土壤有机质和其它微量元素空间自相关性较强,其中结构性因素起主导作用。克里格插值结果表明,土壤有机质分布总体趋势为由北向南逐渐降低,锰、铜、锌分布总体趋势为中部高,南北两端低。影响因素分析表明,土壤类型、耕层质地、坡度、土地利用类型和地貌类型对土壤有机质均有显著影响。土壤类型主要是由于成土母质的差异影响土壤有机质的高低与分布,随质地由砂变粘、坡度由低变高,土壤有机质含量逐步升高,田间管理水平的差异是造成不同土地利用类型下土壤有机质含量差异的主要原因。微量元素中,除硼不受影响外,铁、锰、铜和锌与土壤类型、耕层质地、坡度、土地利用类型和地貌类型密切相关。     

斑块生境中食果鸟类对南方红豆杉种子的取食和传播

生境斑块化对食果鸟类的移动行为产生影响,进而影响其对植物种子的传播格局和效率。南方红豆杉(Taxus chinensis var.mairei)是我国一级保护植物,在南方山区多因人为干扰而呈斑块状分布。2011年,2012年10月底到12月中,以分布于福建梅花山国家级自然保护区红豆杉生态园中南方红豆杉种群为对象,研究斑块生境中鸟类对南方红豆杉种子的取食和传播行为,并评估专性鸟类和泛性鸟类的传播效率。结果发现:南方红豆杉源斑块共吸引22种食果鸟类取食红豆杉种子,并与13种鸟类形成了种子传播关系。不同年间,黑短脚鹎(Hypsipetes leucocephalus)都是植物的主要传播鸟类,而其他鸟类传播者种类具有一定的年间变化。生境斑块化导致专性鸟类黑短脚鹎和泛性鸟类红嘴蓝鹊(Urocissa erythrorhyncha)种子传播效率差异。与红嘴蓝鹊相比,黑短脚鹎飞行的平均距离较短((16.3±11.0)m,Mean±SD,n=125),传播距离相对较近;且它们取食后偏好在源斑块中活动,喜栖息在同种成树、甜楮(Castanopsis eyrei)及其他阔叶树等栖树上。红嘴蓝鹊取食后常在斑块间移动,常停歇在同种成树和毛竹(Phyllostachys heterocycla)上,传播距离相对较远((24.9±20.0)m,Mean±SD,n=95)。空间一致性结果表明,黑短脚鹎移动距离对幼苗更新距离的空间一致性程度高;而红嘴蓝鹊偏好生境与幼苗更新生境一致性程度高。结果表明,斑块生境中植物能与专性鸟类、泛性鸟类之间形成种子传播互惠关系,且种子传播效率受到专性鸟类和泛性鸟类传播距离和传播生境的影响。     

Hydrogen Sulfide Prolongs Postharvest Storage of Fresh-Cut Pears (Pyrus pyrifolia) by Alleviation of Oxidative Damage and Inhibition of Fungal Growth

Hydrogen sulfide (H₂S) has proved to be a multifunctional signaling molecule in plants and animals. Here, we investigated the role of H₂S in the decay of fresh-cut pears (Pyrus pyrifolia). H₂S gas released by sodium hydrosulfide (NaHS) prolonged the shelf life of fresh-cut pear slices in a dose-dependent manner. Moreover, H₂S maintained higher levels of reducing sugar and soluble protein in pear slices. H₂S significantly reduced the accumulation of hydrogen peroxide (H₂O₂), superoxide radicals (•O₂ ⁻) and malondialdehyde (MDA). Further investigation showed that H₂S fumigation up-regulated the activities of antioxidant enzymes ascorbate peroxidase (APX), catalase (CAT), and guaiacol peroxidase (POD), while it down-regulated those of lipoxygenase (LOX), phenylalanine ammonia lyase (PAL) and polyphenol oxidase (PPO). Furthermore, H₂S fumigation effectively inhibited the growth of two fungal pathogens of pear, Aspergillus niger and Penicillium expansum, suggesting that H₂S can be developed as an effective fungicide for postharvest storage. The present study implies that H₂S is involved in prolonging postharvest storage of pears by acting as an antioxidant and fungicide.     

受白粉菌诱导大麦抗感等基因系蛋白质变化的双向电泳分析

分别对接种与否的大麦抗—感白粉病等基因系—叶期幼苗取材进行蛋白质双向电泳分析。结果表明,病原的侵入使抗—感两系在30Kd以下的低分子量区域的蛋白质发生了明显变化。接种48小时之后,抗病系在pH5.5、6.0、6.8及8.8附近出现了对照中所没有的蛋白质,而在pH6.0和8.8附近的蛋白质则较对照有减小的趋势;感病系在pH6.0附近蛋白质明显增多,在pH8.8处不仅在量上有大幅度提高,而且种类也有增加。结果还表明,抗—感系间在未接种的情况下双向电泳图谱也有差异,接种之后由于感病系在pH8.8处蛋白质的特异性合成,使抗—感两系间的差异缩小。     

Kruppel‐like factor 4 improves obesity‐related nephropathy through increasing mitochondrial biogenesis and activities

Obesity is positively linked to multiple metabolic complications including renal diseases. Several studies have demonstrated Kruppel‐like factor 4 (KLF4) participated in renal dysfunction and structural disorders in acute kidney injuries, but whether it affected the process of chronic kidney diseases was unknown. Therefore, present study was to disclose the role of renal KLF4 in dietary‐induced renal injuries and underlying mechanisms in obesity. Through utilizing high‐fat diet‐fed mice and human renal biopsies, we provided the physiological roles of KLF4 in protecting against obesity‐related nephropathy. Decreased levels of renal KLF4 were positively correlated with dietary‐induced renal dysfunction, including increased levels of creatinine and blood urea nitrogen. Overexpression of renal KLF4 suppressed inflammatory response in palmitic acid‐treated mouse endothelial cells. Furthermore, overexpressed KLF4 also attenuated dietary‐induced renal functional disorders, abnormal structural remodelling and inflammation. Mechanistically, KLF4 maintained renal mitochondrial biogenesis and activities to combat obesity‐induced mitochondrial dysfunction. In clinical renal biopsies and plasma, the renal Klf4 level was negatively associated with circulating levels of creatinine but positively associated with renal creatinine clearance. In conclusions, the present findings firstly supported that renal KLF4 played an important role in combating obesity‐related nephropathy, and KLF4/mitochondrial function partially determined the energy homeostasis in chronic kidney diseases.