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Beneficial microorganisms can protect crop from phytopathogens, and modify rhizosphere microbiome. However, it is not well understood whether or how do rhizosphere microorganisms which respond to bio-agents contribute to disease suppression. Bacillus velezensis BER1 and tomato bacterial wilt caused by Ralstonia solanacearum were selected as models to disentangle the interactions and mechanisms in the rhizosphere. B. velezensis BER1 greatly suppressed tomato bacterial wilt by over 49.0%, reduced R. solanacearum colonization in the rhizosphere by 36.3%, and significantly enriched two Flavobacterium ASVs (1357 and 2401). A novel colony Loop-Mediated Isothermal Amplification (LAMP) assay system was developed to screen out Flavobacterium from tomato rhizosphere bacterial isolates. In vitro tests revealed that co-cultivating BER1 with Flavobacterium C45 increased biofilm formation by 18.6%. Climate chamber experiment further revealed that Flavobacterium C45 improved the control efficiency of BER1 on tomato bacterial wilt by 46.0%, decreased the colonization of R. solanacearum in the rhizosphere by 43.1% and elevated the transcription of plant defense gene PR1α in tomato by 45.4%. In summary, Flavobacterium C45 boosted the ability of B. velezensis BER1 to prevent bacterial wilt and the colonization of R. solanacearum, highlighting the importance of helper bacteria on elevating the efficiency of biological control.

Supplementary Table 1 XLS file 22K, Tumors and reference tissues for methylation microarray analysis

Supplementary Figure 1 - PDF file 1233K, Supplemental Figure 1: Representative array comparative genomic hybridization (aCGH) results of genomic copy number near-normal GIST (left column, n=5) and genomic copy number abnormal GIST (right column, n=5) (Agilent 180K catalogue assay)

Supplementary Table 2 XLSX file 490K, Illumina GoldenGate Methylation Standard Cancer Panel I Target CpG Annotations and differential methylation significance values for group comparisons listed in Table

Legends for all included Supplementary Figures

Heat map of cell cycle gene expression. Gene expression was normalized and compared between the primary MTC, metastasis one, and metastasis two lesions from the whole transcriptome RNA-seq data. Purple indicates lower and yellow indicates higher expression. Values to generate colors are z-scores across each genes' relative transcript levels [log2(FPKM)].

Weight-for-age and height-for-age growth curves. Male patient weights (A), heights (B) and female patient weights (C), and heights (D) were monitored during the follow up period. Patient weight-for-age and height-for-age values were compared to U.S. Center for Disease Control reference growth curves.

Doubling time of calcitonin and CEA for patient #12 was suggestive of progressive disease. Patient #12 experienced best response 434 days after starting vandetanib, with stable lesions in the thyroid bed (showed on T2-weighted MRI of the neck, A) and the mediastinum (showed on CT of the chest, B). In August 2016, the sum of longest diameter (per RECIST) of target lesions was consistent with SD (C,D) (note that not all target lesions are shown). Biomarker response in the two years prior (E) showed CEA doubling time 1.2 years (F) and calcitonin doubling time 1.67 years (G). Patient #12 was confirmed to have PD via RECIST February 2017.

Purpose: Vandetanib is well-tolerated in patients with advanced medullary thyroid carcinoma (MTC). Long-term outcomes and mechanisms of MTC progression have not been reported previously.Experimental Design: We monitored toxicities and disease status in patients taking vandetanib for hereditary, advanced MTC. Tumor samples were analyzed for molecular mechanisms of disease progression.Results: Seventeen patients [8 male, age 13 (9–17)* years] enrolled; 16 had a RET p.Met918Thr germline mutation. The duration of vandetanib therapy was 6.1 (0.1–9.7+)* years with treatment ongoing in 9 patients. Best response was partial response in 10, stable disease in 6, and progressive disease in one patient. Duration of response was 7.4 (0.6–8.7+)* and 4.9 (0.6–7.8+)* years in patients with PR and SD, respectively. Six patients died 2.0 (0.4–5.7)* years after progression. Median progression-free survival (PFS) was 6.7 years [95% confidence interval (CI): 2.3 years–undefined] and 5-year overall survival (OS) was 88.2% (95% CI: 60.6%–96.9%). Of 16 patients with a RET p.Met918Thr mutation, progression-free survival was 6.7 years (95% CI: 3.1–undefined) and 5-year overall survival was 93.8% (95% CI: 63.2%–99.1%). No patients terminated treatment because of toxicity. DNA sequencing of tissue samples (n = 11) identified an increase in copy number alterations across the genome as a potential mechanism of drug resistance [*median (range)].Conclusions: This study demonstrates that vandetanib is safe and results in sustained responses in children and adolescents with hereditary MTC. Our preliminary molecular data suggest that an increase in copy number abnormalities may be associated with tumor progression in hereditary MTC patients treated with vandetanib. Clin Cancer Res; 24(4); 753–65. ©2017 AACR.

