The combination therapy of oncolytic HSV-1 armed with anti-PD-1 antibody and IL-12 enhances anti-tumor efficacy

Cancer immunotherapy is a new therapeutic strategy for cancer treatment that targets tumors by improving or restoring immune system function. Therapies targeting immune checkpoint molecules have exerted potent anti-tumor effects and prolonged the overall survival rate of patients. However, only a small number of patients benefit from the treatment. Oncolytic viruses exert anti-tumor effects by regulating the tumor microenvironment and affecting multiple steps of tumor immune circulation. In this study, we engineered two oncolytic viruses that express mouse anti-PD-1 antibody (VT1093M) or mouse IL-12 (VT1092M). We found that both oncolytic viruses showed significant anti-tumor effects in a murine CT26 colon adenocarcinoma model. Importantly, the intratumoral combined injection with VT1092M and VT1093M inhibited growth of the primary tumor, prevented growth of the contralateral untreated tumor, produced a vaccine-like response, activated antigen-specific T cell responses and prolonged the overall survival rate of mice. These results indicate that combination therapy with the engineered oncolytic virus may represent a potent immunotherapy strategy for cancer patients, especially those resistant to PD-1/PD-L1 blockade therapy.     

Driving reactive nitrogen emissions in China: Competition between scale and efficiency

Reactive nitrogen (Nr) emissions aggravate air and water pollution across the world. The factors influencing Nr emissions have not been clearly uncovered, especially for regions under rapid economic growth. Here we modeled total Nr emissions in mainland China and analyzed factors driving their growth during the decade (2000–2010) of fastest socioeconomic development. Results show that total Nr emissions increased from 24.9 terrogram (Tg) to 35.2 Tg, a 41.7% increase with an average annual growth rate of 3.5%. Agricultural activities, including crop planting and livestock and poultry breeding, together took a substantial but decreasing share, from 75.2% in 2000 to 61.4% in 2010. Industrial wastewater discharge, energy use, and crop production are the three largest sources contributing to the Nr emissions growth. Factors related to scale (e.g., the amount of industrial energy use) led to a growth in Nr emissions, and factors related to efficiency (e.g., industrial energy use per unit of economic output) contributed to reduction. The decreasing effect of efficiency gains, however, was still unable to overcome the increasing effect of the activity scale. More in-depth research studies on mitigation strategies are required, to inform the decoupling between socioeconomic development and Nr emissions.     

喀斯特常绿落叶阔叶林木本植物功能性状变异及其适应策略

叶片功能性状能反映植物对环境的高度适应能力和复杂生境下的自我调控能力,同时也能反映植物的基本特征和对资源的有效利用率。以木论国家级自然保护区喀斯特常绿落叶阔叶林144种优势木本植物为研究对象,测定其叶厚(LT)、叶面积(LA)、比叶面积(SLA)、叶长宽比(L/W)、叶组织密度(LTD)叶片形态性状和12种叶元素性状特征及变异程度,并探讨植物对喀斯特生境的适应策略。结果表明：17个性状变异程度不同,其中叶面积变异系数最大,达到133.31%,叶片碳变异系数最小,为7.73%,叶元素变异程度普遍高于叶形态性状变异程度。不同叶习性物种间叶厚、比叶面积、叶长宽比、叶氮含量性状差异达到显著水平。部分叶性状呈显著相关,得到一系列最佳功能性状组合,体现植物对喀斯特地区特殊生境的适应性。沿着性状贡献率较高的PC1轴,能够定义出叶经济谱,大部分常绿植物采取经济保守策略,而大部分落叶植物则聚集在资源获取的一侧。相较于邻近非喀斯特地区,喀斯特地区植物有较小的LA、SLA。这些结果体现了喀斯特地区植物叶片形成的不同叶性状特征,以及分布于经济谱两端的常绿和落叶植物的不同资源获取策略,揭示了植物对生境的适应策略...     

