Tissue culture and Agrobacterium-mediated genetic transformation of the oil crop sunflower.

Sunflower is one of the four major oil crops in the world. 'Zaoaidatou' (ZADT), the main variety of oil sunflower in the northwest of China, has a short growth cycle, high yield, and high resistance to abiotic stress. However, the ability to tolerate adervesity is limited. Therefore, in this study, we used the retention line of backbone parent ZADT as material to establish its tissue culture and genetic transformation system for new variety cultivating to enhance resistance and yields by molecular breeding. The combination of 0.05 mg/L IAA and 2 mg/L KT in MS was more suitable for direct induction of adventitious buds with cotyledon nodes and the addition of 0.9 mg/L IBA to MS was for adventitious rooting. On this basis, an efficient Agrobacterium tumefaciens-mediated genetic transformation system for ZADT was developed by the screening of kanamycin and optimization of transformation conditions. The rate of positive seedlings reached 8.0%, as determined by polymerase chain reaction (PCR), under the condition of 45 mg/L kanamycin, bacterial density of OD600 0.8, infection time of 30 min, and co-cultivation of three days. These efficient regeneration and genetic transformation platforms are very useful for accelerating the molecular breeding process on sunflower.

The biological behavior and clinical outcome of pituitary adenoma are affected by the microenvironment.

BACKGROUND: Pituitary adenoma is one of the most common brain tumors. Most pituitary adenomas are benign and can be cured by surgery and/or medication. However, some pituitary adenomas show aggressive growth with a fast growth rate and are resistant to conventional treatments such as surgery, drug therapy, and radiation therapy. These tumors, referred to as refractory pituitary adenomas, often relapse or regrow in the early postoperative period. The tumor microenvironment (TME) has recently been identified as an important factor affecting the biological manifestations of tumors and acts as the main battlefield between the tumor and the host immune system. MAIN BODY: In this review, we focus on describing TME in pituitary adenomas and refractory pituitary adenomas. Research on the immune microenvironment of pituitary adenomas is currently focused on immune cells such as macrophages and lymphocytes, and extensive research and experimental verifications are still required regarding other components of the TME. In particular, studies are needed to determine the role of the TME in the specific biological behaviors of refractory pituitary adenomas, such as high invasion, fast recurrence rate, and high tolerance to traditional treatments and to identify the mechanisms involved. CONCLUSION: Overall, we summarize the similarities and differences between the TME of pituitary adenomas and refractory pituitary adenomas as well as the changes in the biological behavior of pituitary adenomas that may be caused by the microenvironment. These changes greatly affect the outcome of patients.

Polymorphism rs2327430 in TCF21 predicts the risk and prognosis of gastric cancer by affecting the binding between TFAP2A and TCF21.

BACKGROUND: Single nuclear polymorphisms (SNPs) have been published to be correlated with multiple diseases. Transcription Factor 21 (TCF21) is a critical transcription factor involved in various types of cancers. However, the association of TCF21 genetic polymorphisms with gastric cancer (GC) susceptibility and prognosis remains unclear. METHODS: A case-control study comprising 890 patients diagnosed with GC and an equal number of cancer-free controls was conducted. After rigorous statistical analysis, molecular experiments were carried out to elucidate the functional significance of the SNPs in the context of GC. RESULTS: TCF21 rs2327430 (OR = 0.78, P = 0.026) provides protection against GC, while rs4896011 (OR = 1.39, P = 0.005) exhibit significant associations with GC risk. Furthermore, patients with the (TC + CC) genotype of rs2327430 demonstrate a relatively favorable prognosis (OR = 0.47, P = 0.012). Mechanistically, chromatin immunoprecipitation assay and luciferase reporter assay revealed that the C allele of rs2327430 disrupts the binding of Transcription Factor AP-2 Alpha (TFAP2A) to the promoter region of TCF21, resulting in increased expression of TCF21 and inhibition of malignant behaviors in GC cells. CONCLUSION: Our findings highlight the significant role of TCF21 SNPs in both the risk and prognosis of GC and provide valuable insights into the underlying molecular mechanisms. Specifically, the disruptive effect of rs2327430 on TCF21 expression and its ability to modulate malignant cell behaviors suggest that rs2327430 may serve as a potential predictive marker for GC risk and prognosis.