Doubling time of calcitonin and CEA during vandetanib therapy. Calcitonin and CEA slopes and doubling times were calculated from the change during the initial four months of vandetanib (A,B), from values the year before experiencing PD or the data cutoff (C,D) and in patients that experienced progressive disease (E).

Patients #2, #5, #10, #11, #13, #15, and #16 experienced durable SD or PR during the follow up period. Calcitonin and CEA are shown as percent change from baseline at the start of vandetanib therapy (left y-axis). Tumor size is the sum of longest diameter of lesions per RECISTv1.0 (right y-axis).

Nucleoporin 98 (NUP98) fusion genes and FMS-related tyrosine kinase 3 gene (FLT3) internal tandem duplications (ITDs) are recurrent events in patients with acute myeloid leukemia (AML). The NUP98::NSD1 fusion, which joins the amino terminal portion of NUP98 to the carboxy terminal portion of NSD1 (Nuclear receptor-binding SET Domain 1) is the most common NUP98 fusion in human AML. AML patients with NUP98::NSD1 fusion typically also have a FLT3-ITD mutation, and the combination of these two oncoproteins results in a poor prognosis. We established NUP98::NSD1 transgenic mice as an in vivo model. Although the penetrance of AML in mice that expressed a NUP98::NSD1 fusion was low, the incidence of AML increased dramatically when accompanied by a FLT3-ITD mutation. Gene expression profiling showed that murine NUP98::NSD1/FLT3-ITD AML were myelomonocytic, with an expression profile similar to human NUP98::NSD1 AML. Also similar to human AML, the wild type Flt3 allele was frequently lost in murine NUP98::NSD1/FLT3-ITD AML. Whole exome sequencing of NUP98::NSD1/FLT3-ITD AML revealed few Tier 1 somatic mutations, suggesting that the NUP98::NSD1 fusion protein and FLT3-ITD may be sufficient for leukemogenesis. This study demonstrates that the NUP98::NSD1 fusion gene is leukemogenic in vivo, and provides a model for pre-clinical studies.

An allene oxide cyclase 4, GmAOC4 , was determined by GWAS and RT-PCR to be significantly associated with seed germination in soybean, and regulates seed germination by promoting more JA accumulation. The seed germination phase is a critical component of the plant lifecycle, and a better understanding of the mechanism behind seed germination in soybeans is needed. We used a genome-wide association study (GWAS) to detect a GWAS signal on chromosome 18. In this GWAS signal, SNP S18_56189166 was located within the 3’untranslated region of Glyma.18G280900, which encodes allene oxide cyclase 4 (named GmAOC4). Analysis of real-time PCR demonstrated that expression levels of GmAOC4 in the low-germination variety (KF, carrying SNP S18_56189166-T) were higher than in the high-germination variety (NN, carrying SNP S18_56189166-C). In these two varieties, KF showed a higher JA concentration than NN at 0 and 24 h after imbibition. Moreover, the overexpression of GmAOC4 led to an increase in the concentration of jasmonic acid (JA) in soybean hairy roots and Arabidopsis thaliana. Furthermore, it was found that GmAOC4-OE lines showed less seed germination than the wild type (WT) under normal conditions in Arabidopsis. After 7 days of ABA treatment, transgenic lines exhibited lower seed germination and higher expression levels of AtABI5 compared with WT, indicating that the overexpression of GmAOC4 resulted in hypersensitivity to ABA. Our findings demonstrate that GmAOC4, which promotes more JA accumulation, helps to regulate seed germination in soybeans.

