SEQUENCES OF LLANDOVERIAN CHITINOZOANS IN YANGZl REGION

This paper is dedicated as a token of homage and gratitude to Prof. Mu. En-zhi, the nestor in the field of graptolite studies, who introduced us chitinozoan studies with constant supports in many ways, and who died on 8th April, 1987. The Palaeontological Society of China has decided to publish a specieal volume in memory of this outstanding scientist.     

Glucose and fatty acids synergize to promote B-cell apoptosis through activation of glycogen synthase kinase 3β independent of JNK activation

Background

The combination of elevated glucose and free-fatty acids (FFA), prevalent in diabetes, has been suggested to be a major contributor to pancreatic β-cell death. This study examines the synergistic effects of glucose and FFA on β-cell apoptosis and the molecular mechanisms involved. Mouse insulinoma cells and primary islets were treated with palmitate at increasing glucose and effects on apoptosis, endoplasmic reticulum (ER) stress and insulin receptor substrate (IRS) signaling were examined.

Principal Findings

Increasing glucose (5–25 mM) with palmitate (400 µM) had synergistic effects on apoptosis. Jun NH2-terminal kinase (JNK) activation peaked at the lowest glucose concentration, in contrast to a progressive reduction in IRS2 protein and impairment of insulin receptor substrate signaling. A synergistic effect was observed on activation of ER stress markers, along with recruitment of SREBP1 to the nucleus. These findings were confirmed in primary islets. The above effects associated with an increase in glycogen synthase kinase 3β (Gsk3β) activity and were reversed along with apoptosis by an adenovirus expressing a kinase dead Gsk3β.

Conclusions/Significance

Glucose in the presence of FFA results in synergistic effects on ER stress, impaired insulin receptor substrate signaling and Gsk3β activation. The data support the importance of controlling both hyperglycemia and hyperlipidemia in the management of Type 2 diabetes, and identify pancreatic islet β-cell Gsk3β as a potential therapeutic target.     

Combined DNA vaccines formulated in DDA enhance protective immunity against tuberculosis

This study evaluated the adjuvant Dimethyldioctyldecyl Ammonium Bromide (DDA) effect on the protective immunity induced by a combination of plasmids containing genes encoding antigens Ag85B, MPT-83, and ESAT-6 from Mycobacterium tuberculosis. The combined DNA vaccines in DDA resulted in significant increases in both specific IgG and splenic T-cell-derived Th1-type cytokine gamma interferon (IFN-gamma) production in response to the three purified antigens when compared to that of combined DNA vaccines in saline. Vaccines in DDA increased the protective efficacy of mice challenged with M. tuberculosis H37Rv as measured by reduced relative CFU counts in their lungs. Mice immunized with the combined DNA vaccines were shown to limit the growth of tubercle bacilli both in lungs and in spleens. Histopathological analyses showed that vaccinated mice had substantially improved postinfection lung pathology relative to the controls. We suggest that our combination of antigens together with DDA formulation may provide a new insight into tuberculosis prevention.     

BMP9经Smad信号通路调控iSCAP成骨/成牙本质分化

目的：研究BMP9是否能够激活 iSCAP细胞中的Smad信号通路,以及Smad信号通路在BMP9诱导iSCAP细胞成骨/成牙本质向分化过程中的作用。方法：首先,采用Western印迹实验检测Ad-BMP9转染iSCAP后Smad1/5/8蛋白的磷酸化水平。随后,利用dnALK1重组腺病毒和BMP9条件培养基作用于iSCAP,Western印迹实验检测Smad1/5/8蛋白磷酸化水平;采用碱性磷酸酶（ALP）活性检测和染色方法分析早期成骨/成牙本质指标变化,茜素红染色法检测钙盐沉积程度;RT-PCR成骨/成牙本质相关基因Runx2、OCN、OPN和DMP1表达的影响。结果：BMP9可上调iSCAP中Smad1/5/8的磷酸化水平;dnALK1抑制BMP9条件培养基作用后,可抑制Smad1/5/8的磷酸化,iSCAP细胞中早期成骨/成牙本质标志物ALP活性和晚期成骨/成牙本质标志钙盐结节减少,重要成骨转录因子Runx2基因表达减少,成骨/成牙本质相关基因OCN、OPN、DMP1的表达也受到了抑制。结论：Smad信号通路在BMP9诱导iSCAP成骨/成牙本质过程中存在并起着重要作用。     

