HIV-mediated phosphatidylinositol 3-kinase/serine-threonine kinase activation in APCs leads to programmed death-1 ligand upregulation and suppression of HIV-specific CD8 T cells

Recent evidence demonstrates that HIV-1 infection leads to the attenuation of cellular immune responses, which has been correlated with the increased expression of programmed death (PD)-1 on virus-specific CD8(+) T cells. PD-1 is induced upon T cell activation, and its prolonged expression facilitates CD8(+) T cell inhibitory signals when bound to its B7 family ligands, PD-ligand (L)1/2, which are expressed on APCs. Importantly, early reports demonstrated that blockade of the PD-1/PD-L interaction by Abs may help to counter the development of immune exhaustion driven by HIV viral persistence. To better understand the regulation of the PD-1 pathway during HIV infection, we examined the ability of the virus to induce PD-L expression on macrophages and dendritic cells. We found a direct relationship between the infection of APCs and the expression of PD-L1 in which virus-mediated upregulation induced a state of nonresponsiveness in uninfected HIV-specific T cells. Furthermore, this exhaustion phenotype was revitalized by the blockade of PD-L1, after which T cells regained their capacity for proliferation and the secretion of proinflammatory cytokines IFN-γ, IL-2, and IL-12 upon restimulation. In addition, we identify a critical role for the PI3K/serine-threonine kinase signaling pathway in PD-L1 upregulation of APCs by HIV, because inhibition of these intracellular signal transducer enzymes significantly reduced PD-L1 induction by infection. These data identify a novel mechanism by which HIV exploits the immunosuppressive PD-1 pathway and suggest a new role for virus-infected cells in the local corruption of immune responses required for viral suppression.     

Effects of domestic wastewater slow infiltration on the growth of poplar 'Zhonglin 2001' plantation

A slow infiltration experiment with different hydraulic loads (0, 3, 6, 9, 12, and 15 cm per week) of domestic wastewater was conducted in a 'Zhonglin 2001' poplar plantation to study the effects of the wastewater slow infiltration on the growth of the plantation. Comparing with the control (0 cm), the other five treatments increased the soil organic matter, total N, total P, total K, and Na+ contents in the plantation averagely by 1.940 g x kg(-1), 0.115 g x kg(-1), 0.029 g x kg(-1), 1.454 g x kg(-1) and 0.030 g x kg(-1), respectively. At lower hydraulic loads (3-12 cm per week), the poplar biomass growth and the N, P and Na+ contents in different poplar organs averagely increased by 17.583 t x hm(-2) x a(-1), 3.086 g x kg(-1), 0.645 g x kg(-1), and 0.121 g x kg(-1), with the maximum (36.252 t x hm(-2) x a(-1), 13.162 g x kg(-1), 5.137 g x kg(-1), and 0.361 g x kg(-1), respectively) at hydraulic loads 6-12 cm per week. The further increase of the hydraulic load decreased the poplar biomass growth and the N, P and Na+ contents in different poplar organs. The K content in different poplar organs decreased with increasing hydraulic load. Treating with domestic wastewater increased the leaf length, decreased the leaf asymmetry, and delayed leaf-falling. At high hydraulic load (15 cm per week), the higher soil Na+ and water contents would threat the poplar growth. The proper domestic wastewater hydraulic loads for the growth of poplar 'Zhonglin 2001' plantation would be 3-12 cm per week.     

Flower-specific expression of <Emphasis Type="Italic">Arabidopsis</Emphasis><Emphasis Type="Italic">PCS1</Emphasis> driven by <Emphasis Type="Italic">AGAMOUS</Emphasis> second intron in tobacco decreases the fertility of transgenic plants