Plant annexins are a kind of conserved Ca2+-dependent phospholipid-binding proteins which are involved in plant growth, development and stress tolerance. Radish is an economically important annual or biennial root vegetable crop worldwide. However, the genome-wide characterization of annexin (RsANN) gene family remain largely unexplored in radish. In this study, a comprehensive identification of annexin gene family was performed at the whole genome level in radish. In total, ten RsANN genes were identified, and these putative RsANN proteins shared typical characteristics of the annexin family proteins. Phylogenetic analysis showed that the RsANNs together with annexin from Arabidopsis and rice were clustered into five groups with shared similar motif patterns. Chromosomal localization showed that these ten RsANN genes were distributed on six chromosomes (R3-R8) of radish. Several cis-elements involved in abiotic stress response were identified in the promoter regions of RsANN genes. Expression profile analysis indicated that the RsANN genes exhibited tissue-specific patterns at different growth stages and tissues. The Real-time quantitative PCR (RT-qPCR) revealed that the expression of most RsANN genes was induced under various abiotic stresses including heat, drought, salinity, oxidization and ABA stress. In addition, stress assays showed that overexpression of RsANN1a improved plant’s growth and heat tolerance, while artificial microRNAs (amiRNA)-mediated knockdown of RsANN1a caused dramatically decreased survival ratio of Arabidopsis plants. These findings not only demonstrate that RsANN1a might play a critical role in the heat stress response of radish, but also facilitate clarifying the molecular mechanism of RsANN genes in regulating the biological process governing plant growth and development.

Plant annexins are a kind of conserved Ca(2+)-dependent phospholipid-binding proteins which are involved in plant growth, development and stress tolerance. Radish is an economically important annual or biennial root vegetable crop worldwide. However, the genome-wide characterization of annexin (RsANN) gene family remain largely unexplored in radish. In this study, a comprehensive identification of annexin gene family was performed at the whole genome level in radish. In total, ten RsANN genes were identified, and these putative RsANN proteins shared typical characteristics of the annexin family proteins. Phylogenetic analysis showed that the RsANNs together with annexin from Arabidopsis and rice were clustered into five groups with shared similar motif patterns. Chromosomal localization showed that these ten RsANN genes were distributed on six chromosomes (R3-R8) of radish. Several cis-elements involved in abiotic stress response were identified in the promoter regions of RsANN genes. Expression profile analysis indicated that the RsANN genes exhibited tissue-specific patterns at different growth stages and tissues. The Real-time quantitative PCR (RT-qPCR) revealed that the expression of most RsANN genes was induced under various abiotic stresses including heat, drought, salinity, oxidization and ABA stress. In addition, stress assays showed that overexpression of RsANN1a improved plant’s growth and heat tolerance, while artificial microRNAs (amiRNA)-mediated knockdown of RsANN1a caused dramatically decreased survival ratio of Arabidopsis plants. These findings not only demonstrate that RsANN1a might play a critical role in the heat stress response of radish, but also facilitate clarifying the molecular mechanism of RsANN genes in regulating the biological process governing plant growth and development. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01056-5.

Vascular smooth muscle cell (SMC) phenotypic modulation contributes to the development of restenosis. A sorafenib-eluting stent was specifically designed to target SMC phenotypic modulation to inhibit in-stent restenosis in the present study. SMC contractile protein from the freshly isolated rat aorta was expressed at a high level, but its expression was dramatically reduced after SMCs were cultured in 10% FBS for 1 wk. After sorafenib treatment, SMC contractile protein expression was markedly upregulated. We further observed that Yes-associated protein (YAP) expression was attenuated after sorafenib treatment in a dose-dependent manner. Overexpression of YAP by lentivirus reversed the expression of sorafenib-induced SMC contractile protein and increased the expression of cyclin D. Mechanistically, sorafenib regulated the serum response factor-myocardin (SRF-Myocd) complex through competitive binding of YAP to Myocd and increased SRF binding to CArG-containing regions of SMC-specific contractile genes within intact chromatin, thereby controlling the activity of smooth muscle-specific gene transcription. In a rabbit carotid model, the sorafenib-eluting stent (SFES) dramatically inhibited in-stent restenosis and upregulated SMC contractile protein expression. Overexpression of YAP blocked the antirestenosis effect of SFES and repressed contractile smooth muscle-specific genes in vivo, indicating that SFES attenuated in-stent restenosis through YAP-mediated SMC phenotypic modulation. We demonstrated that SFES attenuated in-stent restenosis through YAP-mediated SMC phenotypic modulation. Targeting SMC phenotypic modulation by drug-eluting stent represents an attractive therapeutic approach for the treatment of occlusive vascular diseases. NEW & NOTEWORTHY In the present study, we demonstrated that sorafenib regulates smooth muscle cell (SMC) phenotypic modulation from a proliferative to a contractile state. Sorafenib induced a myocardin-serum response factor interaction and increased SMC contractile gene transcription through the Yes-associated protein pathway. Moreover, local delivery of sorafenib regulating SMC phenotypic modulation represents a promising strategy in the design of drug-eluting stents.

