Integrative genomic and transcriptomic analysis for pinpointing recurrent alterations of plant homeodomain genes and their clinical significance in breast cancer

A wide range of the epigenetic effectors that regulate chromatin modification, gene expression, genomic stability, and DNA repair contain structurally conserved domains called plant homeodomain (PHD) fingers. Alternations of several PHD finger-containing proteins (PHFs) due to genomic amplification, mutations, deletions, and translocations have been linked directly to various types of cancer. However, little is known about the genomic landscape and the clinical significance of PHFs in breast cancer. Hence, we performed a large-scale genomic and transcriptomic analysis of 98 PHF genes in breast cancer using TCGA and METABRIC datasets and correlated the recurrent alterations with clinicopathological features and survival of patients. Different subtypes of breast cancer had different patterns of copy number and expression for each PHF. We identified a subset of PHF genes that was recurrently altered with high prevalence, including PYGO2 (pygopus family PHD finger 2), ZMYND8 (zinc finger, MYND-type containing 8), ASXL1 (additional sex combs like 1) and CHD3 (chromodomain helicase DNA binding protein 3). Copy number increase and overexpression of ZMYND8 were more prevalent in Luminal B subtypes and were significantly associated with shorter survival of breast cancer patients. ZMYND8 was also involved in a positive feedback circuit of the estrogen receptor (ER) pathway, and the expression of ZMYND8 was repressed by the bromodomain and extra terminal (BET) inhibitor in breast cancer. Our findings suggest a promising avenue for future research—to focus on a subset of PHFs to better understand the molecular mechanisms and to identify therapeutic targets in breast cancer

Remineralization Efficacy of an Amelogenin-Based Synthetic Peptide on Carious Lesions

Objective: The aim of this study was to evaluate the remineralization efficacy of an amelogenin-based peptide on initial enamel carious lesions in vitro. Furthermore, we attempted to provide insights into the possible mechanism of the remineralization, including determining the calcium-binding properties of the peptide and its effects on calcium phosphate mineralization.Methods: The peptide comprising the N-terminus and the C-terminus of porcine amelogenin was synthesized by Synpeptide Co., Ltd. Fifty specimens were randomly assigned to five immersing treatment groups for 12 days: remineralizing medium only; 12.5 μg/mL peptide + remineralizing medium; 25 μg/mL peptide + remineralizing medium; 50 μg/mL peptide + remineralizing medium; fluoride + remineralizing medium. After immersion, mean mineral loss before and after remineralization of each specimen was determined using micro-CT. Mean mineral gain after remineralization was calculated. Calcium binding properties were measured by Isothermal titration calorimetry (ITC). TEM and Fourier transform-infrared were used to determine the effects of the peptide on calcium phosphate mineralization.Results: A significant decrease in mineral loss after remineralization process in all groups was observed (p < 0.05). Treatment in remineralizing medium resulted in the lowest mineral gain while the fluoridated treatment exhibited the highest mineral gain among all groups. Inclusion of synthetic peptide in the remineralizing medium exhibited a higher mineral gain and the gain of 50 μg/mL group was greater than that of the 25 μg/mL group. No significant difference in mineral gain was observed between the remineralizing medium only group and the 12.5 μg/mL peptide group (p > 0.05). ITC values showed that the Ca2+-binding affinity of the peptide is about 9.914 × 104M−1. Furthermore, the peptide was found to inhibit calcium phosphate precipitation and stabilize amorphous calcium phosphate formation for more than 2 h and finally transform into ordered hydroxyapatite crystals.Conclusion: Specific concentrations of the amelogenin-based synthetic peptide promoted in vitro remineralization, with higher concentrations exhibiting significantly greater remineralization. This study presented evidence suggesting that the peptide may act as a Ca2+carrier as well as a regulating factor. When the stabilizing calcium and phosphorus ions bind with the peptide they become biologically available for the remineralization of deeper carious lesions, while also regulated by the peptide to transform into ordered hydroxyapatite crystals

Bio-priming of banana tissue culture plantlets with endophytic Bacillus velezensis EB1 to improve Fusarium wilt resistance