The circadian regulation of extracellular ATP

Extracellular ATP is a potent signaling molecule released from various cells throughout the body and is intimately involved in the pathophysiological functions of the nervous system and immune system by activating P2 purinergic receptors. Recent increasingly studies showed that extracellular ATP exhibits circadian oscillation with an approximately 24-h periodicity, which participates in regulatory pathways of central oscillator suprachiasmatic nucleus and peripheral oscillator bladder, respectively. Oscillators modulate the protein expression of ATP release channels and ectonucleotidase activity through clock genes; indeed, real-time alterations of ATP release and degradation determine outcomes of temporal character on extracellular ATP rhythm. The regulatory pathways on extracellular ATP rhythm are different in central and peripheral systems. In this review, we summarize the circadian rhythm of extracellular ATP and discuss several circadian regulatory pathways in different organs via ATP release and degradation, to provide a new understanding for purinergic signaling in the regulatory mechanism of circadian rhythm and a potential target to research the circadian regulation of extracellular ATP in other circadian oscillators.     

杨树胞外蛋白的提取分离及2-D电泳体系的建立

该研究以美洲黑杨杂种优良无性系NL895杨(Populus deltoides×Populus euramericana cv.)组培苗叶片和茎段为研究对象,对NL895杨叶片细胞壁蛋白(cell wall proteins,CWPs)和茎段质外体蛋白(apoplastic proteins,APPs)的提取、分离和双向电泳等技术进行了系统研究。结果表明:10g以上叶片、超声波破碎10min、CaCl2法提取的细胞壁蛋白效果较好,经G-6-PDH酶活性检测,提取的细胞壁蛋白胞质污染率较低;真空渗透法提取的茎段质外体蛋白胞质污染率较前者高,但在允许范围之内。TCA/丙酮沉淀法纯化提取的细胞壁蛋白、pH 4~7的24cm胶条、上样量为500μg的双向电泳体系,其蛋白电泳图谱中的斑点多而清晰,斑点数达550多个,是叶片细胞壁蛋白电泳分析较适合的体系;pH 3~10胶条对茎段质外体蛋白的电泳分离效果较好。该研究初步建立了杨树胞外蛋白的提取、分离及2-DE电泳体系,为木本植物胞外蛋白的研究奠定了基础。     

Cloning and Drought Resistance Analysis of Soybean <i>GmHsps_p23-like</i> Gene

Soybean (Glycine max (L.) Merr.) is an important cultivated crop, which requires much water during its growth, and drought seriously affects soybean yields. Studies have shown that the expression of small heat shock proteins can enhance drought resistance, cold resistance and salt resistance of plants. In this experiment, soybean GmHsps_p23-like gene was successfully cloned by RT-PCR, the protein encoded by the GmHsps_p23-like gene was subjected to bioinformatics analysis, and the pCAMBIA3301-GmHsps_p23-like overexpression vector and pCBSG015-GmHsps_p23-like gene editing vector were constructed. Agrobacterium-mediated method was used to transform soybeans to obtain positive plants. RT-PCR detection, rehydration experiment and drought resistance physiological and biochemical index detection were performed on the T₂ generation positive transgenic soybean plants identified by PCR and Southern hybridization. The results showed that the overexpression vector plant GmHsps_p23-like gene expression increased. After rehydration, the transgenic overexpression plants returned to normal growth, and the damage to the plants was low. After drought stress, the SOD and POD activities and the PRO content of the transgenic overexpression plants increased, while the MDA content decreased. The reverse was true for soybean plants with genetically modified editing vectors. The drought resistance of the overexpressed soybeans under drought stress was higher than that of the control group, and had a stronger drought resistance. It showed that the expression of soybean GmHsps_p23-like gene can improve the drought resistance of soybean. The cloning and functional verification of soybean GmHsps_p23-like gene had not been reported yet. This is the first time that PCR technology has been used to amplify the soybean GmHsps_p23-like gene and construct an expression vector for this gene. This research has laid the foundation for transgenic technology to improve plant drought resistance and cultivate new drought-resistant transgenic soybean varieties.     

Endophytic microbes <Emphasis Type="Italic">Bacillus</Emphasis> sp. LZR216-regulated root development is dependent on polar auxin transport in <Emphasis Type="Italic">Arabidopsis</Emphasis> seedlings

Key message

Endophytic microbes Bacillus sp. LZR216 isolated from Arabidopsis root promoted Arabidopsis seedlings growth. It may be achieved by promoting the lateral root growth and inhibiting the primary root elongation.