Purpose: To report a novel internal and external blood bypass method for cerebral protection during in situ triple-fenestrated stent-graft repair in the aortic arch. Technique: A method was devised to combine internal and external blood bypass circuits to preserve cerebral blood flow when all 3 supra-aortic branches are covered by the stent-graft. Long 14-F to 18-F introducers are placed retrogradely into the right and left common carotid arteries (CCAs). Smaller sheaths are placed antegradely into the internal carotid arteries (ICAs) bilaterally and into the right CCA introducer, which has had an aperture cut into it for flow to pass into the smaller sheath. The right CCA introducer is positioned in the ascending aorta to supply the innominate artery; the smaller sheath in the right CCA introducer is positioned at the aperture. The small sheath in the right CCA is connected to the left ICA sheath, and the left CCA fenestration is made and stented. The left ICA sheath is connected to the right ICA sheath, and the right CCA introducer is pulled back to the origin of the innominate artery and the smaller sheath removed. The fenestrations for the innominate and left subclavian arteries are opened sequentially. In 8 patients, complete bypass to maintain brain perfusion was performed for an average 17.6±6.9 minutes; intraoperative transcranial Doppler monitoring during flow bypass showed no notable decline in intracranial blood flow velocity. Two patients suffered stroke; one recovered completely. Conclusion: A cerebral protection strategy that integrates internal and external blood flow bypass techniques to maintain adequate brain blood flow is simple and feasible for in situ triple-fenestration aortic arch stent-graft repairs. However, neurological complications were not avoided with this method; thus, further research and development are required.

Summary High‐density genetic map is a valuable tool for exploring novel genomic information, quantitative trait locus (QTL) mapping and gene discovery of economically agronomic traits in plant species. However, high‐resolution genetic map applied to tag QTLs associated with important traits and to investigate genomic features underlying recombination landscape in radish (Raphanus sativus) remains largely unexplored. In this study, an ultra‐high‐density genetic map with 378 738 SNPs covering 1306.8 cM in nine radish linkage groups (LGs) was developed by a whole‐genome sequencing‐based approach. A total of 18 QTLs for 11 horticulture traits were detected. The map‐based cloning data indicated that the R2R3‐MYB transcription factor RsMYB90 was a crucial candidate gene determining the taproot skin colour. Comparative genomics analysis among radish, Brassica rapa and B. oleracea genome revealed several genomic rearrangements existed in the radish genome. The highly uneven distribution of recombination was observed across the nine radish chromosomes. Totally, 504 recombination hot regions (RHRs) were enriched near gene promoters and terminators. The recombination rate in RHRs was positively correlated with the density of SNPs and gene, and GC content, respectively. Functional annotation indicated that genes within RHRs were mainly involved in metabolic process and binding. Three QTLs for three traits were found in the RHRs. The results provide novel insights into the radish genome evolution and recombination landscape, and facilitate the development of effective strategies for molecular breeding by targeting and dissecting important traits in radish.

