Molecular Mechanisms and Tumor Biological Aspects of 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells

5-Fluorouracil (5-FU) is a cornerstone drug used in the treatment of colorectal cancer (CRC). However, the development of resistance to 5-FU and its analogs remain an unsolved problem in CRC treatment. In this study, we investigated the molecular mechanisms and tumor biological aspects of 5-FU resistance in CRC HCT116 cells. We established an acquired 5-FU-resistant cell line, HCT116R^F10. HCT116R^F10 cells were cross-resistant to the 5-FU analog, fluorodeoxyuridine. In contrast, HCT116R^F10 cells were collaterally sensitive to SN-38 and CDDP compared with the parental HCT16 cells. Whole-exome sequencing revealed that a cluster of genes associated with the 5-FU metabolic pathway were not significantly mutated in HCT116 or HCT116R^F10 cells. Interestingly, HCT116R^F10 cells were regulated by the function of thymidylate synthase (TS), a 5-FU active metabolite 5-fluorodeoxyuridine monophosphate (FdUMP) inhibiting enzyme. Half of the TS was in an active form, whereas the other half was in an inactive form. This finding indicates that 5-FU-resistant cells exhibited increased TS expression, and the TS enzyme is used to trap FdUMP, resulting in resistance to 5-FU and its analogs.     

MiR-10a in Pancreatic Juice as a Biomarker for Invasive Intraductal Papillary Mucinous Neoplasm by miRNA Sequencing

New biomarkers are needed to further stratify the risk of malignancy in intraductal papillary mucinous neoplasm (IPMN). Although microRNAs (miRNAs) are expected to be stable biomarkers, they can vary owing to a lack of definite internal controls. To identify universal biomarkers for invasive IPMN, we performed miRNA sequencing using tumor-normal paired samples. A total of 19 resected tissues and 13 pancreatic juice samples from 32 IPMN patients were analyzed for miRNA expression by next-generation sequencing with a two-step normalization of miRNA sequence data. The miRNAs involved in IPMN associated with invasive carcinoma were identified from this tissue analysis and further verified with the pancreatic juice samples. From the tumor-normal paired tissue analysis of the expression levels of 2792 miRNAs, 20 upregulated and 17 downregulated miRNAs were identified. In IPMN associated with invasive carcinoma (INV), miR-10a-5p and miR-221-3p were upregulated and miR-148a-3p was downregulated when compared with noninvasive IPMN. When these findings were further validated with pancreatic juice samples, miR-10a-5p was found to be elevated in INV (p = 0.002). Therefore, three differentially expressed miRNAs were identified in tissues with INV, and the expression of miR-10a-5p was also elevated in pancreatic juice samples with INV. MiR-10a-5p is a promising additional biomarker for invasive IPMN.     

A Degeneration Gradient of Poplar Trees Contributes to the Taxonomic,Functional, and Resistome Diversity of Bacterial Communities in Rhizosphere Soils

Bacterial communities associated with roots influence the health and nutrition of the host plant. However, the microbiome discrepancy are not well understood under different healthy conditions. Here, we tested the hypothesis that rhizosphere soil microbial diversity and function varies along a degeneration gradient of poplar, with a focus on plant growth promoting bacteria (PGPB) and antibiotic resistance genes. Comprehensive metagenomic analysis including taxonomic investigation, functional detection, and ARG (antibiotics resistance genes) annotation revealed that available potassium (AK) was correlated with microbial diversity and function. We proposed several microbes, Bradyrhizobium, Sphingomonas, Mesorhizobium, Nocardioides, Variovorax, Gemmatimonadetes, Rhizobacter, Pedosphaera, Candidatus Solibacter, Acidobacterium, and Phenylobacterium, as candidates to reflect the soil fertility and the plant health. The highest abundance of multidrug resistance genes and the four mainly microbial resistance mechanisms (antibiotic efflux, antibiotic target protection, antibiotic target alteration, and antibiotic target replacement) in healthy poplar rhizosphere, corroborated the relationship between soil fertility and microbial activity. This result suggested that healthy rhizosphere soil harbored microbes with a higher capacity and had more complex microbial interaction network to promote plant growing and reduce intracellular levels of antibiotics. Our findings suggested a correlation between the plant degeneration gradient and bacterial communities, and provided insight into the role of high-turnover microbial communities as well as potential PGPB as real-time indicators of forestry soil quality, and demonstrated the inner interaction contributed by the bacterial communities.     

