Cancer-initiating cells derived from human rectal adenocarcinoma tissues carry mesenchymal phenotypes and resist drug therapies

Accumulating evidence indicates that cancer-initiating cells (CICs) are responsible for cancer initiation, relapse, and metastasis. Colorectal carcinoma (CRC) is typically classified into proximal colon, distal colon, and rectal cancer. The gradual changes in CRC molecular features within the bowel may have considerable implications in colon and rectal CICs. Unfortunately, limited information is available on CICs derived from rectal cancer, although colon CICs have been described. Here we identified rectal CICs (R-CICs) that possess differentiation potential in tumors derived from patients with rectal adenocarcinoma. The R-CICs carried both CD44 and CD54 surface markers, while R-CICs and their immediate progenies carried potential epithelial–mesenchymal transition characteristics. These R-CICs generated tumors similar to their tumor of origin when injected into immunodeficient mice, differentiated into rectal epithelial cells in vitro, and were capable of self-renewal both in vitro and in vivo. More importantly, subpopulations of R-CICs resisted both 5-fluorouracil/calcium folinate/oxaliplatin (FolFox) and cetuximab treatment, which are the most common therapeutic regimens used for patients with advanced or metastatic rectal cancer. Thus, the identification, expansion, and properties of R-CICs provide an ideal cellular model to further investigate tumor progression and determine therapeutic resistance in these patients.     

雷公藤悬浮细胞原生质体的制备及瞬时转化体系的建立

为探索药用植物雷公藤(Tripterygium wilfordii)悬浮细胞原生质体提取的最优条件,并建立雷公藤原生质体瞬时转化体系,以雷公藤悬浮细胞为材料,对酶解液配比、酶解时间、甘露醇浓度及处理转速进行考察。用PEG介导的瞬时转化法将外源基因转化到雷公藤原生质体中。结果表明,以雷公藤悬浮细胞为材料提取原生质体的最佳条件是酶液配比为2.0%纤维素酶+0.5%果胶酶+0.5%离析酶,甘露醇浓度为0.6 mol·L–1,酶解10小时,处理转速为67×g;用PEG介导法将含有编码GFP的植物表达载体转化雷公藤悬浮细胞原生质体,激光共聚焦扫描显微镜下细胞显示绿色荧光。通过实验筛选得到雷公藤悬浮细胞原生质体的最佳提取条件,建立了雷公藤悬浮细胞原生质体的瞬时转化体系,为进一步开展雷公藤功能基因及合成生物学研究奠定了基础。     

A Computational Approach to Characterizing the Impact of Social Influence on Individuals’ Vaccination Decision Making

In modeling individuals vaccination decision making, existing studies have typically used the payoff-based (e.g., game-theoretical) approaches that evaluate the risks and benefits of vaccination. In reality, whether an individual takes vaccine or not is also influenced by the decisions of others, i.e., due to the impact of social influence. In this regard, we present a dual-perspective view on individuals decision making that incorporates both the cost analysis of vaccination and the impact of social influence. In doing so, we consider a group of individuals making their vaccination decisions by both minimizing the associated costs and evaluating the decisions of others. We apply social impact theory (SIT) to characterize the impact of social influence with respect to individuals interaction relationships. By doing so, we propose a novel modeling framework that integrates an extended SIT-based characterization of social influence with a game-theoretical analysis of cost minimization. We consider the scenario of voluntary vaccination against an influenza-like disease through a series of simulations. We investigate the steady state of individuals’ decision making, and thus, assess the impact of social influence by evaluating the coverage of vaccination for infectious diseases control. Our simulation results suggest that individuals high conformity to social influence will increase the vaccination coverage if the cost of vaccination is low, and conversely, will decrease it if the cost is high. Interestingly, if individuals are social followers, the resulting vaccination coverage would converge to a certain level, depending on individuals’ initial level of vaccination willingness rather than the associated costs. We conclude that social influence will have an impact on the control of an infectious disease as they can affect the vaccination coverage. In this respect, our work can provide a means for modeling the impact of social influence as well as for estimating the effectiveness of a voluntary vaccination program.     

Cellular and gene expression responses involved in the rapid growth inhibition of human cancer cells by RNA interference-mediated depletion of telomerase RNA

Inhibition of the up-regulated telomerase activity in cancer cells has previously been shown to slow cell growth but only after prior telomere shortening. Previously, we have reported that, unexpectedly, a hairpin short interfering RNA specifically targeting human telomerase RNA rapidly inhibits the growth of human cancer cells independently of p53 or telomere length and without bulk telomere shortening (Li, S., Rosenberg, J. E., Donjacour, A. A., Botchkina, I. L., Hom, Y. K., Cunha, G. R., and Blackburn, E. H. (2004) Cancer Res. 64, 4833-4840). Here we have demonstrated that such telomerase RNA knockdown in cancer cells does not cause telomere uncapping but rather induces changes in the global gene expression profile indicative of a novel response pathway, which includes suppression of specific genes implicated in angiogenesis and metastasis, and is distinct from the expression profile changes induced by telomere-uncapping mutant template telomerase RNAs. These cellular responses to depleting telomerase in human cancer cells together suggest that cancer cells are "telomerase-addicted" and uncover functions of telomerase in tumor growth and progression in addition to telomere maintenance.     