PESSA: A web tool for pathway enrichment score-based survival analysis in cancer.

The activation levels of biologically significant gene sets are emerging tumor molecular markers and play an irreplaceable role in the tumor research field; however, web-based tools for prognostic analyses using it as a tumor molecular marker remain scarce. We developed a web-based tool PESSA for survival analysis using gene set activation levels. All data analyses were implemented via R. Activation levels of The Molecular Signatures Database (MSigDB) gene sets were assessed using the single sample gene set enrichment analysis (ssGSEA) method based on data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), The European Genome-phenome Archive (EGA) and supplementary tables of articles. PESSA was used to perform median and optimal cut-off dichotomous grouping of ssGSEA scores for each dataset, relying on the survival and survminer packages for survival analysis and visualisation. PESSA is an open-access web tool for visualizing the results of tumor prognostic analyses using gene set activation levels. A total of 238 datasets from the GEO, TCGA, EGA, and supplementary tables of articles; covering 51 cancer types and 13 survival outcome types; and 13,434 tumor-related gene sets are obtained from MSigDB for pre-grouping. Users can obtain the results, including Kaplan-Meier analyses based on the median and optimal cut-off values and accompanying visualization plots and the Cox regression analyses of dichotomous and continuous variables, by selecting the gene set markers of interest. PESSA (https://smuonco.shinyapps.io/PESSA/ OR http://robinl-lab.com/PESSA) is a large-scale web-based tumor survival analysis tool covering a large amount of data that creatively uses predefined gene set activation levels as molecular markers of tumors.

Integrated Exploration of Epigenetic Dysregulation Reveals a Stemness/EMT Subtype and MMP12 Linked to the Progression and Prognosis in Hepatocellular Carcinoma.

Epigenetic dysregulation drives aberrant transcriptional programs playing a critical role in hepatocellular carcinoma (HCC), which may provide novel insights into the heterogeneity of HCC. This study performed an integrated exploration on the epigenetic dysregulation of miRNA and methylation. We discovered and validated three patterns endowed with gene-related transcriptional traits and clinical outcomes. Specially, a stemness/epithelial-mesenchymal transition (EMT) subtype was featured by immune exhaustion and the worst prognosis. Besides, MMP12, a characteristic gene, was highly expressed in the stemness/EMT subtype, which was verified as a pivotal regulator linked to the unfavorable prognosis and further proven to promote tumor proliferation, invasion, and metastasis in vitro experiments. Proteomic analysis by mass spectrometry sequencing also indicated that the overexpression of MMP12 was significantly associated with cell proliferation and adhesion. Taken together, this study unveils innovative insights into epigenetic dysregulation and identifies a stemness/EMT subtype-specific gene, MMP12, correlated with the progression and prognosis of HCC.

Development and validation of a radiosensitivity model to evaluate radiotherapy benefits in pan-cancer.

Radiotherapy, one of the most fundamental cancer treatments, is confronted with the dilemma of treatment failure due to radioresistance. To predict the radiosensitivity and improve tumor treatment efficiency in pan-cancer, we developed a model called Radiation Intrinsic Sensitivity Evaluation (RISE). The RISE model was built using cell line-based mRNA sequencing data from five tumor types with varying radiation sensitivity. Through four cell-derived datasets, two public tissue-derived cohorts, and one local cohort of 42 nasopharyngeal carcinoma patients, we demonstrated that RISE could effectively predict the level of radiation sensitivity (area under the ROC curve [AUC] from 0.666 to 1 across different datasets). After the verification by the colony formation assay and flow cytometric analysis of apoptosis, our four well-established radioresistant cell models successfully proved higher RISE values in radioresistant cells by RT-qPCR experiments. We also explored the prognostic value of RISE in five independent TCGA cohorts consisting of 1137 patients who received radiation therapy and found that RISE was an independent adverse prognostic factor (pooled multivariate Cox regression hazard ratio [HR]: 1.84, 95% CI 1.39-2.42; p < 0.01). RISE showed a promising ability to evaluate the radiotherapy benefit while predicting the prognosis of cancer patients, enabling clinicians to make individualized radiotherapy strategies in the future and improve the success rate of radiotherapy.