Objectives The aim of this study was to analyze the short-term outcomes of in situ fenestration and discuss its feasibility and safety for the treatment of aortic dissection or aneurysm involving aortic arch. Methods A retrospective single-center review was conducted on patients who were treated with ISF technique to revascularize supra-arch branches from Jun 2017 to Oct 2019. Computed tomographic angiography (CTA) was performed to assess the patency of bridging stents, endoleaks and prognosis prior to discharge, after 3 months, 6 months, 12 months and yearly thereafter. Patient demographics, operative details, clinical outcomes, and complications were analyzed and then discussed in this paper. Results A total of 21 patients were diagnosed with arch pathologies, 5 type A aortic dissections, 12 type B aortic dissections and 4 thoracic aortic aneurysms. There were 19 men and 2 women (mean age 60.7 ± 15.3). 8 cases were treated with t hree-fenestration stent grafts, 1 case with two-fenestration stent graft, and 12 case with single-fenestration stent grafts. Overall technical success rate was 95.2%. Mean operation time was 227.4 ± 143.8 min. Complications were intraoperative hemorrhage (>1000 ml, 2), stroke (2), hydropericardium (1) and endoleaks (2 type Ⅲ, 1 type Ⅰ). There was no aorta-related mortality or late endoleaks during the mean follow-up of 25.5 ± 6.2 months. All the bridging stents remained patent and there was no migration according to follow-up CTA. Conclusion With low complication and mortality rate, ISF is an effective and feasible method for the total endovascular aortic arch repair. Long-term follow-up study is needed to evaluate its durability.

We detected a QTL qHSW-16 undergone strong selection associated with seed weight and identified a novel candidate gene controlling seed weight candidate gene for this major QTL by qRT-PCT. Soybean [Glycine max (L.) Merr.] provides more than half of the world’s oilseed production. To expand its germplasm resources useful for breeding increased yield and oil quality cultivars, it is necessary to resolve the diversity and evolutionary history of this crop. In this work, we resequenced 283 soybean accessions from China and obtained a large number of high-quality SNPs for investigation of the population genetics that underpin variation in seed weight and other agronomic traits. Selective signature analysis detected 78 (~ 25.0 Mb) and 39 (~ 22.60 Mb) novel putative selective signals that were selected during soybean domestication and improvement, respectively. Genome-wide association study (GWAS) identified five loci associated with seed weight. Among these QTLs, qHSW-16, overlapped with the improvement-selective region on chromosome 16, suggesting that this QTL may be underwent strong selection during soybean improvement. Of the 18 candidate genes in qHSW-16, only SoyZH13_16G122400 showed higher expression levels in a large seed variety compared to a small seed variety during seed development. These results identify SoyZH13_16G122400 as a novel candidate gene controlling seed weight and provide foundational insights into the molecular targets for breeding improvement of seed weight and potential seed yield in soybean.

The CPA (cation proton antiporter) family plays an essential role during plant stress tolerance by regulating ionic and pH homeostasis of the cell. Radish fleshy roots are susceptible to abiotic stress during growth and development, especially salt stress. To date, CPA family genes have not yet been identified in radish and the biological functions remain unclear. In this study, 60 CPA candidate genes in radish were identified on the whole genome level, which were divided into three subfamilies including the Na+/H+ exchanger (NHX), K+ efflux antiporter (KEA), and cation/H+ exchanger (CHX) families. In total, 58 of the 60 RsCPA genes were localized to the nine chromosomes. RNA-seq. data showed that 60 RsCPA genes had various expression levels in the leaves, roots, cortex, cambium, and xylem at different development stages, as well as under different abiotic stresses. RT&ndash, qPCR analysis indicated that all nine RsNHXs genes showed up regulated trends after 250 mM NaCl exposure at 3, 6, 12, and 24h. The RsCPA31 (RsNHX1) gene, which might be the most important members of the RsNHX subfamily, exhibited obvious increased expression levels during 24h salt stress treatment. Heterologous over-and inhibited-expression of RsNHX1 in Arabidopsis showed that RsNHX1 had a positive function in salt tolerance. Furthermore, a turnip yellow mosaic virus (TYMV)-induced gene silence (VIGS) system was firstly used to functionally characterize the candidate gene in radish, which showed that plant with the silence of endogenous RsNHX1 was more susceptible to the salt stress. According to our results we provide insights into the complexity of the RsCPA gene family and a valuable resource to explore the potential functions of RsCPA genes in radish.

