Search

Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer’s disease (AD) progression, yet the role of gut microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression. Using AD mouse models, we discovered that, during AD progression, the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine, which stimulates the differentiation and proliferation of pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated peripheral Th1 immune cells are associated with the M1 microglia activation, contributing to AD-associated neuroinflammation. Importantly, the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment (MCI) due to AD. Furthermore, GV-971, a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China, suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation, harnesses neuroinflammation and reverses the cognition impairment. Together, our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota.

Background Rice blast caused by Magnaporthe oryzae is one of the most widespread biotic constraints that threaten rice production. Using major resistance genes for rice blast resistance improvement is considered to be an efficient and technically feasible approach to achieve optimal grain yield. Results We report here the introgression of the broad-spectrum blast resistance gene Pi2 into the genetic background of an elite PTGMS line, Feng39S, for enhancing it and its derived hybrid blast resistance through marker-assisted backcrossing (MABC) coupled with genomics-based background selection. Two PTGMS lines, designated as DB16206–34 and DB16206–38, stacking homozygous Pi2 were selected, and their genetic background had recurrent parent genome recovery of 99.67% detected by the SNP array RICE6K. DB16206–34 and DB16206–38 had high resistance frequency, with an average of 94.7%, when infected with 57 blast isolates over 2 years, and the resistance frequency of their derived hybrids ranged from 68.2% to 95.5% under inoculation of 22 blast isolates. The evaluation of results under natural blast epidemic field conditions showed that the selected PTGMS lines and their derived hybrids were resistant against leaf and neck blast. The characterizations of the critical temperature point of fertility-sterility alternation of the selected PTGMS lines, yield, main agronomic traits, and rice quality of the selected PTGMS lines and their hybrids were identical to those of the recurrent parent and its hybrids. DB16206–34/9311 or DB16206–38/9311 can be used as a blast-resistant version to replace the popular hybrid Fengliangyou 4. Likewise, DB16206–34/FXH No.1 or DB16206–38/FXH No.1 can also be used as a blast-resistant version to replace another popular hybrid Fengliangyou Xiang 1. Conclusions Our evaluation is the first successful case to apply MABC with genomics-based background selection to improve the blast resistance of PTGMS lines for two-line hybrid rice breeding.

Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease (AD) progression, yet the role of gut microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression. Using AD mouse models, we discovered that, during AD progression, the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine, which stimulates the differentiation and proliferation of pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated peripheral Th1 immune cells are associated with the M1 microglia activation, contributing to AD-associated neuroinflammation. Importantly, the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment (MCI) due to AD. Furthermore, GV-971, a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China, suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation, harnesses neuroinflammation and reverses the cognition impairment. Together, our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota.

Background Breeding two-line hybrid rice with disease resistance is an effective approach to stabilize rice yield in commercial rice production of China. Results We improved the blast and bacterial blight resistance of Guangzhan63-4S, an elite photoperiod- and thermo-sensitive male sterile (P/TGMS) line widely used in two-line hybrid rice, by introducing the R genes Pi2 and Xa7 conferring resistance to rice blast and bacterial blight, respectively. Through the backcrossing and gene pyramiding breeding coupled with molecular marker-assisted selection, a new P/TGMS line Hua1228S carrying Pi2, Xa7, and tms5 was developed. Based on 200,000 SNP markers by next-generation sequencing, Hua1228S covered 87.6% of the recurrent genome, as well as 4.5% of the donor genome from VE6219 and 7.9% from YR7029–39. When infected with seven tested Xanthomonas oryzae pv. oryzae strains, Hua1228S conferred high resistance (0 level) to six bacterial blight strains. Moreover, Hua1228S showed broad-spectrum resistance to rice blast isolates with a high resistance frequency of 90.91%. High levels of resistance to leaf blast and neck blast were observed under heavy disease pressure in natural field. Importantly, Hua1228S showed identical fertility-sterility alteration pattern to Guangzhan63-4S. Thus, two hybrid combinations Hua Liangyou 2821 and Hua Liangyou 284 derived from Hua1228S exhibited enhanced resistance and higher yield compared with the control variety Feng Liangyou 4. Conclusions These results indicate that Hua1228S has tremendous potentiality to increase and stabilize the rice yield, through the introgression of two R genes by marker-assisted selection strategy. Electronic supplementary material The online version of this article (10.1186/s12284-018-0203-8) contains supplementary material, which is available to authorized users.