The PROMOTION OF CELL SURVIVAL 1 (PCS1) gene, encoding an aspartic protease, has an important role in determining the fate of cells in embryonic development and reproduction processes in Arabidopsis. To explore the potential function of the PCS1 gene in generating reproductive sterility, we placed the PCS1 gene under the control of an 1,869-bp nucleotide sequence from the 3′ end of the second intron (AG-I) of Arabidopsis AGAMOUS and CaMV 35S (–60) minimal promoter [AG-I-35S (–60)::PCS1], and introduced it into tobacco. RT–PCR results demonstrated that the PCS1 gene driven by AG-I-35S (–60) chimeric promoter was expressed only in anthers and carpels in the reproductive tissues of transgenic tobacco. Compared to wild-type plants, all AG-I-35S (–60) and AG-I-35S (–60)::PCS1 transgenic lines showed a normal phenotype throughout the vegetative growth phase. However, during the reproductive stage, most AG-I-35S (–60)::PCS1 transgenic plant anthers displayed delayed dehiscence, failed dehiscence, petalody and hypoplasia, and the pollen grains had different shapes and sizes with a distorted, shrunken, or collapsed morphology. Moreover, three transgenic lines, PCS1-1, PCS1-3 and PCS1-4, showed higher sterility than wild-type and AG-I-35S (–60) transgenic plants, respectively. These results showed that the construct of AG-I-35S (–60)::PCS1 was partially effective at preventing seed set and provided a novel sterility strategy.     

(+)-Borneol suppresses conditioned fear recall and anxiety-like behaviors in mice

Fear- and anxiety-related psychiatric disorders have been one of the major chronic diseases afflicting patients for decades, and new compounds for treating such disorders remain to be developed. (+)-Borneol, a bicyclic monoterpene found in several species of Artemisia and Dipterocarpaceae, is widely used for anxiety, pain and anesthesia in Chinese medicine. Meanwhile, it can potentiate GABA (γ-aminobutyric acid) activity directly in recombinant GABAA receptors. The present study was to investigate the effects of (+)-Borneol on both contextual and cued fear recall. Interestingly, microinjection of (+)-Borneol into the dorsal hippocampus inhibited 24 h and 7 d contextual fear, whereas its infusion into ventral hippocampus only reduced 24 h cued fear responses. Moreover, microinjection of (+)-Borneol into dorsal but not ventral hippocampus suppressed anxiety-like behaviors in the open field test, light/dark exploration and the elevated plus maze test. As selective GABA_A receptor antagonist bicuculline reversed the effect of (+)-Borneol on contextual fear paradigm and the drug potentiated GABA-evoked currents in acute hippocampus slices, modulation of the GABAergic neurotransmission may explain the effects of (+)-Borneol. Our findings suggest that (+)-Borneol can serve as a new therapeutic in fear- and anxiety-related disorders.     

Complete mitochondrial genome of Odontobutis haifengensis (Perciformes,Odontobutiae): A unique rearrangement of tRNAs and additional non-coding regions identified in the genus Odontobutis

Herein, the complete mitochondrial genome of Odontobutis haifengensis was sequenced for the first time. The O. haifengensis mitogenome was 17,016 bp in length and included 13 protein-coding genes, 22 transfer RNAs (tRNAs), 2 ribosomal RNAs (rRNAs), and a control region (CR). The genome organization, base composition, codon usage, and gene rearrangement was similar to other Odontobutis species. Furthermore, a tRNA gene rearrangement within the SLH cluster was found to be identical to other Odontobutis species. Moreover, the gene order and the positions of additional intergenic non-coding regions suggests that the observed unique gene rearrangement resulted from a tandem duplication and random loss of large-scale gene regions. Additionally, phylogenetic analysis showed that Odontobutis species form a monophyletic clade due to the conserved mitochondrial gene rearrangement. This study provides useful information that aids in a better understanding of mitogenomic diversity and evolutionary patterns of Odontobutidae species.     