Burden of Stroke Attributable to Nonoptimal Temperature in 204 Countries and Territories: A Population-Based Study, 1990-2019.

BACKGROUND AND OBJECTIVES: Stroke attributable to nonoptimal temperature needs more attention with dramatic climate change. The aim of this study was to estimate the global burden and distribution characteristics of the burden. METHODS: In this ecological study, we collected data from the Climate Research Unit Gridded Time Series, the World Bank databases, and the Global Burden of Diseases study to estimate the distribution of burden. We used the joinpoint model, decomposition analysis, age-period-cohort model, panel data analysis, and health inequality analysis to assess the different types of stroke burden attributable to different climatic conditions. RESULTS: The burden of stroke attributable to nonoptimal temperature continued to grow, and aging was a key factor in this increase. In 2019, 521,031 (95% uncertainty interval [UI] 402,433-663,996) deaths and 9,423,649 (95% UI 7,207,660-12,055,172) disability-adjusted life years [DALYs] attributable to stroke due to nonoptimal temperature were recorded globally. Globally, men (age-standardized mortality rate [ASMR] 7.70, 95% UI 5.80-9.73; age-standardized DALY rate [ASDR] 139.69, 95% UI 102.96-178.54 in 2019) had a heavier burden than women (ASMR 5.89, 95% UI 4.50-7.60; ASDR 96.02, 95% UI 72.62-123.85 in 2019). Central Asia (ASMR 18.12, 95% UI 13.40-24.53; ASDR 327.35, 95% UI 240.24-440.61 in 2019) had the heaviest burden at the regional level. In the national level, North Macedonia (ASMR 32.97, 95% UI 20.57-47.44 in 2019) and Mongolia (ASDR 568.54, 95% UI 242.03-1,031.14 in 2019) had the highest ASMR/ASDR, respectively. Low temperature currently contributes to the main burden (deaths 474,002, 95% UI 355,077-606,537; DALYs 8,357,198, 95% UI 6,186,217-10,801,911 attributable to low temperature vs deaths 48,030, 95% UI 5,630-104,370; DALYs 1,089,329, 95% UI 112,690-2,375,345 attributable to high temperature in 2019). However, the burden due to high temperature has increased rapidly, especially among people aged older than 10 years, and was disproportionately concentrated in low sociodemographic index (SDI) regions such as Africa. In addition, the rapid increase in the stroke burden due to high temperature in Central Asia also requires special attention. DISCUSSION: This is the first study to assess the global stroke burden attributed to nonoptimal temperature. The dramatic increase in the burden due to high temperature requires special attention, especially in low-SDI countries.

Large-scale genome-wide association studies reveal the genetic causal etiology between air pollutants and autoimmune diseases.