渭北旱塬保护性耕作对冬小麦-春玉米轮作田蓄水保墒效果和产量的影响

通过2007—2010年田间定位试验,研究了平衡施肥、常规施肥和无肥(或低肥)条件下,免耕、深松和翻耕处理对渭北旱塬冬小麦-春玉米轮作田土壤贮水量、作物产量、水分利用效率(WUE)和纯收益的影响.结果表明:休闲期免耕处理蓄水保墒效果最好,深松次之,翻耕最差;轮作田生育期内免耕和深松处理0~200 cm平均土壤贮水量分别较翻耕提高6.7%和1.9%;各施肥条件下作物产量、WUE和纯收益均以深松处理最高,且以平衡施肥深松处理表现最好,2007—2008年冬小麦、2009年春玉米、2009—2010年冬小麦产量分别为6909、9689、5589 kg.hm-2,WUE分别为18.5、25.2、23.0 kg.hm-2.mm-1,纯收益分别为5034、5045、7098元.hm-2.因此,平衡施肥与深松组合处理的蓄水保墒和增产增收效果最好,是渭北旱塬冬小麦-春玉米轮作田较适合的施肥耕作模式.     

PGE2抑制肿瘤坏死因子诱导的成骨细胞凋亡

前列腺素E2(PGE2)通过自分泌或旁分泌方式调节成骨细胞的增殖和分化。本文以小鼠原代成骨细胞和成骨样细胞MC3T3-E1为实验材料,研究了PGE2对肿瘤坏死因子α(TNF-α)诱导的成骨细胞凋亡的调节作用。检测发现,振荡型流体剪切力(OFSS)刺激可诱导成骨细胞内环氧合酶2(COX-2)表达升高,进而促进PGE2合成,并抑制TNF-α诱导的成骨细胞凋亡。COX-2选择性活性抑制剂NS-398显著促进TNF-α诱导的成骨细胞内半胱天冬酶3(caspase-3)的激活,且呈时间依赖性。Hoechst 33258/PI染色检测发现,NS-398促使TNF-α诱导的成骨细胞膜通透性进一步增强,核染色质浓缩加剧,而PGE2可显著抑制这一效应。Caspase-3活性检测证实,NS-398显著促进TNF-α诱导的成骨细胞内caspase-3活性增强,外源性PGE2可有效对抗该效应。这些结果表明,内源性和外源性PGE2可抑制TNF-α诱导的成骨细胞凋亡发生。     

三倍体品种的选育和利用

概述了三倍体生物的两大基本特征(细胞巨大性和不育性)及其产生原因,对有很好经济和社会效益的三倍体杨树、甜菜、无籽西瓜和某些海洋生物选育利用作了简要介绍、展示了三倍体品种选育利用的美好前景。     

One-step "green" preparation of graphene nanosheets and carbon nanospheres mixture by electrolyzing graphite rob and its application for glucose biosensing

The graphene nanosheets and carbon nanospheres mixture (GNS–CNS) was prepared by electrolyzing graphite rob in KNO₃ solution under constant current, which was characterized by TEM, AFM, SEM, FT-IR, XRD, XPS, TGA and UV–vis. The nano-mixture can keep stable in water for more than one month. Based on this kind of mixture material, a novel electrochemical biosensing platform for glucose determination was developed. Cyclic voltammetry of glucose oxidase (GOD) immobilized on GNS–CNS/GCE exhibited a pair of well-defined quasi-reversible redox peaks at −0.488 V (E_pa) and −0.509 V (E_pc) by direct electron transfer between the protein and the electrode. The charge-transfer coefficient (α) was 0.51, the electron transfer rate constant was 2.64 s⁻¹ and the surface coverage of HRP was 3.18 × 10⁻¹⁰ mol cm⁻². The immobilized GOD could retain its bioactivity and catalyze the reduction of dissolved oxygen. The glucose biosensor has a linear range from 0.4 to 20 mM with detection limit of 0.1 mM. Moreover, the biosensor exhibits acceptable reproducibility and storage stability. The fabricated biosensor was further used to determine glucose in human plasma sample with the recoveries from 96.83% to 105.52%. Therefore, GOD/GNS–CNS/GCE could be promisingly applied to determine blood sugar concentration in the practical clinical analysis.     

人参皂甙Rg1对体外人胃癌细胞增殖的抑制作用及机制

本研究用不同浓度人参皂甙Rg1作用人胃癌BGC-823细胞24 h、48 h和72 h,采用MTT法、流式细胞术及半定量RT-PCR检测GS-Rg1对胃癌细胞的增殖抑制作用、细胞周期分布时相和p16~(INK4a)、p21~(WAF1)表达水平的影响,以探讨人参皂甙Rg1对人胃癌BGC-823细胞增殖的抑制作用及机制。结果表明,随着作用时间和浓度的增加,人参皂甙Rg1对胃癌细胞增殖抑制作用逐渐增强(P<0.05),G_0/G_1期细胞比例增加,G_2/S期细胞比例下降,p16~(INK4a)、p21~(WAF1)基因水平上调。上述结果提示人参皂甙Rg1能抑制体外培养的胃癌BGC-823细胞增殖,其机制可能与上调肿瘤细胞内细胞周期蛋白依赖激酶抑制因子p16~(INK4a)及p21~(WAF1)mRNA的表达有关。