Hypoxic Preconditioning Augments the Therapeutic Efficacy of Bone Marrow Stromal Cells in a Rat Ischemic Stroke Model

Transplantation of bone marrow stromal cells (BMSCs) is a promising therapy for ischemic stroke, but the poor oxygen environment in brain lesions limits the efficacy of cell-based therapies. Here, we tested whether hypoxic preconditioning (HP) could augment the efficacy of BMSC transplantation in a rat ischemic stroke model and investigated the underlying mechanism of the effect of HP. In vitro, BMSCs were divided into five passage (P0, P1, P2, P3, and P4) groups, and HP was applied to the groups by incubating the cells with 1% oxygen for 0, 4, 8, 12, and 24 h, respectively. We demonstrated that the expression of hypoxia-inducible factor-1α (HIF-1α) was increased in the HP-treated BMSCs, while their viability was unchanged. We also found that HP decreased the apoptosis of BMSCs during subsequent simulated ischemia–reperfusion (I/R) injury, especially in the 8-h HP group. In vivo, a rat transient focal cerebral ischemia model was established. These rats were administered normal cultured BMSCs (N-BMSCs), HP-treated BMSCs (H-BMSCs), or DMEM cell culture medium (control) at 24 h after the ischemic insult. Compared with the DMEM control group, the two BMSC-transplanted groups exhibited significantly improved functional recovery and reduced infarct volume, especially the H-BMSC group. Moreover, HP decreased neuronal apoptosis and enhanced the expression of BDNF and VEGF in the ischemic brain. Survival and differentiation of transplanted BMSCs were also increased by HP, and the quantity of engrafted BMSCs was significantly correlated with neurological function improvement. These results suggest that HP may enhance the therapeutic efficacy of BMSCs in an ischemic stroke model. The underlying mechanism likely involves the inhibition of caspase-3 activation and an increasing expression of HIF-1α, which promotes angiogenesis and neurogenesis and thereby reduces neuronal death and improves neurological function.     

氟西汀联合同步放化疗治疗局部晚期非小细胞肺癌的临床观察

目的：观察氟西汀联合同步放化疗治疗局部晚期非小细胞肺癌（none small cells lung carcinoma,NSCLC）的临床疗效及其安全性。方法：选择2010年10月～2011年4月我院收治的III期不能手术的NSCLC患者47例,根据患者的入院顺序,随机分为两组,同步放化疗组（对照组）22例,接受三维适形或调强放疗：肿瘤处方剂量60~66Gy,常规分割：1．8～2．0Gy／次;放疗期间同步两周期“紫杉醇＋顺铂”方案化疗,放疗后再原方案巩固化疗2--3个周期;氟西汀联合治疗组（实验组）25例,从同步放化疗开始起同时服用氟西汀（20-40mg／day）,持续服药半年。随访至1年,观察和评价两组的疗效以及不良反应的发生情况。结果：对照组与实验组的客观有效率分别为77-3％（17／22）和80％（20／25）（P〉0．05）;1年生存率分别为68．2％（15／22）和80％（20／25）（P〉0．05）;1年局控率分别为45．5％（10／22）和76％（19／25）,差异有统计学意义（P〈0．05）。治疗后,实验组患者CD＋／CD8＋比率由1．34±0．23升至1．58±0．22（P〈0．05）,而汉密尔顿抑郁量表（HAMD）总分由13．4±4．8降至9．6±3（P〈0．05）;全组患者主要不良反应为骨髓抑制、消化道反应、放射性食管炎和放射性肺炎,来发生4级不良反应,两组3级不良反应发生率无明显差异（P〉0．05）。结论：对于不能手术的局部晚期NSCLC患者,在同步放化疗的基础上联合氟西汀治疗可以提高肿瘤的1年局控率,促进抗肿瘤免疫,并缓解患者的抑郁情绪,且不加重不良反应。     

Genome-wide association study dissects the genetic control of plant height and branch number in response to low-phosphorus stress in Brassica napus