BACKGROUND: Epidemiological evidence links a close correlation between long-term exposure to air pollutants and autoimmune diseases, while the causality remained unknown. METHODS: Two-sample Mendelian randomization (TSMR) was used to investigate the role of PM10, PM2.5, NO2, and NOX (N = 423,796-456,380) in 15 autoimmune diseases (N = 14,890-314,995) using data from large European GWASs including UKB, FINNGEN, IMSGC, and IPSCSG. Multivariable Mendelian randomization (MVMR) was conducted to investigate the direct effect of each air pollutant and the mediating role of common factors, including body mass index (BMI), alcohol consumption, smoking status, and household income. Transcriptome-wide association studies (TWAS), two-step MR, and colocalization analyses were performed to explore underlying mechanisms between air pollution and autoimmune diseases. RESULTS: In TSMR, after correction of multiple testing, hypothyroidism was causally associated with higher exposure to NO2 [odds ratio (OR): 1.37, p = 9.08 × 10-4] and NOX [OR: 1.34, p = 2.86 × 10-3], ulcerative colitis (UC) was causally associated with higher exposure to NOX [OR: 2.24, p = 1.23 × 10-2] and PM2.5 [OR: 2.60, p = 5.96 × 10-3], rheumatoid arthritis was causally associated with higher exposure to NOX [OR: 1.72, p = 1.50 × 10-2], systemic lupus erythematosus was causally associated with higher exposure to NOX [OR: 4.92, p = 6.89 × 10-3], celiac disease was causally associated with lower exposure to NOX [OR: 0.14, p = 6.74 × 10-4] and PM2.5 [OR: 0.17, p = 3.18 × 10-3]. The risky effects of PM2.5 on UC remained significant in MVMR analyses after adjusting for other air pollutants. MVMR revealed several common mediators between air pollutants and autoimmune diseases. Transcriptional analysis identified specific gene transcripts and pathways interconnecting air pollutants and autoimmune diseases. Two-step MR revealed that POR, HSPA1B, and BRD2 might mediate from air pollutants to autoimmune diseases. POR pQTL (rs59882870, PPH4=1.00) strongly colocalized with autoimmune diseases. CONCLUSION: This research underscores the necessity of rigorous air pollutant surveillance within public health studies to curb the prevalence of autoimmune diseases.

Role of body mass index and weight change in the risk of cancer: A systematic review and meta-analysis of 66 cohort studies.

Background: This study was designed to evaluate the effects of body mass index (BMI) and weight change on the risk of developing cancer overall and cancer at different sites. Methods: We searched PubMed and other databases up to July 2023 using the keywords related to 'risk', 'cancer', 'weight', 'overweight', and 'obesity'. We identified eligible studies, and the inclusion criteria encompassed cohort studies in English that focused on cancer diagnosis and included BMI or weight change as an exposure factor. Multiple authors performed data extraction and quality assessment, and statistical analyses were carried out using RevMan and R software. We used random- or fixed-effects models to calculate the pooled relative risk (RR) or hazard ratio along with 95% confidence intervals (CIs). We used the Newcastle-Ottawa Scale to assess study quality. Results: Analysis included 66 cohort studies. Compared to underweight or normal weight, overweight or obesity was associated with an increased risk of endometrial cancer, kidney cancer, and liver cancer but a decreased risk of prostate cancer and lung cancer. Being underweight was associated with an increased risk of gastric cancer and lung cancer but not that of postmenopausal breast cancer or female reproductive cancer. In addition, weight loss of more than five kg was protective against overall cancer risk. Conclusions: Overweight and obesity increase the risk of most cancers, and weight loss of >5 kg reduces overall cancer risk. These findings provide insights for cancer prevention and help to elucidate the mechanisms underlying cancer development. Registration: Reviewregistry1786.

Combining bulk and scRNA-seq to explore the molecular mechanisms governing the distinct efferocytosis activities of a macrophage subpopulation in PDAC.