The CPA (cation proton antiporter) family plays an essential role during plant stress tolerance by regulating ionic and pH homeostasis of the cell. Radish fleshy roots are susceptible to abiotic stress during growth and development, especially salt stress. To date, CPA family genes have not yet been identified in radish and the biological functions remain unclear. In this study, 60 CPA candidate genes in radish were identified on the whole genome level, which were divided into three subfamilies including the Na+/H+ exchanger (NHX), K+ efflux antiporter (KEA), and cation/H+ exchanger (CHX) families. In total, 58 of the 60 RsCPA genes were localized to the nine chromosomes. RNA-seq. data showed that 60 RsCPA genes had various expression levels in the leaves, roots, cortex, cambium, and xylem at different development stages, as well as under different abiotic stresses. RT–qPCR analysis indicated that all nine RsNHXs genes showed up regulated trends after 250 mM NaCl exposure at 3, 6, 12, and 24h. The RsCPA31 (RsNHX1) gene, which might be the most important members of the RsNHX subfamily, exhibited obvious increased expression levels during 24h salt stress treatment. Heterologous over-and inhibited-expression of RsNHX1 in Arabidopsis showed that RsNHX1 had a positive function in salt tolerance. Furthermore, a turnip yellow mosaic virus (TYMV)-induced gene silence (VIGS) system was firstly used to functionally characterize the candidate gene in radish, which showed that plant with the silence of endogenous RsNHX1 was more susceptible to the salt stress. According to our results we provide insights into the complexity of the RsCPA gene family and a valuable resource to explore the potential functions of RsCPA genes in radish.

Circular RNAs (circRNAs) are a class of noncoding RNAs produced by a noncanonical form of alternative splicing called back-splicing. To investigate a potential role of circRNAs in the p53 pathway, we analyzed RNA sequencing (RNA-seq) data from colorectal cancer cell lines (HCT116, RKO, and SW48) that were untreated or treated with a DNA-damaging agent. Surprisingly, unlike the strong p53-dependent induction of hundreds of p53-induced mRNAs upon DNA damage, only a few circRNAs were upregulated from p53-induced genes. circ-MDM2, an annotated circRNA from the MDM2 locus, was one of the handful of circRNAs that originated from a p53-induced gene. Given the central role of MDM2 in suppressing p53 protein levels and p53 activity, we investigated the function of circ-MDM2 Knocking down circ-MDM2 with small interfering RNAs (siRNAs) that targeted circ-MDM2 did not alter MDM2 mRNA or MDM2 protein levels but resulted in increased basal p53 levels and growth defects in vitro and in vivo Consistent with these results, transcriptome profiling showed increased expression of several direct p53 targets, reduced retinoblastoma protein (Rb) phosphorylation, and defects in G1-S progression upon silencing circ-MDM2 Our results on the initial characterization of circ-MDM2 identify a new player from the MDM2 locus that suppresses p53 levels and cell cycle progression.

Drying is one of the most vital preservation techniques used in the food industry. It demands different levels of energy to produce commercially high-quality-dried food products. Novel dryi...

Tomato chlorosis virus (ToCV), a species of single-stranded RNA virus belonging to the Crinivirus genus, and Tomato yellow leaf curl virus (TYLCV), a species of single-stranded circular DNA virus belonging to the Begomovirus genus, are two major emerging viruses transmitted by whiteflies and are causing huge losses to tomato production worldwide. To facilitate the simultaneous detection of both viruses in co-infected plants for disease control, a duplex reverse-transcription PCR assay was developed. The assay used three primers, a degenerate reverse primer targeting a conserved region of TYLCV and the RNA2 of ToCV, and two virus-specific forward primers targeting the minor coat protein gene of ToCV and the C3 gene of TYLCV, respectively, to amplify a 762-bp and a 338-bp fragment from ToCV and TYLCV, respectively, in a single reaction. The concentration of the primers, annealing temperature and amplification cycles used in the assay were optimized, and the sensitivity of the assay was assessed. Using this assay, 150 tomato leaf samples collected from the field during 2018 were tested. The results showed that both viruses could be detected simultaneously in co-infected field samples. The assay should benefit the rapid detection of these two viruses in tomato crops and would facilitate early warning of infections for the control of the two virus diseases.

