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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.