Pancreatic ductal adenocarcinoma (PDAC), a very aggressive tumour, is currently the third leading cause of cancer-related deaths. Unfortunately, many patients face the issue of inoperability at the diagnostic phase leading to a quite dismal prognosis. The onset of metastatic processes has a crucial role in the elevated mortality rates linked to PDAC. Individuals with metastatic advances receive only palliative therapy and have a grim prognosis. It is essential to carefully analyse the intricacies of the metastatic process to enhance the prognosis for individuals with PDAC. Malignancy development is greatly impacted by the process of macrophage efferocytosis. Our current knowledge about the complete range of macrophage efferocytosis activities in PDAC and their intricate interactions with tumour cells is still restricted. This work aims to resolve communication gaps and pinpoint the essential transcription factor that is vital in the immunological response of macrophage populations. We analysed eight PDAC tissue samples sourced from the gene expression omnibus. We utilized several software packages such as Seurat, DoubletFinder, Harmony, Pi, GSVA, CellChat and Monocle from R software together with pySCENIC from Python, to analyse the single-cell RNA sequencing (scRNA-seq) data collected from the PDAC samples. This study involved the analysis of a comprehensive sample of 22,124 cells, which were classified into distinct cell types. These cell types encompassed endothelial and epithelial cells, PDAC cells, as well as various immune cells, including CD4+ T cells, CD8+ T cells, NK cells, B cells, plasma cells, mast cells, monocytes, DC cells and different subtypes of macrophages, namely C0 macrophage TGM2+, C1 macrophage PFN1+, C2 macrophage GAS6+ and C3 macrophage APOC3+. The differentiation between tumour cells and epithelial cells was achieved by the implementation of CopyKat analysis, resulting in the detection and categorization of 1941 PDAC cells. The amplification/deletion patterns observed in PDAC cells on many chromosomes differ significantly from those observed in epithelial cells. The study of Pseudotime Trajectories demonstrated that the C0 macrophage subtype expressing TGM2+ had the lowest level of differentiation. Additionally, the examination of gene set scores related to efferocytosis suggested that this subtype displayed higher activity during the efferocytosis process compared to other subtypes. The most active transcription factors for each macrophage subtype were identified as BACH1, NFE2, TEAD4 and ARID3A. In conclusion, the examination of human PDAC tissue samples using immunofluorescence analysis demonstrated the co-localization of CD68 and CD11b within regions exhibiting the presence of keratin (KRT) and alpha-smooth muscle actin (α-SMA). This observation implies a spatial association between macrophages, fibroblasts, and epithelial cells. There is variation in the expression of efferocytosis-associated genes between C0 macrophage TGM2+ and other macrophage cell types. This observation implies that the diversity of macrophage cells might potentially influence the metastatic advancement of PDAC. Moreover, the central transcription factor of different macrophage subtypes offers a promising opportunity for targeted immunotherapy in the treatment of PDAC.

Potential anti-tumor effects of regulatory T cells in the tumor microenvironment: a review.

Regulatory T cells (Tregs) expressing the transcription factor FoxP3 are essential for maintaining immunological balance and are a significant component of the immunosuppressive tumor microenvironment (TME). Single-cell RNA sequencing (ScRNA-seq) technology has shown that Tregs exhibit significant plasticity and functional diversity in various tumors within the TME. This results in Tregs playing a dual role in the TME, which is not always centered around supporting tumor progression as typically believed. Abundant data confirms the anti-tumor activities of Tregs and their correlation with enhanced patient prognosis in specific types of malignancies. In this review, we summarize the potential anti-tumor actions of Tregs, including suppressing tumor-promoting inflammatory responses and boosting anti-tumor immunity. In addition, this study outlines the spatial and temporal variations in Tregs function to emphasize that their predictive significance in malignancies may change. It is essential to comprehend the functional diversity and potential anti-tumor effects of Tregs to improve tumor therapy strategies.

Correction: In situ formation of J-aggregate in the tumor microenvironment using acidity responsive polypeptide nanoparticle encapsulating galactose-conjugated BODIPY dye for NIR-II phototheranostics.

Correction for 'In situ formation of J-aggregate in the tumor microenvironment using acidity responsive polypeptide nanoparticle encapsulating galactose-conjugated BODIPY dye for NIR-II phototheranostics' by Huiping Dang et al., J. Mater. Chem. B, 2022, 10, 5279-5290, https://doi.org/10.1039/D2TB00705C.

CTLs heterogeneity and plasticity: implications for cancer immunotherapy.