To report the early results of castor device, a kind of unibody single-branched stent graft, in the treatment of type B aortic dissection (TBAD) involving the LSA. From April 2013 to February 2014, 21 patients with TBADs underwent TEVAR with LSA revascularization by unibody single-branched stent grafts. Three patients with penetrating aortic ulcers in the aortic arch received additional reconstruction of left common carotid artery with chimney technique. Follow-up evaluations were conducted with computed tomography angiography (CTA) at 6, 12 months and annually after that. All of the proximal entry tears were completely excluded. Good patency of the grafts was found in all cases. A small type I endoleak occurred in one patient during the procedure. Perioperative mortality is null, and there was no occurrence of serious complications. All patients completed the follow-up except one lost contact after discharge. One death occurred within 6 months after the operation, resulting from myocardial infarction, considered unrelated to the stent implantation. No endoleak occurred during follow-up. One compression of a chimney stent and one twist of side branch graft of castor were observed in 2 different patients, respectively. In other cases, CTA scans showed good patency of both the branched and chimney grafts. Two patients had partial thrombosis of the false lumen during follow-up. In other patients, complete thrombosis in the false lumen in thoracic aorta was revealed. The single-branched stent graft was safe and efficient in the 1-year follow-up. Further studies are required to determine its long-term outcomes.

Basal p53 levels are tightly suppressed under normal conditions. Disrupting this regulation results in elevated p53 levels to induce cell cycle arrest, apoptosis, and tumor suppression. Here, we report the suppression of basal p53 levels by a nuclear, p53-regulated long noncoding RNA that we termed PURPL (p53 upregulated regulator of p53 levels). Targeted depletion of PURPL in colorectal cancer cells results in elevated basal p53 levels and induces growth defects in cell culture and in mouse xenografts. PURPL associates with MYBBP1A, a protein that binds to and stabilizes p53, and inhibits the formation of the p53-MYBBP1A complex. In the absence of PURPL, MYBBP1A interacts with and stabilizes p53. Silencing MYBBP1A significantly rescues basal p53 levels and proliferation in PURPL-deficient cells, suggesting that MYBBP1A mediates the effect of PURPL in regulating p53. These results reveal a p53-PURPL auto-regulatory feedback loop and demonstrate a role for PURPL in maintaining basal p53 levels.

Background Activation of the YAP (Yes‐associated protein) pathway has been demonstrated to be related to smooth muscle cells ( SMC s) phenotypic modulation and vessel restenosis. The aim of this study was to illustrate the molecular mechanisms that regulate the expression of YAP during the process of SMC s phenotypic switch. Whether the molecular basis identified in the study could be a potential therapeutic target for drug‐eluting stents is further tested. Methods and Results In cell culture and in rat carotid arterial injury models, Sp‐1 (specificity protein 1) expression was significantly induced, and correlated with SMC s proliferative phenotype. Overexpression of Sp‐1 promoted SMC s proliferation and migration. Conversely, siSp‐1 transfection or Sp‐1 inhibitor Mithramycin A treatment attenuates SMC proliferation and migration. Through gain‐ and loss‐function assays, we demonstrated that YAP was involved in Sp‐1‐mediated SMC phenotypic switch. Mechanistically, activated Sp‐1 regulated YAP transcriptional expression through binding to its promoter. Moreover, we fabricated a Sp‐1 inhibitor Mithramycin A‐eluting stent and further tested it. In the rabbit carotid model, Mithramycin A‐eluting stent inhibited YAP transcription and attenuated in‐stent restenosis through regulating YAP ‐mediated SMC phenotypic switch. Conclusions Sp‐1 controls phenotypic modulation of SMC by regulating transcription factor YAP . Drug‐eluting stent targeting Sp‐1 might represent a novel therapeutic strategy to prevent in‐stent restenosis.

Circular RNAs (circRNAs) are a class of noncoding RNAs produced by a noncanonical form of alternative splicing called back-splicing. To investigate a potential role of circRNAs in the p53 pathway, we analyzed RNA sequencing (RNA-seq) data from colorectal cancer cell lines (HCT116, RKO, and SW48) that were untreated or treated with a DNA-damaging agent. Surprisingly, unlike the strong p53-dependent induction of hundreds of p53-induced mRNAs upon DNA damage, only a few circRNAs were upregulated from p53-induced genes. circ-MDM2, an annotated circRNA from the MDM2 locus, was one of the handful of circRNAs that originated from a p53-induced gene. Given the central role of MDM2 in suppressing p53 protein levels and p53 activity, we investigated the function of circ-MDM2. Knocking down circ-MDM2 with small interfering RNAs (siRNAs) that targeted circ-MDM2 did not alter MDM2 mRNA or MDM2 protein levels but resulted in increased basal p53 levels and growth defects in vitro and in vivo. Consistent with these results, transcriptome profiling showed increased expression of several direct p53 targets, reduced retinoblastoma protein (Rb) phosphorylation, and defects in G(1)-S progression upon silencing circ-MDM2. Our results on the initial characterization of circ-MDM2 identify a new player from the MDM2 locus that suppresses p53 levels and cell cycle progression.

