If you are citing a reference for the first time in these legends, please include all new references in the Online Methods References section, and carry on the numbering from the main References section of the paper. Extended DataFig. 1 Alternative splicing site of the PHYC gene in xiaomi a, RNA-Seq reads of Jingu21. xiaomi genome sequences were used as reference genome. The blue vertical line shows the G-T mutation site. b, RNA-seq reads of xiaomi. The wrong splicing site was marked by a red arrow. Extended Data Fig. 2 Phenotypic and molecular characterization of the xiaomi-2 mutant a, Forty-day-old plants of Jingu21 (wild type, left) and xiaomi-2 (right) plants grown under natural long-day conditions. b, Heading date of Jingu21and xiaomi-2 under natural field conditions. The heading date of ≥ 20 plants was measured for each replicate (n = 3 biologically independent replicates, ≥ 102 in total). The bottom and top of boxes represent the first and third quartile, respectively. The middle line is the median and the whiskers represent the maximum and minimum values. Statistical analysis was performed using two-tailed Wilcoxon rank-sum test. c, A mature small-sized xiaomi-2 plant (right) compared to Jingu21 (left), at the 68th day in field. d, Plant height of Jingu21 and xiaomi-2 under natural field conditions. The plant height of ≥ 23 plants was measured for each replicate (n = 3 biologically independent replicates, ≥ 83 in total). e, Molecular charicterization of xiaomi-2. Exons and introns are denoted by filled boxes and lines, respectively. P2F and P2R represent a pair of primers used to amplify the fragments harboring the mutation site from the segregating M3 individuals (Primer sequences are listed in SupplementaryTable 3). c, Structure of PHYC and its mutation version deduced according to mutations in xiaomi-2. Scale bars, 10 cm in a and c. Extended Data Fig. 3 Sequence alignment of the GAF domain of PHYC in foxtail millet and its homologs software. Red box indicates the conserved residue Leu across all listed species that is substituted with His in xiaomi-2, demonstrating its functional importance for PHYC. Accession numbers for the aligned sequences: Arabidopsis thaliana NP_198433, Brachypodium distachyon XP_003559446, Brassica napus XP_013680236, Ipomoea nil XP_019162785, Oryza sativa AAF66603, Panicum miliaceum, RLN42126, Solanum lycopersicum NP_001307446, Sorghum bicolor XP_002466441, Triticum aestivum AAU06208, Vitis vinifera ACC6096 and Zea mays XP_008665426. PHYC protein in Jingu21 is presented as for Setaria italica (Si9G09200).Extended Data Fig. 4 Hi-C interaction matrices show the pairwise correlations between ordered scaffolds along the 9 pseudomolecules correlation. in T1 transgenic seeds as visualized for GFP expression or multiple (c) T-DNA insertions were scanned with a dissection microscope equipped with UV light. All experiments were performed for eight independent biological repeats, and similar results were obtained. Scale bars, 2 mm. Extended Data Fig. 6 PCR confirmation of the site-specif...

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We studied the size dependence of the ferroelectric domain structure in unique free-standing PbTiO 3 thin film, composed of grains 60-1000 nm in size, with transmission-electron microscopy. With such samples, we showed that the apparent dependence of electrical properties on the thickness of polycrystalline thin films stems from their grain-size dependence. We found that a domain-structure transition, from predominantly multidomain to predominantly single domain occurs at a grain size of ϳ150 nm ͑corresponding to a thickness 200-300 nm͒. Based on these experimental results, the drastic change of coercive field and dielectric permittivity below a thickness 200-300 nm was reasonably explained as resulting from a domain-structure transition.

BackgroundInterleukin-8 (IL-8) plays a vital role in the invasion and metastasis of hepatocellular carcinoma (HCC), and is closely associated with poor prognosis of HCC patients. Integrin αvβ3, a member of the integrin family, has been reported to be overexpressed in cancer tissues and mediate the invasion and metastasis of HCC cells. However, the relationship between IL-8 and integrin αvβ3 in HCC and the underlying mechanism of IL-8 and integrin αvβ3 in the invasion of HCC remains unclear.MethodsThe expression of IL-8, integrin αv and integrin β3 in HCC cells and tissues was detected by quantitative real-time PCR, Western blot and immunohistochemistry. Transwell assay and Western blot was used to detect the invasiveness, the expression of integrin β3 and the activation of PI3K/Akt pathway of HCC cells pretreated with IL-8 knockdown or exogenous IL-8.ResultsIL-8, integrin αv and integrin β3 were overexpressed in highly metastatic HCC cell lines compared with low metastatic cell lines. There was a positive correlation between integrin β3 and IL-8 expression in HCC tissues. IL-8 siRNA transfection reduced HCC cell invasion and the levels of integrin β3, p-PI3K and p-Akt. IL-8 induced HCC cell invasion and integrin β3 expression was significantly inhibited by transfection with CXCR1 siRNA or CXCR2 siRNA. When we stimulated HCC cells with exogenous IL-8, cell invasion and the levels of integrin β3, p-PI3K, and p-Akt increased, which could be effectively reversed by adding PI3K inhibitor LY294002.ConclusionsOur results suggest that IL-8 promotes integrin β3 upregulation and the invasion of HCC cells through activation of the PI3K/Akt pathway. The IL-8/CXCR1/CXCR2/PI3K/Akt/integrin β3 axis may serve as a potential treatment target for patients with HCC.

