Impact of Diffusion Barriers to Small Cytotoxic Molecules on the Efficacy of Immunotherapy in Breast Cancer

Molecular-focused cancer therapies, e.g., molecularly targeted therapy and immunotherapy, so far demonstrate only limited efficacy in cancer patients. We hypothesize that underestimating the role of biophysical factors that impact the delivery of drugs or cytotoxic cells to the target sites (for associated preferential cytotoxicity or cell signaling modulation) may be responsible for the poor clinical outcome. Therefore, instead of focusing exclusively on the investigation of molecular mechanisms in cancer cells, convection-diffusion of cytotoxic molecules and migration of cancer-killing cells within tumor tissue should be taken into account to improve therapeutic effectiveness. To test this hypothesis, we have developed a mathematical model of the interstitial diffusion and uptake of small cytotoxic molecules secreted by T-cells, which is capable of predicting breast cancer growth inhibition as measured both in vitro and in vivo. Our analysis shows that diffusion barriers of cytotoxic molecules conspire with γδ T-cell scarcity in tissue to limit the inhibitory effects of γδ T-cells on cancer cells. This may increase the necessary ratios of γδ T-cells to cancer cells within tissue to unrealistic values for having an intended therapeutic effect, and decrease the effectiveness of the immunotherapeutic treatment.     

卫星影象目视解译方法在湖区植被制图中的应用——以湖南洞庭湖区水域、洲滩植被图为例

植被(包括天然植被、人工植被)作为一种可更新资源始终是遥感应用专家们热心研究的课题。植被分类是植被研究的重要方面之一。利用卫星影象进行植被分类,国内外学者都进行了许多有意义的探索。本文以洞庭湖水域、洲滩植被为对象,试用卫星影象进行植被分类。本文从植被与环境相互依赖关系及在影象上的综合反映出发,提出了影象的景观生态学分析方法;即把影象上色调、形态特征与群落生态学规律结合起来分析,并以此作为植被目视解译的方法。在此基础上,将洞庭湖水域、洲滩划分成五个景观生态模型,17个基本植被类型。     

Screening and Mutagenesis of Aspergillus niger for the Improvement of Glucose-6-Phosphate Dehydrogenase Production

The Aspergillus niger strain ZBY-7 was selected as the original strain of glucose-6-phosphate dehydrogenase production. After mutagenesis of the strain by means of UV irradiation and nitrosoguanidine, mutants of Aspergillus niger resistant to a certain metabolic inhibitor were obtained. Five of the mutants showed increased glucose-6-phosphate dehydrogenase production. The mutant resistant to antimycin A (Aspergillus niger AM-23) produced the highest level of glucose-6-phosphate dehydrogenase (695.9% of that produced by the original strain).     

Generation and analysis of expressed sequence tags for microsatellite marker development in Calamus simplicifolius C. F. Wei

Rattans serve as an important source of raw non-wood materials for furniture and handicraft industries worldwide. However, their genomic sequence information in public databases is very limited. In this study, a set of 2,528 good-quality expressed sequence tags (ESTs) were generated from a full-length cDNA library constructed previously with root, stem and male inflorescence tissues of Calamus simplicifolius C. F. Wei, a rattan species native to Hainan Island, China. The ESTs were assembled into 1,588 unigenes, including 1,221 singletons and 367 contigs. BlastX searches against the GenBank non-redundant protein database revealed that 1,248 (78.6 %) unigenes had at least one significant match (E ≤ 10^?5). The gene ontology functional classification assigned 991, 669 and 977 of the unigenes to the cellular component, molecular function and biological process categories, respectively. A total of 71 simple sequence repeat (SSR) loci were developed among these ESTs, including 65 polymorphic across 19 rattan species representing three genera. High levels of cross-species/genus transferability were observed for the EST-SSRs. For the polymorphic EST-SSR markers, the number of alleles per locus and polymorphic information content ranged from 2 to 25 (mean 11.1) and from 0.135 to 0.949 (mean 0.695), respectively. The EST sequences and the EST-SSR primers have been deposited in GenBank databases of EST (IDs JK838364–40891) and Probe (IDs Pr16718978–9048, to be assigned).     