SBR法处理柠檬酸废水pH变化规律研究

探索了用SBR法处理柠檬酸废水过程中pH的变化规律。研究了柠檬酸废水处理过程中pH变化与COD处理效率的关系，研究目的在于利用易于检测的水质参数为实现SBR处理过程的自动监测和调控作基础试验研究。     

SBR反应器中反硝化条件下去除苯酚工艺

基于异养反硝化原理,在序批式间歇反应器(SBR)中对反硝化同时降解苯酚的菌种进行了149 d的驯化,驯化通过逐步提高进水中苯酚和NO3--N的浓度进行.驯化结束后,进水苯酚质量浓度达到360 mg/L,葡萄糖质量浓度达到100 mg/L,NO3--N质量浓度达到240 mg/L,水力停留时间6 h,苯酚和NO3--N去除率均大于98%.反应器运行结果表明:进水苯酚质量浓度低于720 mg/L时,SBR反应器运行稳定;高浓度NO2--N(＞60 mg/L)可以严重影响微生物对苯酚以及NO3--N的去除能力,同时反应器中20.5%～23.5%的COD可被用于微生物的细胞合成.     

UASB-SBR工艺处理城市生活污水的研究

研究了UASB工艺处理城市生活污水的可行性，通过UASB与SBR组合工艺的运行实验，得出在水力停留时间3h时，COD去除率为61．67％-82．32％，出水COD达到国家污水排放二级标准。在氮磷去除效果不佳的情况下，采用SBR工艺处理后，其出水COD、SS、氮、磷等指标均达到国家污水一级排放标准。     

Modeling and solving mixed-model assembly line balancing problem with setups. Part I: A mixed integer linear programming model

This paper is the first one of the two papers entitled “modeling and solving mixed-model assembly line balancing problem with setups”, which has the aim of developing the mathematical programming formulation of the problem and solving it with a hybrid meta-heuristic approach. In this current part, a mixed-integer linear mathematical programming (MILP) model for mixed-model assembly line balancing problem with setups is developed. The proposed MILP model considers some particular features of the real world problems such as parallel workstations, zoning constraints, and sequence dependent setup times between tasks, which is an actual framework in assembly line balancing problems. The main endeavor of Part-I is to formulate the sequence dependent setup times between tasks in type-I mixed-model assembly line balancing problem. The proposed model considers the setups between the tasks of the same model and the setups because of the model switches in any workstation. The capability of our MILP is tested through a set of computational experiments. Part-II tackles the problem with a multiple colony hybrid bees algorithm. A set of computational experiments is also carried out for the proposed approach in Part-II.     

Klebsieila sp．601细菌漆酶的鉴定及性质

从森林树木根部土壤中分离得到一株具有2，6-二甲氧基酚（DMP）和2，2＇-连氮基-双（3-乙基苯丙噻唑啉-6磺酸（ABTS）氧化活性的细菌。Cu^2＋、Ca^2＋、Mn^2＋、Fe^2＋和Mg^2＋可诱导细菌表达活性的胞质可溶性单体酶蛋白。该酶进行DMP或ABTS氧化时需要铜离子的协助，在pH5．0～7．5范围内氧化DMP，在pH4．0～4．5范围内氧化ABTS，但不能氧化酪氨酸。SDS-PAGE估测酶蛋白分子量大约为55kD。经60℃处理4h或pH10条件下透析20h仍能保持酶活性。16S rDNA序列分析结合常规细菌形态学分析，表明该细菌属于克雷伯氏菌（Klebsiella）属，并命名为Klebsiella sp．60l。这是首例报道Klebsiella细菌菌株具有漆酶活性。