The two-line system of hybrid rice seed production based on thermo-sensitive genic male-sterile (TGMS) lines is much more cost-effective, simple and efficient than the three-line system with cytoplasmic male sterility. In this study, we report the introgression of a rice blast resistance gene Pi2 from VE6219 and a bacterial blight (BB) resistance gene Xa23 from HBQ810 into Guangzhan63-4S (GZ63-4S), an elite TGMS rice line, through marker-assisted pyramiding, leading to the development of Hua1015S, a blast- and BB-resistant pyramided line. The newly developed TGMS line Hua1015S and its derived hybrids showed resistance to rice blast and BB. Hua1015S had a similar critical temperature point of fertility–sterility alteration to GZ63-4S and similar key agronomic and grain quality traits. However, Hua1015S gave higher hybrid seed yields on account of increased outcrossing rates due to better floral traits, e.g. spikelet dehiscence, angle of glume opening, and stigma exsertion. The newly developed TGMS parental line Hua1015S with Pi2 and Xa23 is currently being utilized for heterosis breeding of broad-spectrum blast- and BB-resistant two-line rice hybrids and as an improved disease donor source for further TGMS parental line improvement.

New anticancer drug development is an expensive and time consuming process, which typically can take more than 10 years and cost over a billion dollars. Although a majority of late discovery drug candidates demonstrate potency in preclinical models, most will ultimately fail to achieve efficacy in clinical trials. While recent strides have been made to improve preclinical models, the continued widespread use of traditional models creates translational challenges during clinical development. An intrinsic challenge for drug developers is to close the gap between preclinical modeling and translational efficiency for patients. Accurately modeling core attributes of the human tumor microenvironment (TME) in preclinical models is key for identifying novel targets, lowering toxicity and improving translational success. Even for advanced patient-derived xenograft (PDX) in vivo models, the cytokines generated by murine stromal cells fail to replicate many important paracrine networks, which can mislead preclinical pharmacology outcome data. To address this gap, we have begun to establish and characterize nearly 1,000 novel patient tumor samples, spanning over a dozen cancer indications, into robust human TME-restored 3D cell culture models and humanized patient derived xenograft models. Our goal is to improve overall patient-derived tumor model initiation success rates and subsequent translational pharmacology. Citation Format: Jing Zhang, Dabing Yang, Huilin Wang, Qiong Song, Hui Li, JP Shaw, Tianjing Deng. Novel tumor microenvironment (TME) restored 3D cell culture model and humanized patient-derived xenograft model for cancer research and drug evaluation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4261.

Combined with integrated management function of three data libraries ((DEM, DOM and DLG) and based on the digital photogrammetry workstation (DPW) such as the JX-4A three-dimensional code data collection, GIS data, AutoCAD data, the three-dimensional model of the city was built. The urban landscape three-dimensional system was developed using VC++ and OpenGL, which was used in data collection and digital modeling of urban landscape, and was applied to many fields such as urban landscape design, landscape planning, landscape evaluation and urban landscape facility enquiry etc. The three-dimensional visualization application system was set up realizing the three-dimensional visualization operation and analysis to the application system.

The paper constructed the mine ventilation network model using the powerful function of attributes management, display visually and spatial analysis of GIS based on the character study of GIS and mine ventilation network. The mine ventilation network model we put forward in this paper is a COM-based extension of the Geo-network of ArcInfo. In mine ventilation network model, specified result can be obtained by defining weigh values for attribute fields as the constraint condition. It is of great importance for mines to determine the best rescue and leaving route by mine ventilation network route analysis, node analysis and loop analysis when mine accident happens. By the mine ventilation network model we put forward in this paper, the best rescue and leaving route can be implemented in a short time. The research achievement is used successfully in ShiGejie mine, Shanxi Province of China. The application result shows the feasibility of the study achievement

Wetland is one of the most important ecosystems and plays an important role in environment stabilization and species preserving. Fujian province is a coastal province of China possessing a considerable portion of wetland. In this paper, based on landscape ecology, remote sensing and geographical information system technologies, the dynamic change of wetlands in Fujian province of China is analyzed. ETM+ data of 1996 and 2002 that cover the study area were acquired. A wetland map of study area published in 1990 was also used. The images were preprocessed by geometric correction and geo-reference using the digital map, and were free of clouds. Then radiometric correction was done to make the image statistics and histograms from different time periods similar and comparable for the study area. Thus the wetlands in different times were identified by the images. The resultants were further analyzed jointly using ARC/INFO. The analysis result indicated that the wetlands in Fujian province mainly distributes around the bays along coast. In backland there were few wetlands except for some regions around a few reservoirs. The area of wetlands decreased greatly from 1990 to 2002, especially from 1990 to 1996. Since 1996 the decrease speed of wetland area had become slow. The result also indicated that the fragmentation of wetland landscape was evident in these years. The number and density of patch of wetlands had increased largely. The spatial distribution feature of wetland was studied by fractal theory. The fractal dimensional values were calculated respectively and they changed a lot. This means that the shape of wetland landscape had transformed. The wetlands around Jiulong river delta and Quanzhou coast were the main area where the area of wetland decreased evidently. In these areas, economic activities are the main reason for the decrease of wetland area such as the expansion of buildings, roads, farmland and so on