Cytotoxic T lymphocytes (CTLs) play critical antitumor roles, encompassing diverse subsets including CD4+, NK, and γδ T cells beyond conventional CD8+ CTLs. However, definitive CTLs biomarkers remain elusive, as cytotoxicity-molecule expression does not necessarily confer cytotoxic capacity. CTLs differentiation involves transcriptional regulation by factors such as T-bet and Blimp-1, although epigenetic regulation of CTLs is less clear. CTLs promote tumor killing through cytotoxic granules and death receptor pathways, but may also stimulate tumorigenesis in some contexts. Given that CTLs cytotoxicity varies across tumors, enhancing this function is critical. This review summarizes current knowledge on CTLs subsets, biomarkers, differentiation mechanisms, cancer-related functions, and strategies for improving cytotoxicity. Key outstanding questions include refining the CTLs definition, characterizing subtype diversity, elucidating differentiation and senescence pathways, delineating CTL-microbe relationships, and enabling multi-omics profiling. A more comprehensive understanding of CTLs biology will facilitate optimization of their immunotherapy applications. Overall, this review synthesizes the heterogeneity, regulation, functional roles, and enhancement strategies of CTLs in antitumor immunity, highlighting gaps in our knowledge of subtype diversity, definitive biomarkers, epigenetic control, microbial interactions, and multi-omics characterization. Addressing these questions will refine our understanding of CTLs immunology to better leverage cytotoxic functions against cancer.

Cancer associated fibroblasts-derived SULF1 promotes gastric cancer metastasis and CDDP resistance through the TGFBR3-mediated TGF-ß signaling pathway.

SULF1 has been implicated in a number of malignancies. The function of SULF1 in gastric cancer is disputed. The objective of this study was to examine the role and underlying molecular mechanisms of SULF1 in the context of gastric cancer. We found that the expression of SULF1 was increased in gastric cancer, especially in cancer-associated fibroblasts. The overexpression of SULF1 was found to be significantly correlated with unfavorable prognosis among individuals diagnosed with gastric cancer. Functionally, cancer-associated fibroblasts-derived SULF1 served as a oncogenic molecule which facilitated gastric cancer cells metastasis and CDDP resistance. Mechanistically, SULF1 regulated the communication between gastric cancer cells and cancer-associated fibroblasts in tumor microenvironment as a signaling molecule. Cancer-associated fibroblasts-secreted SULF1 interfered with the interaction between TGF-ß1 and TGFBR3 by combining with TGFBR3 on gastric cancer cell membrane, subsequently activated TGF-ß signaling pathway. In conclusion, our findings have presented novel approaches for potential treatment and prognosis prediction in individuals diagnosed with gastric cancer through the targeting of the CAFs-SULF1-TGFBR3-TGF-ß1 signaling axis.

Unveiling the oncogenic role of CLDN11-secreting fibroblasts in gastric cancer peritoneal metastasis through single-cell sequencing and experimental approaches.

BACKGROUND: Fibroblasts are necessary to the progression of cancer. However, the role of fibroblasts in peritoneal metastasis (PM) of gastric cancer (GC) remains elusive. In this study, we would explore the role of fibroblasts mediated cell interaction in PM of GC. METHODS: Single-cell sequencing data from public database GSE183904 was used to explore the specific fibroblast cluster. Fibroblasts were extracted from PM and GC tissues. The expression level of CXCR7 was verified by western blot, immunohistochemistry. The role of CLDN11 was investigate through in vitro and in vivo study. Multiple immunohistochemistry was used to characterize the tumor microenvironment. RESULTS: CXCR7-positive fibroblasts were significantly enriched in PM of GC. CXCR7 could promote the expression of CLDN11 through activation of the AKT pathway in fibroblasts. Fibroblasts promote the GC proliferation and peritoneal metastasis by secreting CLDN11 in vitro and in vivo. Furthermore, it was revealed that CXCR7-positive fibroblasts were significantly associated with M2-type macrophages infiltration in tissues. CONCLUSION: CXCR7-positive fibroblasts play an essential role in PM of GC via CLDN11. Therapy targeting CXCR7-positive fibroblasts or CLDN11 may be helpful in the treatment of GC with PM.