Background Anthocyanin synthesis is affected by many factors, among which temperature is an important environmental factor. Eggplant is usually exposed to high temperatures during the cultivation season in Shanghai, China. Therefore,RNA -seq analysis was used to determine the effects of high-temperature stress on gene expression in the anthocyanin biosynthetic pathway of eggplant (Solanum melongena L.). Results We tested the heat-resistant cultivar ‘Tewangda’. The plants were incubated at 38 °C and 45 °C, and the suitable temperature for eggplant growth was used as a control. The treatment times were 3 h and 6 h. The skin of the eggplant was taken for transcriptome sequencing, qRT-PCR assays and bioinformatic analysis. The results showed that 770 genes were differentially expressed between different treatments. Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analyses identified 16 genes related to anthocyanin biosynthesis, among which CHSB was upregulated. Other genes, including BHLH62, MYB380, CHI3, CHI, CCOAOMT, AN3, ACT-2, HST, 5MA-T1, CYP75A2, ANT17, RT, PAL2, and anthocyanin 5-aromatic acyltransferase were downregulated. In addition, the Myb family transcription factor PHL11 was upregulated in the CK 3 h vs 45 °C 3 h, CK 3 h vs 38 °C 3 h, and CK 6 h vs 38 °C 6 h comparisons, and the transcription factor bHLH35 was upregulated in the CK 3 h vs 38 °C 3 h and CK 6 h vs 38 °C 6 h comparisons. Conclusion These results indicated that high temperature will downregulate most of the genes in the anthocyanin biosynthetic pathway of eggplant. Our data have a reference value for the heat resistance mechanism of eggplant and can provide directions for molecular breeding of heat-resistant germplasm with anthocyanin content in eggplant. Electronic supplementary material The online version of this article (10.1186/s12870-019-1960-2) contains supplementary material, which is available to authorized users.

Bruchids (Callosobruchus spp.) are destructive storage pests of mung beans (Vigna radiata). Bruchids infest mature seeds during storage and in the field causing heavy losses. Bruchid resistance in mung bean has been characterized as a dominant trait controlled by a single gene. Several independent mapping studies showed that the Br locus on chromosome 5 was a key quantitative trait loci (QTL) involved in bruchid resistance. Two polygalacturonase-inhibitor protein (PGIP) family genes, VrPGIP1 and VrPGIP2, located in the Br locus may be the primary genes responsible for bruchid resistance in mung bean but no experimental proof is available. We isolated the VrPGIP1 and VrPGIP2 genes from bruchid resistant mung bean cultivar V2802 and purified the proteins by prokaryotic expression. Both VrPGIP1 and VrPGIP2 had polygalacturonase inhibitor activity and both of the PGIP proteins conferred resistance to bruchids in an artificial seed test system. VrPGIPs can inhibit the enzyme activity of polygalacturonase present in males, females and fourth instar larvae of C. maculatus. These results demonstrated that VrPGIP1 and VrPGIP2 play a critical role in bruchid resistance probably through inhibiting polygalacturonase activity.

Table S1. Comparison results with reference genome comparison rates. A:Comparison results with reference genome comparison rates. Total reads: the number of statistics of the sequencing sequence after sequencing data filtering (Clean reads); Total mapped: the number of sequencing sequences that can be mapped to the genome; in general, if there is no pollution And the percentage of the data is greater than 70% when the reference genome is selected appropriately; Multiple mapped: the number of sequencing sequences with multiple alignment positions on the reference sequence;Uniquely mapped: in the reference sequence The number of sequencing sequences with unique alignment positions;Read-1, Read-2: the number of left reads and right reads mapped to the reference genome respectively. B:Comparison results with reference genome comparison rates. Reads map to ‘+’, Reads map to ‘-’:Statistics of sequences mapped to the positive and negative strands on the genome;Splice reads: Total mapped reads, segmentally aligned to the sequencing sequences on the two exons (also The statistics called Junction reads, Non-splice reads the statistics of the sequence to be sequenced to the exon. The percentage of splice reads depends on the length of the sequence;Reads mapped in proper pairs: double-ended ratio. (DOCX 14 kb)