药物注射联合针刀治疗肩周炎临床疗效及安全性分析

为探讨针刀联合曲安奈德、正清风痛宁、利多卡因治疗肩周炎的临床疗效及安全性分析,本研究选取2016年1月至2017年12月来东南大学附属中大医院疼痛科就诊肩周炎患者120例,随机数字表法分为药物治疗组40例(曲安奈德+正清风痛宁+利多卡因+臭氧治疗),针刀治疗组40例,综合治疗组40例(曲安奈德+正清风痛宁+利多卡因+臭氧+针刀治疗),对比分析各组治疗前后肩关节功能评分、视觉模拟评分法(visual analogue score, VAS)评分、不良反应发生率。结果显示,组内比较,3组治疗后VAS和肩关节功能评分与治疗前比较,差异具有统计学意义(p<0.001)。组间比较,治疗前3组VAS和肩关节功能评分比较,差异不具有统计学意义;综合治疗组各时间点VAS评分均低于药物及针刀治疗组,综合治疗组肩关节功能评分在治疗后1个月和2个月高于药物及针刀治疗组,差异具有统计学意义(p<0.001)。3组的不良反应发生率,差异不具有统计学意义(p>0.05)。综上所述,针刀治疗联合曲安奈德、正清风痛宁、利多卡因及臭氧在关节腔及关节周围注射治疗肩周炎安全有效,值得在临床中推广应用。     

cxcr2基因修饰小鼠骨髓间充质干细胞的构建与鉴定

目的构建小鼠CXC型趋化因子受体2(CXCR2)基因cxcr2过表达的骨髓间充质干细胞(Bone marrow mes-enchymal stem cell,BMSC)并进行鉴定。方法全骨髓贴壁法分离培养小鼠BMSC,采用流式细胞术检测干细胞抗原1(stem cell antigen-1,SCA-1)、CD44、CD43、CD45、IA/IE表达率,并诱导成骨分化。以含有小鼠cxcr2的质粒为模版进行PCR扩增,将获得的cxcr2克隆到慢病毒载体,命名为p Lenti-cxcr2-GZ;将其与慢病毒包装质粒共转染HEK-293T细胞,收获慢病毒后,通过离心法感染BMSC,经过1μg/mL zeocin压力选择建立了稳定表达CXCR2的小鼠BMSC(CXCR2-BMSC)。采用流式细胞术和RT-PCR分别检测其CXCR2蛋白和m RNA表达水平,Transwell趋化实验检测其迁移能力。结果 90%以上的第3代BMSC表达CD44、SCA-1,几乎不表达IA/IE、CD34、CD45,且成功诱导成骨分化。菌液PCR、质粒双酶切后,琼脂糖凝胶电泳鉴定结果得到特异、大小正确的条带及测序鉴定正确,表明成功构建了p Lenti-cxcr2-GZ表达质粒。流式细胞术和RT-PCR结果显示,CXCR2-BMSC的CXCR2蛋白和m RNA表达水平均明显高于对照组BMSC,差异有统计学意义(P<0.001)。Transwell结果显示,CXCR2-BMSC迁移能力高于对照组BMSC,差异有统计学意义(P<0.01)。结论利用慢病毒系统成功构建了稳定表达CXCR2的BM-SC,cxcr2基因修饰BMSC后可明显增加BMSC的迁移能力。     

Association between METTL3 gene polymorphisms and neuroblastoma susceptibility: A nine‐centre case‐control study

Neuroblastoma ranks as the most commonly seen and deadly solid tumour in infancy. The aberrant activity of m⁶A‐RNA methyltransferase METTL3 is involved in human cancers. Therefore, functional genetic variants in the METTL3 gene may contribute to neuroblastoma risk. In the current nine‐centre case‐control study, we aimed to analyse the association between the METTL3 gene single nucleotide polymorphisms (SNPs) and neuroblastoma susceptibility. We genotyped four METTL3 gene SNPs (rs1061026 T>G, rs1061027 C>A, rs1139130 A>G, and rs1263801 G>C) in 968 neuroblastoma patients and 1814 controls in China. We found significant associations between these SNPs and neuroblastoma risk in neither single‐locus nor combined analyses. Interestingly, in the stratified analysis, we observed a significant risk association with rs1061027 AA in subgroups of children ≤ 18 months of age (adjusted OR = 1.87, 95% CI = 1.03‐3.41, P = .040) and females (adjusted OR = 1.86, 95% CI = 1.07‐3.24, P = .028). Overall, we identified a significant association between METTL3 gene rs1061027 C>A polymorphism and neuroblastoma risk in children ≤18 months of age and females. Our findings provide novel insights into the genetic determinants of neuroblastoma.     

