Spirolactone-type and enmein-type derivatives as potential anti-cancer agents derived from oridonin.

Natural products (NPs) are always the important sources in the field of drug discovery, among which spirolactone-type and enmein-type compounds exhibit a wide range of biological activities, especially anti-tumor activity. Based on previous studies, the spirolactone-type and enmein-type compounds could be derived from natural oridonin (1) by several chemical reactions. Herein, a series of novel spirolactone-type and enmein-type derivatives with different aryl allyl ester substitutions at their C-14 hydroxyl group were designed and synthesized. The anti-tumor activity results showed that most of the compounds exhibited better anti-proliferative activities than parent compound oridonin, and the most potent compound had an IC50 value of 0.40 µM in K562 cells. Further mechanistic studies revealed that the optimal compound could arrest K562 cells at G2/M phase by inhibiting cdc-2, cdc-25c and cyclin B1 expression. In addition, the optimal compound induced apoptosis in K562 cells through increasing ROS production and depolarizing mitochondrial membrane potential. Collectively, these valuable results suggested that the most potent compound could be an anti-tumor agent candidate and is worthy of further investigation.

Identification and Validation of Quantitative Trait Loci Mapping for Spike-Layer Uniformity in Wheat.

Spike-layer uniformity (SLU), the consistency of the spike distribution in the vertical space, is an important trait. It directly affects the yield potential and appearance. Revealing the genetic basis of SLU will provide new insights into wheat improvement. To map the SLU-related quantitative trait loci (QTL), 300 recombinant inbred lines (RILs) that were derived from a cross between H461 and Chinese Spring were used in this study. The RILs and parents were tested in fields from two continuous years from two different pilots. Phenotypic analysis showed that H461 was more consistent in the vertical spatial distribution of the spike layer than in Chinese Spring. Based on inclusive composite interval mapping, four QTL were identified for SLU. There were two major QTL on chromosomes 2BL and 2DL and two minor QTL on chromosomes 1BS and 2BL that were identified. The additive effects of QSlu.sicau-1B, Qslu.sicau-2B-2, and QSlu.sicau-2D were all from the parent, H461. The major QTL, QSlu.sicau-2B-2 and QSlu.sicau-2D, were detected in each of the conducted trials. Based on the best linear unbiased prediction values, the two loci explained 23.97% and 15.98% of the phenotypic variation, respectively. Compared with previous studies, the two major loci were potentially novel and the two minor loci were overlapped. Based on the kompetitive allele-specific PCR (KASP) marker, the genetic effects for QSlu.sicau-2B-2 were validated in an additional RIL population. The genetic effects ranged from 26.65% to 32.56%, with an average value of 30.40%. In addition, QSlu.sicau-2B-2 showed a significant (p < 0.01) and positive influence on the spike length, spikelet number, and thousand kernel weight. The identified QTL and the developed KASP marker will be helpful for fine-mapping these loci, finally contributing to wheat breeding programs in a marker-assisted selection way.

Phenotypic and genetic variation in phosphorus-deficiency-tolerance traits in Chinese wheat landraces.

BACKGROUND: Phosphorus deficiency is a major limiting factors for affecting crop production globally. To understand the genetic variation of phosphorus-deficiency-tolerance, a total of 15 seedling traits were evaluated among 707 Chinese wheat landraces under application of phosphorus (AP) and non-application of phosphorus (NP). A total of 18,594 single-nucleotide polymorphisms and 38,678 diversity arrays technology sequencing markers were used to detect marker-trait associations under AP and NP. RESULTS: Top ten genotypes with extremely tolerance and bottommost ten genotypes with extremely sensitivity were selected from 707 Chinese wheat landraces for future breeding and genetic analysis. A total of 55 significant markers (81 marker-trait associations) for 13 traits by both CMLM and SUPER method. These were distributed on chromosomes 1A, 1B, 2A, 2B, 2D, 3A, 4B, 5A, 5B, 6A, 6B, 6D, 7A and 7B. Considering the linkage disequilibrium decay distance, 25 and 12 quantitative trait loci (QTL) were detected under AP and NP, respectively (9 QTL were specific to NP). CONCLUSIONS: The extremely tolerant landraces could be used for breeding phosphorus-deficiency-tolerant cultivars. The QTL could be useful in wheat breeding through marker-assisted selection. Our findings provide new insight into the genetic analysis of P-deficiency-tolerance, and will be helpful for breeding P-deficiency-tolerant cultivars.

