Knocking Down Gm16685 Decreases Liver Granuloma in Murine Schistosomiasis Japonica.

Long noncoding RNAs (lncRNAs) can regulate key genes and pathways in liver disease development. Moreover, macrophages are speculated to play an important role in regulating granulomatous inflammation during schistosomiasis. However, the role of lncRNAs in the formation of liver granulomas by influencing the polarization of macrophages in Schistosoma japonicum infection is unclear. Our study aimed to determine whether lncRNAs can play a role in S. japonicum-induced hepatic egg granulomas and elucidate their effect on macrophages. We established S. japonicum infection models and screened the target lncRNA Gm16685 highly expressed in schistosomiasis mice using high-throughput sequencing. Hematoxylin and eosin staining revealed that the knockdown of Gm16685 reduced the area of egg granulomas. Moreover, M1 macrophage factor genes were significantly downregulated in Gm16685 knockdown livers. Meanwhile, M2 macrophage factor genes were significantly upregulated, which was consistent with the protein detection results. Hepatocytes, hepatic stellate cells, and macrophages were isolated from mouse models infected with S. japonicum, with Gm16685 being significantly upregulated in macrophages. Moreover, the knockdown of Gm16685 in RAW264.7 cells revealed similar results to in liver tissue. RNA fluorescence in situ hybridization (FISH) and nucleocytoplasmic separation experiments revealed that Gm16685 was predominantly localized in the cytoplasm of cells. We found that miR-205-5p was upregulated after Gm16685 was knocked down. After overexpression of miR-205-5p, the expression of Gm16685 and inflammatory factors was significantly downregulated. These results indicate that Gm16685 can participate in the pathogenesis of hepatic disease in schistosomiasis and promote M1 macrophage polarization by regulating miR-205-5p. Thus, our study may provide a new target for schistosomiasis japonica treatment.

Armadillo repeat only protein GS10 negatively regulates brassinosteroid signaling to control rice grain size.

Grain yield and grain quality are major determinants in modern breeding controlled by many quantitative traits loci (QTLs) in rice (Oryza sativa). However, the mechanisms underlying grain shape and quality are poorly understood. Here, we characterize a QTL for grain size and grain quality via map-based cloning from wild rice (W1943), GS10 (Grain Size on Chromosome 10), which encodes a protein with 6 tandem armadillo repeats. The null mutant gs10 shows slender and narrow grains with altered cell size, which has a pleiotropic effect on other agronomical traits. Functional analysis reveals that GS10 interacts with TUD1 (Taihu Dwarf1) and is epistatic to OsGSK2 (glycogen synthase kinase 2) through regulating grain shape and lamina joint inclination, indicating it is negatively involved in brassinosteroid (BR) signaling. Pyramiding gs10 and the grain size gene GW5 into cultivar GLA4 substantially improved grain shape and appearance quality. Natural variation analysis revealed that gs10 from the wild rice Oryza rufipogon W1943 is a rare allele across the rice population. Collectively, these findings advance our understanding of the underlying mechanism of grain shape and provide the beneficial allele of gs10 for future rice breeding and genetic improvement.

A retrotransposon insertion in MUTL-HOMOLOG 1 affects wild rice seed set and cultivated rice crossover rate.

Wild rice (Oryza rufipogon) has a lower panicle seed setting rate (PSSR) and gamete fertility than domesticated rice (Oryza sativa), but the genetic mechanisms of this phenomenon remain unknown. Here, we cloned a null allele of OsMLH1, an ortholog of MutL-homolog 1 to yeast and mammals, from wild rice O. rufipogon W1943 and revealed a 5.4-kb retrotransposon insertion in OsMLH1 is responsible for the low PSSR in wild rice. In contrast to the wild-type, a near isogenic line NIL-mlh1 exhibits defective crossover (CO) formation during meiosis, resulting in reduced pollen viability, partial embryo lethality, and low PSSR. Except for the mutant of mismatch repair gene postmeiotic segregation 1 (Ospms1), all other MutL mutants from O. sativa indica subspecies displayed male and female semi-sterility similar to NIL-mlh1, but less severe than those from O. sativa japonica subspecies. MLH1 and MLH3 did not contribute in an additive fashion to fertility. Two types of MutL heterodimers, MLH1-PMS1 and MLH1-MLH3, were identified in rice, but only the latter functions in promoting meiotic CO formation. Compared to japonica varieties, indica cultivars had greater numbers of CO events per meiosis. Our results suggest that low fertility in wild rice may be caused by different gene defects, and indica and japonica subspecies have substantially different CO rates responsible for the discrepancy between the fertility of mlh1 and mlh3 mutants.

JQ-1 ameliorates schistosomiasis liver granuloma in mice by suppressing male and female reproductive systems and egg development of Schistosoma japonicum.

Schistosomiasis is a serious and widespread parasitic disease caused by infection with Schistosoma. Because the parasite's eggs are primarily responsible for schistosomiasis dissemination and pathogenesis, inhibiting egg production is a potential approach to control the spread and severity of the disease. The bromodomain and extra-terminal (BET) proteins represent promising targets for the development of epigenetic drugs against Schistosoma. JQ-1 is a selective inhibitor of the BET protein family. In the present study, JQ-1 was applied to S. japonicum in vitro. By using laser confocal scanning microscopy and EdU incorporation assays, we showed that application of JQ-1 to worms in vitro affected egg laying and the development of both the male and female reproductive systems. JQ-1 also inhibited the expression of the reproductive-related genes SjPlk1 and SjNanos1 in S. japonicum. Mice infected with S. japonicum were treated with JQ-1 during egg granuloma formation. JQ-1 treatment significantly reduced the size of the liver granulomas and levels of serum alanine aminotransferase and aspartate aminotransferase in mice and suppressed both egg laying and the development of male and female S. japonicum reproductive systems in vivo. Moreover, the mRNA expression levels of some proinflammatory cytokines were decreased in the parasites. Our findings suggest that JQ-1 treatment attenuates S. japonicum egg-induced hepatic granuloma due at least in part to suppressing the development of the reproductive system and egg production of S. japonicum. These findings further suggest that JQ-1 or other BET inhibitors warrant additional study as a new approach for the treatment or prevention of schistosomiasis.

Cytoplasmic and nuclear genome variations of rice hybrids and their parents inform the trajectory and strategy of hybrid rice breeding.

The male sterility (MS) line is a prerequisite for efficient production of hybrid seeds in rice, a self-pollinating species. MS line breeding is pivotal for hybrid rice improvement. Understanding the historical breeding trajectory will help to improve hybrid rice breeding strategies. Maternally inherited cytoplasm is an appropriate tool for phylogenetic reconstruction and pedigree tracing in rice hybrids. In this study, we analyzed the cytoplasmic genomes of 1495 elite hybrid rice varieties and identified five major types of cytoplasm, which correspond to different hybrid production systems. As the cytoplasm donors for hybrids, 461 MS lines were also divided into five major types based on cytoplasmic and nuclear genomic architecture. Specific core accessions cooperating with different fertility-associated genes drove the sequence divergence of MS lines. Dozens to hundreds of convergent and divergent selective sweeps spanning several agronomic trait-associated genes were identified among different types of MS lines. We further analyzed the cross patterns between different types of MS lines and their corresponding restorers. This study systematically analyzed the cytoplasmic genomes of rice hybrids revealed their relationships with nuclear genomes of MS lines, and illustrated the trajectory of hybrid rice breeding and the strategies for breeding different types of MS lines providing new insights for future improvement of hybrid rice.