Effect of pinealectomy on the circadian clock of the chick retina under different monochromatic lights

The avian circadian rhythm pacemaker is composed of the retina, pineal gland and suprachiasmatic nucleus. As an intact input-pacemaker-output system, each of these structures is linked within a neuroendocrine loop to influence downstream processes and peripheral oscillations. While our previous study found that monochromatic light affected the circadian rhythms of clock genes in the chick retina, the effect of the pineal gland on the response of the retinal circadian clock under monochromatic light still remains unclear. In this study, a total of 144 chicks, including sham-operated and pinealectomized groups, were exposed to white, red, green or blue light. After 2 weeks of light illumination, the circadian expression of six core clock genes (cClock, cBmal1, cCry1, cCry2, cPer2 and cPer3), melanopsin (cOpn4-1, cOpn4-2), Arylalkylamine N-acetyltransferase (cAanat) and melatonin was examined in the retina. The cBmal1, cCry1, cPer2, cPer3, cOpn4-1, cOpn4-2 and cAanat genes as well as melatonin had circadian rhythmic expression in both the sham-operated and pinealectomized groups under different monochromatic lights, while cClock and cCry2 had arrhythmic 24 h profiles in all of the light-treated groups. After pinealectomy, the rhythmicity of the clock genes, melanopsins, cAanat and melatonin in the chick retina did not change, especially the mesors, amplitudes and phases of cBmal1, cOpn4-1, cOpn4-2, cAanat and melatonin. Compared to the white light group, however, green light increased the mRNA expression of the positive-regulating clock genes cBmal1, cAanat, cOpn4-1 and cOpn4-2 as well as the melatonin content in pinealectomized chicks, whereas red light decreased their expression. These results suggest that the chick retina is a relatively independent circadian oscillator from the pineal gland, whose circadian rhythmicity (including photoreception, molecular clock and melatonin output) is not altered after pinealectomization. Moreover, green light increases ocular cAanat expression and melatonin synthesis by accelerating the expression of melanopsin and positive-regulating clock genes cBmal1 and cClock.     

全球陆地保护地与城市距离变化分析

在城市用地和保护地都快速扩张的背景下, 保护地与城市之间的距离在急剧缩小, 然而这并未引起人们的足够关注。城市对保护地的负面影响具有尺度效应, 且随着距离的接近, 负面影响也将加剧, 因此保护地与城市距离的远近可成为衡量负面影响大小的重要依据。本文基于全球保护地和大城市及城市用地分布数据, 对全球、洲际、地区和国家尺度1950-2010年城市与保护地距离的变化进行分析。结果表明: (1)在4个尺度上, 保护地与城市的距离都在不断缩小。欧洲和西欧是保护地与城市距离最近的洲和地区, 而大洋洲和澳大利亚及新西兰则是距离最远的洲和地区。在面积排名前20的保护地大国中, 中国是保护地与城市平均最近距离最小的国家, 其与50万以上人口城市的平均最近距离在2010年仅为143.5 km。(2)根据城市与保护地距离的现状及其变化, 可将保护地排名前60的国家分成5类: (a)距离很近, 靠近速度慢, 如西欧国家; (b)距离近, 靠近速度适中, 如中国、美国; (c)距离较近, 靠近速度快, 如沙特阿拉伯、厄瓜多尔; (d)距离较远, 靠近速度较慢, 如巴西、加拿大、俄罗斯联邦; (e)距离远, 靠近速度较快, 如澳大利亚、非洲大多数国家。(3)全球范围内, 越来越多生物多样性较高的保护地将面临被城市影响的境地。该结果以期引起大家对全球保护地与城市距离急剧缩短现象的关注和警惕。