The zinc-fingers and homeoboxes 2 (ZHX2) protein was shown previously to be involved in postnatal repression of α-fetoprotein (AFP) in mice. More recently, loss of ZHX2 expression was often found in human hepatcellular carcinoma (HCC), where AFP is frequently reactivated. Using HepG2 and HepG2.2.15, which express high AFP levels, we show that ZHX2 overexpression significantly decreases of AFP secretion in a dose dependent manner. Furthermore, using LO2 and SMMC7721 cells, which express low AFP levels, we use siRNA inhibition to show that AFP is de-repressed when ZHX2 levels are reduced. This represents the first direct evidence that ZHX2 represses AFP. Co-transfections of ZHX2 and AFP-luciferase reporter genes demonstrate ZHX2 repression is governed by the AFP promoter and requires intact HNF1 binding sites. These data support the idea that ZHX2 contributes to AFP repression in the liver after birth and may also be involved in AFP reactivation in liver cancer.

Several studies have revealed that MFG-E8 (milk fat globule-epidermal growth factor 8) is related to tumour development and progression. However, the relationship between MFG-E8 expression and metastasis in colorectal cancer patients and the role of MFG-E8 in colorectal cancer invasion and progression remain unknown. In this study, we performed immunohistochemistry and quantitative real-time polymerase chain reaction to assess MFG-E8 expression in colorectal cancer and adjacent non-cancerous tissues. Colorectal cancer RNAseq data from The Cancer Genome Atlas project were downloaded and MFG-E8 expression was analysed. Gene set enrichment analysis was performed for gene ontology and pathway analysis associated with MFG-E8 expression. For in vitro studies, we used lentivirus-mediated MFG-E8 RNA interference and commercialized recombinant human MFG-E8 to investigate its role in colorectal cancer cell growth, migration and invasion. It seems that MFG-E8 was overexpressed in advanced colorectal cancer tissues compared with early-stage colorectal cancer tissues and adjacent non-cancerous tissues. Correlation analysis revealed that MFG-E8 expression was significantly related to plasma membrane invasion, lymph node metastasis, distant metastasis and tumour-node-metastasis stage. Survival analysis revealed that high MFG-E8 expression predicted a poorer prognosis than low MFG-E8 expression group both in our colorectal cancer cohort and The Cancer Genome Atlas colorectal cancer cohort. In vitro study suggested that MFG-E8 knockdown can suppress the growth of colorectal cancer cells without affecting the expression of the proliferation-related gene Ki67. MFG-E8 knockdown also suppressed colorectal cancer cell migration and invasion, a change accompanied by MMP-2 and MMP-9 downregulation. Moreover, MFG-E8 knockdown induced a shift from mesenchymal makers to epithelial makers, while pretreatment with rhMFG-E8 had the opposite effect. The effect of MFG-E8 on colorectal cancer cell migration, invasion and epithelial-to-mesenchymal was partially dependent on the PI3K/AKT signalling pathway. These findings provide a better understanding of the molecular mechanism underlying colorectal cancer progression and suggest a predictive role for MFG-E8 in colorectal cancer metastasis and prognosis.

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Ovarian carcinoma is a lethal gynecological malignancy. Women with ovarian cancer (OC) are highly recurrent and typically diagnosed at late stage. Ten-eleven translocation protein 3 (TET3) belongs to the family of ten-eleven translocations (TETs) which induce DNA demethylation and gene regulation in epigenetic level by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Previous studies indicated that TET3 is overexpressed in ovarian cancer tissues. However, the clinic-pathological functions and prognostic values of TET3 remain unclear. Here we performed an integrative study to identify the role of TET3 by bioinformatics analysis. The TET3 expression in ovarian cancer was assessed with Oncomine database, and validated with TCGA and GTEx database. The correlation of TET3 gene alteration and clinic-pathological functions was addressed by integrative analysis of GEO datasets. Then we showed mainly TET3 gain and diploid but less deletion in ovarian cancer by copy number alteration (CNA) or mutation analysis with cBioPortal. Furthermore, by using Kaplan-Meier plotter (K-M plotter), we evaluated that high TET3 level was associated with poor survival in ovarian cancer patients, which was validated with analysis by PrognoScan database and gene differential analyses with TCGA and GTEx. This is the first study demonstrated that elevated expression of TET3 is associated with poor clinic-pathological functions, poor prognosis, wherein TET3, which presents epigenetic changes or methylation changes, might be served as a diagnostic marker or therapeutic target for ovarian cancer.