Abstract

Plant roots are colonized by an immense number of microbes, including epiphytic and endophytic microbes. It was found that they have the ability to promote plant growth and protect roots from biotic and abiotic stresses. But little is known about the mechanism of the endophytic microbes-regulated root development. We isolated and identified a Bacillus sp., named as LZR216, of endophytic bacteria from Arabidopsis root. By employing a sterile experimental system, we found that LZR216 promoted the Arabidopsis seedlings growth, which may be achieved by promoting the lateral root growth and inhibiting the primary root elongation. By testing the cell type-specific developmental markers, we demonstrated that Bacillus sp. LZR216 increases the DR5::GUS and DR5::GFP expression but decreases the CYCB1;1::GUS expression in Arabidopsis root tips. Further studies indicated that LZR216 is able to inhibit the meristematic length and decrease the cell division capability but has little effect on the quiescent center function of the root meristem. Subsequently, it was also shown that LZR216 has no significant effects on the primary root length of the pin2 and aux1-7 mutants. Furthermore, LZR216 down-regulates the levels of PIN1-GFP, PIN2-GFP, PIN3-GFP, and AUX1-YFP. In addition, the wild-type Arabidopsis seedlings in the present of 1 or 5 µM NPA (an auxin transport inhibitor) were insensitive to LZR216-inhibited primary root elongation. Collectively, LZR216 regulates the development of root system architecture depending on polar auxin transport. This study shows a new insight on the ability of beneficial endophytic bacteria in regulating postembryonic root development.

     

喀斯特峰丛洼地不同类型森林养分循环特征

以中国西南喀斯特峰丛洼地为研究区域用标准木法和收获法对人工林、次生林、原生林3个不同类型森林的6个代表性群落的生物量、营养元素生物循环量及循环特征进行了研究。结果表明:(1)不同类型森林群落乔木各器官的养分含量大小顺序为:叶枝根干,林下植被层和凋落物层的养分含量比较高,其含量普遍高于乔木层各组分,仅次于乔木叶片;各组分中营养元素以K、Ca最高,P、Mg最低;(2)3种类型森林间乔木层的养分积累量总规律表现为原生林(4540.30 kg/hm~2)次生林(2107.09 kg/hm~2)人工林(719.51 kg/hm~2),分别占林分养分积累量的88.30%、79.57%和62.60%;(3)3种类型森林生态系统养分总贮量相差不大,均主要集中在土壤层在各层分配格局有所差异;营养元素的年吸收量和年归还量均为次生林原生林人工林,年吸收量分别为:418.80、271.17和148.79 kg hm~(-2)a~(-1);年归还量分别为:182.98、111.43和43.37 kg hm_(-2)a~(-1);(4)不同类型森林养分利用系数总规律为人工林(0.35)次生林(0.20)原生林(0.10);循环系数则相反,为原生林(0.48)次生林(0.46)人工林(0.30);而周转时间为原生林(37.32)人工林(18.63)次生林(13.93)。喀斯特峰丛洼地土层薄,养分贮存能力差,森林养分循环能力相对较弱,沿着强、中、弱干扰递减梯度,3种类型森林养分利用效率和循环能力呈增长趋势。     

Comparative Genomic Analysis of 45 Type Strains of the Genus Bifidobacterium: A Snapshot of Its Genetic Diversity and Evolution

Bifidobacteria are well known for their human health-promoting effects and are therefore widely applied in the food industry. Members of the Bifidobacterium genus were first identified from the human gastrointestinal tract and were then found to be widely distributed across various ecological niches. Although the genetic diversity of Bifidobacterium has been determined based on several marker genes or a few genomes, the global diversity and evolution scenario for the entire genus remain unresolved. The present study comparatively analyzed the genomes of 45 type strains. We built a robust genealogy for Bifidobacterium based on 402 core genes and defined its root according to the phylogeny of the tree of bacteria. Our results support that all human isolates are of younger lineages, and although species isolated from bees dominate the more ancient lineages, the bee was not necessarily the original host for bifidobacteria. Moreover, the species isolated from different hosts are enriched with specific gene sets, suggesting host-specific adaptation. Notably, bee-specific genes are strongly associated with respiratory metabolism and are potential in helping those bacteria adapt to the oxygen-rich gut environment in bees. This study provides a snapshot of the genetic diversity and evolution of Bifidobacterium, paving the way for future studies on the taxonomy and functional genomics of the genus.