N6-methyladenosine-modified MIB1 promotes stemness properties and peritoneal metastasis of gastric cancer cells by ubiquitinating DDX3X.

BACKGROUND: Peritoneal metastasis (PM), one of the most typical forms of metastasis in advanced gastric cancer (GC), indicates a poor prognosis. Exploring the potential molecular mechanism of PM is urgently necessary, as it has not been well studied. E3 ubiquitin ligase has been widely established to exert a biological function in various cancers, but its mechanism of action in GC with PM remains unknown. METHODS: The effect of MIB1 on PM of GC was confirmed in vitro and in vivo. Co-immunoprecipitation (Co-IP) and mass spectrometry demonstrated the association between MIB1 and DDX3X. Western blot, flow cytometry and immunofluorescence determined that DDX3X was ubiquitylated by MIB1 and promoted stemness. We further confirmed that METTL3 promoted the up-regulation of MIB1 by RNA immunoprecipitation (RIP), luciferase reporter assay and other experiments. RESULTS: We observed that the E3 ubiquitin ligase Mind bomb 1 (MIB1) was highly expressed in PMs, and patients with PM with high MIB1 expression showed a worse prognosis than those with low MIB1 expression. Mechanistically, our study demonstrated that the E3 ubiquitin ligase MIB1 promoted epithelial-mesenchymal transition (EMT) progression and stemness in GC cells by degrading DDX3X. In addition, METTL3 mediated m6A modification to stabilize MIB1, which required the m6A reader IGF2BP2. CONCLUSIONS: Our study elucidated the specific molecular mechanism by which MIB1 promotes PM of GC, and suggested that targeting the METTL3-MIB1-DDX3X axis may be a promising therapeutic strategy for GC with PM.

Transcription factor PbNAC71 regulates xylem and vessel development to control plant height.

Dwarfism is an important agronomic trait in fruit breeding programs. However, the germplasm resources required to generate dwarf pear (Pyrus spp.) varieties are limited. Moreover, the mechanisms underlying dwarfism remain unclear. In this study, "Yunnan" quince (Cydonia oblonga Mill.) had a dwarfing effect on "Zaosu" pear. Additionally, the dwarfism-related NAC transcription factor gene PbNAC71 was isolated from pear trees comprising "Zaosu" (scion) grafted onto "Yunnan" quince (rootstock). Transgenic Nicotiana benthamiana and pear OHF-333 (Pyrus communis) plants overexpressing PbNAC71 exhibited dwarfism, with a substantially smaller xylem and vessel area relative to the wild-type controls. Yeast one-hybrid, dual-luciferase, chromatin immunoprecipitation-qPCR, and electrophoretic mobility shift assays indicated that PbNAC71 downregulates PbWalls are thin 1 expression by binding to NAC-binding elements in its promoter. Yeast two-hybrid assays showed that PbNAC71 interacts with the E3 ubiquitin ligase PbRING finger protein 217 (PbRNF217). Furthermore, PbRNF217 promotes the ubiquitin-mediated degradation of PbNAC71 by the 26S proteasome, thereby regulating plant height as well as xylem and vessel development. Our findings reveal a mechanism underlying pear dwarfism and expand our understanding of the molecular basis of dwarfism in woody plants.

[Retracted] MicroRNA­203 inhibits the proliferation and invasion of U251 glioblastoma cells by directly targeting PLD2.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the PLD2 western blotting data shown in Fig. 3A and the Transwell invasion assay data shown in Fig. 6 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Molecular Medicine Reports, or were under consideration for publication at around the same time. In view of the fact that certain of these data had already apparently been published previously, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 9: 503­508, 2014; 10.3892/mmr.2013.1814].