Multi-Locus Genome-Wide Association Study of Four Yield-Related Traits in Chinese Wheat Landraces.

Wheat (Triticum aestivum L.) is one of the most important crops in the world. Here, four yield-related traits, namely, spike length, spikelets number, tillers number, and thousand-kernel weight, were evaluated in 272 Chinese wheat landraces in multiple environments. Five multi-locus genome-wide association studies (FASTmrEMMA, ISIS EN-BLASSO, mrMLM, pKWmEB, and pLARmEB) were performed using 172,711 single-nucleotide polymorphisms (SNPs) to identify yield-related quantitative trait loci (QTL). A total of 27 robust QTL were identified by more than three models. Nine of these QTL were consistent with those in previous studies. The remaining 18 QTL may be novel. We identified a major QTL, QTkw.sicau-4B, with up to 18.78% of phenotypic variation explained. The developed kompetitive allele-specific polymerase chain reaction marker for QTkw.sicau-4B was validated in two recombinant inbred line populations with an average phenotypic difference of 16.07%. After combined homologous function annotation and expression analysis, TraesCS4B01G272300 was the most likely candidate gene for QTkw.sicau-4B. Our findings provide new insights into the genetic basis of yield-related traits and offer valuable QTL to breed wheat cultivars via marker-assisted selection.

Genome-Wide Association Study of Kernel Traits in Aegilops tauschii.

Aegilops tauschii is the diploid progenitor of the D subgenome of hexaploid wheat (Triticum aestivum L.). Here, the phenotypic data of kernel length (KL), kernel width (KW), kernel volume (KV), kernel surface area (KSA), kernel width to length ratio (KWL), and hundred-kernel weight (HKW) for 223 A. tauschii accessions were gathered across three continuous years. Based on population structure analysis, 223 A. tauschii were divided into two subpopulations, namely T-group (mainly included A. tauschii ssp. tauschii accessions) and S-group (mainly included A. tauschii ssp. strangulata). Classifications based on cluster analysis were highly consistent with the population structure results. Meanwhile, the extent of linkage disequilibrium decay distance (r 2 = 0.5) was about 110 kb and 290 kb for T-group and S-group, respectively. Furthermore, a genome-wide association analysis was performed on these kernel traits using 6,723 single nucleotide polymorphism (SNP) markers. Sixty-six significant markers, distributed on all seven chromosomes, were identified using a mixed linear model explaining 4.82-13.36% of the phenotypic variations. Among them, 15, 28, 22, 14, 21, and 13 SNPs were identified for KL, KW, KV, KSA, KWL, and HKW, respectively. Moreover, six candidate genes that may control kernel traits were identified (AET2Gv20774800, AET4Gv20799000, AET5Gv20005900, AET5Gv20084100, AET7Gv20644900, and AET5Gv21111700). The transfer of beneficial genes from A. tauschii to wheat using marker-assisted selection will broaden the wheat D subgenome improve the efficiency of breeding.

A Genome-Wide Association Study of Coleoptile Length in Different Chinese Wheat Landraces.

From the perspective of wheat yield improvement, the coleoptile is vital for successful crop establishment, and long coleoptile lengths (CLs) are preferred in wheat-growing regions where deep planting is practiced. To determine the genetic basis of CL, we performed a genome-wide association study on a set of 707 Chinese wheat landraces using 18,594 single-nucleotide polymorphisms and 38,678 diversity array technology sequencing markers. We accordingly detected a total of 29 significant markers [-log10 (P) > 4.76] distributed on chromosomes 2B, 2D, 3A, 4A, 5A, 6A, 6B, 6D, and 7B. Based on linkage disequilibrium decay distance, we identified a total of 17 quantitative trait loci associated with CL, among which QCl.sicau-6B.2, located at 508.17-509.26 Mb on chromosome 6B, was recognized as a novel major locus. We subsequently developed a high-resolution melt marker for QCl.sicau-6B.2, which was validated in an F 2 : 3 population. Our findings provide important insights into the genetic mechanisms underlying coleoptile growth and could be applied to marker-assisted wheat selection.