稻—萍—鱼系统中红萍氮素吸收利用及有效性研究

本文报道以红萍为饵料,鱼类对红萍氮素消化吸收、转化情况。试验结果表明:草鱼和尼罗罗非鱼对红萍氮素的消化和吸收率约为60％,其中30％红萍氮素转化为鱼体动物蛋白,另外约30％氮素排出体外。在田间条件下,尼罗罗非鱼摄食红萍,每季平均增长率约为41—40％。稻田养鱼,以萍喂鱼,鱼粪肥田,萍体氮素得以吸收利用,效益明显。在稻萍鱼体系中,当季红萍氮素的总利用率可达45—50％,而红萍单作肥料处理其利用率仅为30—36％,第二季作物对红萍残留氮素回收率可达7.83—9.64％,比红萍单作肥料处理高3.33—4.11％。第二季残效明显优于红萍压施处理,晚季稻谷产量的增产率可达13—25％,比压施红萍作肥料处理高7—8％。     

鳗鱼肌肉的氨基酸及营养价值

通过对优质食用鱼类—鳗鱼肌肉的氨基酸进行测定证实,鳗鱼较之其它鱼类是一种营养价值更高、滋味更鲜美的鱼类。并且,根据结果氨基酸组成比例,可为鳗鱼的人工饲养等方面的研究提供理论依据。     

Effects of the Interactions between Dust Exposure and Genetic Polymorphisms in Nalp3, Caspase-1, and IL-1β on the Risk of Silicosis: A Case-Control Study

Objectives

To evaluate the effects of the interactions between polymorphisms in Nalp3, caspase-1, and interleukin(IL)-1β genes and occupational dust exposure on the risk of silicosis.

Methods

We conducted a population-based case-control study in a large iron mine in China. Between January 2006 and December 2009, we identified 179 patients with silicosis to evaluate as cases and 201 individuals without silicosis to evaluate as controls. We estimated cumulative dust exposure (CDE) for all subjects and we genotyped polymorphisms in Nalp3, caspase-1, and IL-1β genes. We estimated odds ratios(ORs), 95% confidence intervals(95%CIs), and p-values using logistic regression models adjusted for selected confounders.

Results

After adjusting for age, smoking status, and CDE, subjects with the CT genotype of Ex4-849C>T in Nalp3 and the GA genotype of Ex2+37G>A in caspase-1 had increased risks of silicosis (adjusted ORs[95%CIs] = 2.40 [1.12–5.12] and 3.62 [1.63–8.02], respectively). Among subjects younger than 70 years old, those with the CC genotype of IVS8-7652A>C in Nalp3 had a lower risk of silicosis than those with other genotypes (adjusted OR[95%CI] = 0.24[0.06–0.88]). Among subjects aged 70 years and older, those with the CT genotype of Ex4-849C>T in Nalp3 and those with the GA genotype of Ex2+37G>A in caspase-1 had a higher risk of silicosis than those with other genotypes (adjusted ORs [95%CI] = 2.52[1.04–6.12] and 5.19[1.88–14.35], respectively). Among subjects with CDE greater than 120 mg/m³×year and among smokers, those with the GA genotype of Ex2+37G>A in caspase-1 had a higher risk of silicosis than those with other genotypes (adjusted ORs[95%CIs] = 26.37[3.35–207.39] and 3.47[1.40–8.64], respectively).

Conclusions

Genetic polymorphisms in Nalp3 and caspase-1 may be associated with individual susceptibility to silicosis, especially when the polymorphisms interact with age, CDE, or smoking status.     

发根农杆菌Ri质粒及其在植物科学中的应用

阐述了发根农杆菌的性质及Ri质粒的结构和功能,介绍了毛状根的诱导及其鉴定方法,并对Ri质粒在植物基因工程、植物次生代谢产物生产、植物品种改良和植物栽培等方面的应用进行了综述。