Vasorin promotes endothelial differentiation of glioma stem cells via stimulating the transcription of VEGFR2.

Gliomas are highly vascularized malignancies, but current anti-angiogenic treatments have not demonstrated practical improvements in patient survival. Studies have suggested that glioma-derived endothelial cell (GdEC) formed by glioma stem cell (GSC) differentiation may contribute to the failure of this treatment. However, the molecular mechanisms involved in GSC endothelial differentiation remain poorly understood. We previously reported that vasorin (VASN) is highly expressed in glioma and promotes angiogenesis. Here, we show that VASN expression positively correlates with GdEC signatures in glioma patients. VASN promotes the endothelial differentiation capacity of GSC in vitro and participates in the formation of GSC-derived vessels in vivo. Mechanistically, vascular endothelial growth factor receptor 2 (VEGFR2) is a critical factor that mediates the regulation of VASN on GSC endothelial differentiation. Separation of cell chromatin fractionation and chromatin immunoprecipitation-sequencing analysis show that VASN interacts with Notch1 and co-translocates into the cell nuclei, where VASN binds to the VEGFR2 gene promoter to stimulate its transcription during the progression of GSC differentiation into GdEC. Together, these findings elucidate the role and mechanisms of VASN in promoting the endothelial differentiation of GSC and suggest VASN as a potential target for anti-angiogenic therapy based on intervention in GdEC formation in gliomas.

The chromatin remodeller MdRAD5B enhances drought tolerance by coupling MdLHP1-mediated H3K27me3 in apple.

RAD5B belongs to the Rad5/16-like group of the SNF2 family, which often functions in chromatin remodelling. However, whether RAD5B is involved in chromatin remodelling, histone modification, and drought stress tolerance is largely unclear. We identified a drought-inducible chromatin remodeler, MdRAD5B, which positively regulates apple drought tolerance. Transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) analysis showed that MdRAD5B affects the expression of 466 drought-responsive genes through its chromatin remodelling function in response to drought stress. In addition, MdRAD5B interacts with and degrades MdLHP1, a crucial regulator of histone H3 trimethylation at K27 (H3K27me3), through the ubiquitin-independent 20S proteasome. Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis revealed that MdRAD5B modulates the H3K27me3 deposition of 615 genes in response to drought stress. Genetic interaction analysis showed that MdRAD5B mediates the H3K27me3 deposition of drought-responsive genes through MdLHP1, which causes their expression changes under drought stress. Our results unravelled a dual function of MdRAD5B in gene expression modulation in apple in response to drought, that is, via the regulation of chromatin remodelling and H3K27me3.

Fine-tuning of SUMOylation modulates drought tolerance of apple.

SUMOylation is involved in various aspects of plant biology, including drought stress. However, the relationship between SUMOylation and drought stress tolerance is complex; whether SUMOylation has a crosstalk with ubiquitination in response to drought stress remains largely unclear. In this study, we found that both increased and decreased SUMOylation led to increased survival of apple (Malus × domestica) under drought stress: both transgenic MdSUMO2A overexpressing (OE) plants and MdSUMO2 RNAi plants exhibited enhanced drought tolerance. We further confirmed that MdDREB2A is one of the MdSUMO2 targets. Both transgenic MdDREB2A OE and MdDREB2AK192R OE plants (which lacked the key site of SUMOylation by MdSUMO2A) were more drought tolerant than wild-type plants. However, MdDREB2AK192R OE plants had a much higher survival rate than MdDREB2A OE plants. We further showed SUMOylated MdDREB2A was conjugated with ubiquitin by MdRNF4 under drought stress, thereby triggering its protein degradation. In addition, MdRNF4 RNAi plants were more tolerant to drought stress. These results revealed the molecular mechanisms that underlie the relationship of SUMOylation with drought tolerance and provided evidence for the tight control of MdDREB2A accumulation under drought stress mediated by SUMOylation and ubiquitination.

Water quality induced corrosion of stainless steel valves during long-term service in a reverse osmosis system.

The current study analyzes the contribution of 10 water quality parameters (including pH, turbidity, conductivity, total dissolved solids (TDS), hardness, total organic carbon (TOC), alkalinity, calcium ions, chlorides and sulfates) to corrosion extent of stainless steel valves taken from different locations in a reverse osmosis system of a reclaimed water plant. The valves were in service for 5 years. Raman spectroscopy and X-ray photoelectron spectroscopy analyses are conducted to quantify corrosion products on different valves under various water quality conditions. On that basis, bivariate and multivariate regression analyses between the 10 water quality parameters and the corrosion extent of valve specimens (represented by metal loss percentage (MLP) values) are carried out to check the contribution of those water quality parameters to MLP. The results indicate that the proportions of metal oxides as corrosion products vary according to the corrosion extent of the valves. Although no linear correlation is found, all 10 water quality parameters except for pH show a significant positive correlation with the MLP values of the valve specimens. Moreover, results of multivariate regression suggest that the variation of MLP can be explained by turbidity, TDS, TOC and sulfates. A positive contribution of turbidity, TDS and TOC to MLP is observed, whereas the contribution of sulfates is negative. The results from the current work help to identify the reasons for water quality-induced failure of stainless steel equipment in RO systems.