Background and AimsOilseed rape (Brassica napus) is one of the most important oil crops worldwide. Phosphorus (P) deficiency severely decreases the plant height and branch number of B. napus. However, the genetic bases controlling plant height and branch number in B. napus under P deficiency remain largely unknown. This study aims to mine candidate genes for plant height and branch number by genome-wide association study (GWAS) and determine low-P-tolerance haplotypes.MethodsAn association panel of B. napus was grown in the field with a low P supply (P, 0 kg ha⁻¹) and a sufficient P supply (P, 40 kg ha⁻¹) across 2 years and plant height and branch number were investigated. More than five million single-nucleotide polymorphisms (SNPs) were used to conduct GWAS of plant height and branch number at two contrasting P supplies.Key ResultsA total of 2127 SNPs were strongly associated (P < 6·25 × 10⁻⁰⁷) with plant height and branch number at two P supplies. There was significant correlation between phenotypic variation and the number of favourable alleles of associated loci on chromosomes A10 (chrA10_821671) and C08 (chrC08_27999846), which will contribute to breeding improvement by aggregating these SNPs. BnaA10g09290D and BnaC08g26640D were identified to be associated with chrA10_821671 and chrC08_27999846, respectively. Candidate gene association analysis and haplotype analysis showed that the inbred lines carrying ATT at BnaA10g09290Hap1 and AAT at BnaC08g26640Hap1 had greater plant height than lines carrying other haplotype alleles at low P supply.ConclusionOur results demonstrate the power of GWAS in identifying genes of interest in B. napus and provided insights into the genetic basis of plant height and branch number at low P supply in B. napus. Candidate genes and favourable haplotypes may facilitate marker-based breeding efforts aimed at improving P use efficiency in B. napus.     

中国两栖动物受威胁现状评估

为了了解我国两栖动物受威胁现状和致危因素, 进而制定相关的保护措施和开展国际合作, 本文依据中国两栖动物野生种群与生境现状, 利用《IUCN物种红色名录濒危等级和标准》(3.1版)和《IUCN物种红色名录标准在国家或地区的应用指南》(4.0版), 对中国已知的408种两栖动物的濒危状况进行了评估, 并编制了《中国两栖动物红色名录》。评估结果表明: 中国两栖动物有1种灭绝, 1种区域灭绝, 受威胁的两栖动物共计176种, 占评估物种总数的43.1%, 明显高于《IUCN濒危物种红色名录》(2015)的物种受威胁率(30.8%)。中国两栖动物特有种272种, 其中48.9%属于受威胁物种。中国两栖动物受威胁比例最高的目是有尾目(63.4%), 明显高于无尾目(39.0%); 受威胁比例最高的科是隐鳃鲵科(Cryptobranchidae) (仅有1种, 100%受威胁), 小鲵科(Hynobiidae) (86.7%)和叉舌蛙科(Dicroglossidae) (78.1%)。有11个省区的受威胁物种数占本省区两栖动物物种总数的30%及以上, 前3位分别是四川(40.8%)、广西(39.2%)和云南(37%)。中国大多数两栖动物物种分布在西南山地和华南地区, 以海拔2,000 m以下区域为主。栖息地退化或丧失、捕捉、环境污染列受威胁两栖动物致危因子的前3位。鉴于中国两栖动物区系的复杂性和独特性, 进一步加强两栖动物资源调查、种群和生境监测及相关科学研究, 仍是今后一段时期开展两栖动物多样性保护和濒危物种拯救行动的关键性基础工作。     

Efficient production of l-lactic acid from hydrolysate of Jerusalem artichoke with immobilized cells of Lactococcus lactis in fibrous bed bioreactors

Hydrolysate of Jerusalem artichoke was applied for the production of l-lactic acid by immobilized Lactococcus lactis cells in a fibrous bed bioreactor system. Preliminary experiments had indicated that the high quality hydrolysate, which was derived from the 40min acid treatment at 95°C and pH 1.8, was sufficient to support the cell growth and synthesis of l-lactic acid. With the addition of 5g/l yeast extract, the fermentative performance of free cell system was evidently improved. After the basal settlement of hydrolysate based fermentation, the batch mode and the fed-batch mode fermentation were carried out in the free cell system and the fibrous bed bioreactor system, respectively. In all cases the immobilized cells presented the superior ability to produce l-lactic acid. The comparison of batch mode and fed-batch mode also indicated that the growth-limiting feeding strategy could reduce the lag phase of fermentation process and enhance the production of l-lactic acid. The achieved maximum concentration of l-lactic acid was 142g/l in the fed-batch mode. Subsequent repeated-batch fermentation of the fibrous bed bioreactor system had further exhibited the persistence and stability of this system for the high production of l-lactic acid in a long term. Our work suggested the great potential of the fibrous bed bioreactor system and hydrolysate of J. artichoke in the economical production of l-lactic acid at industrial scale.