Vasorin exocytosed from glioma cells facilitates angiogenesis via VEGFR2/AKT signaling pathway.

Glioma is a highly vascularized tumor of the central nervous system. Angiogenesis plays a predominant role in glioma progression and is considered an important therapeutic target. Our previous study showed that vasorin (VASN), a transmembrane protein, is overexpressed in glioma and promotes angiogenesis; however, the potential mechanism remains unclear. In this study, we found that human vascular endothelial cells (hECs) co-cultured with VASN-overexpressing glioma cells exhibited accelerated migration ability and increased expression of VASN originated from glioma cells. VASN was found in exosomes secreted by glioma cells and could be taken up by hECs. hECs showed more edge filopodia and significantly upregulated expression of endothelial tip cell marker gene and protein levels after co-culture with VASN-overexpressing glioma cells. In clinical glioma tissue and orthotopic transplantation glioma tissue, the vascular density and the number of vascular endothelial cells with a tip cell phenotype in VASN-overexpressed tissues were significantly higher than in tissues with low expression. At the molecular level, VASN interacted with VEGFR2 and caused internalization and autophosphorylation of VEGFR2 protein, and then activated the AKT signaling pathway. Our study collectively reveals the function and mechanism of VASN in facilitating angiogenesis in glioma, providing a new therapeutic target for glioma. Implications: These findings demonstrate that VASN exocytosed from glioma cells enhanced the migration of vascular endothelial cells by VEGFR2/AKT signaling pathway.

Interfering small ubiquitin modifiers (SUMO) improves the thermotolerance of apple by facilitating the activity of MdDREB2A.

Heat stress, which is caused by global warming, threatens crops yield and quality across the world. As a kind of post-translation modification, SUMOylation involves in plants heat stress response with a rapid and wide pattern. Here, we identified small ubiquitin modifiers (SUMO), which affect drought tolerance in apple, also participated in thermotolerance. Six isoforms of SUMOs located on six chromosomes in apple genome, and all the SUMOs were up-regulated in response to heat stress condition. The MdSUMO2 RNAi transgenic apple plants exhibited higher survival rate, lower ion leakage, higher catalase (CAT) activity, and Malondialdehyde (MDA) content under heat stress. MdDREB2A, the substrate of MdSUMO2 in apple, was accumulated in MdSUMO2 RNAi transgenic plants than the wild type GL-3 at the protein level in response to heat stress treatment. Further, the inhibited SUMOylation level of MdDREB2A in MdSUMO2 RNAi plants might repress its ubiquitination, too. The accumulated MdDREB2A in MdSUMO2 RNAi plants further induced heat-responsive genes expression to strengthen plants thermotolerance, including MdHSFA3, MdHSP26.5, MdHSP18.2, MdHSP70, MdCYP18-1 and MdTLP1. In summary, these findings illustrate that interfering small ubiquitin modifiers (SUMO) in apple improves plants thermotolerance, partly by facilitating the stability and activity of MdDREB2A.

Insights into the molecular mechanisms underlying responses of apple trees to abiotic stresses.

Apple (Malus[Formula: see text]domestica) is a popular temperate fruit crop worldwide. However, its growth, productivity, and quality are often adversely affected by abiotic stresses such as drought, extreme temperature, and high salinity. Due to the long juvenile phase and highly heterozygous genome, the conventional breeding approaches for stress-tolerant cultivars are time-consuming and resource-intensive. These issues may be resolved by feasible molecular breeding techniques for apples, such as gene editing and marker-assisted selection. Therefore, it is necessary to acquire a more comprehensive comprehension of the molecular mechanisms underpinning apples' response to abiotic stress. In this review, we summarize the latest research progress in the molecular response of apples to abiotic stressors, including the gene expression regulation, protein modifications, and epigenetic modifications. We also provide updates on new approaches for improving apple abiotic stress tolerance, while discussing current challenges and future perspectives for apple molecular breeding.

Cold shock protein 3 plays a negative role in apple drought tolerance by regulating oxidative stress response.

As RNA chaperones, cold shock proteins (CSPs) are essential for cold adaptation. Although the functions of CSPs in cold response have been demonstrated in several species, the roles of CSPs in response to drought are largely unknown. Here, we demonstrated that MdCSP3, a downstream target gene of MdMYB88 and MdMYB124, contributes to drought tolerance in apple (Malus × domestica). MdCSP3 responds to various abiotic stresses, including drought, cold, heat, and salt stress. Compared with non-transgenic apple GL-3, the MdCSP3 overexpressing plants exhibit significantly lower drought resistance and a reduced capacity for ROS scavenging by the regulation of antioxidant enzymes SOD, CAT, and POD. Additionally, RNA-seq data shows that MdCSP3 regulates expression of genes involved in oxidative stress response. Taken together, our results demonstrate the functions of MdCSP3 in apple drought tolerance, and this finding provides a new direction for breeding of drought resistant apple.