Tissue culture techniques have been routinely used for banana propagation and offered rapid production of planting materials with favorable genotypes and free of pathogenic microorganisms in the banana industry. Meanwhile, extensive scientific work suggests that micropropagated plantlets are more susceptible to Fusarium oxysporum f. sp. cubense (Foc), the deadly strain that causes Fusarium wilt of bananas than conventional planting material due to the loss of indigenous endophytes. In this study, an endophytic bacterium Bacillus velezensis EB1 was isolated and characterized. EB1 shows remarkable in vitro antagonistic activity against Foc with an inhibition rate of 75.43% and induces significant morphological and ultrastructural changes and alterations in the hyphae of Foc. Colony-forming unit (c.f.u.) counting and scanning electron microscopy (SEM) revealed that EB1 could colonize both the surface and inner tissues of banana tissue culture plantlets. Banana tissue culture plantlets of late rooting stage bioprimed with EB1 could efficiently ward off the invasive of Foc. The bio-priming effect could maintain in the acclimatized banana plants and significantly decrease the disease severity of Fusarium wilt and induce strong disease resistance by manipulating plant defense signaling pathways in a pot experiment. Our results provide the adaptability and potential of native endophyte EB1 in protecting plants from pathogens and infer that banana tissue culture plantlets bio-priming with endophytic microbiota could be a promising biological solution in the fight against the Fusarium wilt of banana

Association of exosomes with viral infection and hepatitis B virus-related liver diseases

Hepatitis B virus (HBV) infection causes pathological changes of the liver, including liver inflammation, hepatocyte necrosis, and even liver fibrosis, and promotes the progression from chronic hepatitis to liver cirrhosis and liver cancer, but related mechanisms remain unclear. The mechanism for the interaction between hepatocytes infected by HBV and uninfected hepatocytes/host immune system might be exosomes-mediated cell-cell communication in liver microenvironment. Many studies have demonstrated that viral infection can regulate the production of exosomes and affect their composition, and viral microRNAs, proteins, and even the entire virion can be incorporated into the exosomes, which can affect the immune recognition of viruses or regulate the function of adjacent cells. This article elaborates on the production and composition of exosomes and their roles in viral infection, as well as the research advances in the association between exosomes and HBV infection

Mechanistic Insights into Stereospecific Antifungal Activity of Chiral Fungicide Prothioconazole against <i>Fusarium oxysporum</i> F. sp. <i>cubense</i>

As a typical triazole fungicide, prothioconazole (Pro) has been used extensively due to its broad spectrum and high efficiency. However, as a racemic mixture of two enantiomers (R-Pro and S-Pro), the enantiomer-specific outcomes on the bioactivity have not been fully elucidated. Here, we investigate how chirality affects the activity and mechanism of action of Pro enantiomers on Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4), the notorious virulent strain causing Fusarium wilt of banana (FWB). The Pro enantiomers were evaluated in vivo and in vitro with the aid of three bioassay methods for their fungicidal activities against TR4 and the results suggested that the fungicidal activities of Pro enantiomers are stereoselective in a dose-dependent manner with R-Pro making a major contribution to the treatment outcomes. We found that R-Pro led to more severe morphological changes and impairment in membrane integrity than S-Pro. R-Pro also led to the increase of more MDA contents and the reduction of more SOD and CAT activities compared with the control and S-Pro groups. Furthermore, the expression of Cytochrome P450 14α-sterol demethylases (CYP51), the target for triazole fungicides, was significantly increased upon treatment with R-Pro rather than S-Pro, at both transcriptional and translational levels; so were the activities of the Cytochrome P450 enzymes. In addition, surface plasmon resonance (SPR) and molecular docking illuminated the stereoselective interactions between the Pro enantiomers and CYP51 of TR4 at the target site, and R-Pro showed a better binding affinity with CYP51 than S-Pro. These results suggested an enantioselective mechanism of Pro against TR4, which may rely on the enantioselective damages to the fungal cell membrane and the enantiospecific CYP51 binding affinity. Taken together, our study shed some light on the mechanisms underlying the differential activities of the Pro enantiomers against TR4 and demonstrated that Pro can be used as a potential candidate in the treatment of FWB

LncRNA NORAD promotes the progression of myocardial infarction by targeting the miR-22-3p/PTEN axis

NORAD is a newly identified long non-coding RNA (lncRNA) that plays an important role in cancers. NORAD has been found to be highly expressed in the mouse model of acute myocardial infarction (AMI). However, the role of NORAD in the regulation of AMI remains unknown. In the present study, we aimed to investigate the function of NORAD in AMI and explore the potential regulatory mechanisms. A mouse model of AMI was established and NORAD was knocked-down. The infarcted size of heart tissues and the cardiac function were evaluated. In addition, two cardiomyocyte cell lines were treated with hypoxia/re-oxygenation (H/R) to mimic AMI in vitro. Luciferase reporter assay, RNA pull-down assay, fluorescence in situ hybridization, qRT-PCR, and western blot analysis were performed. Apoptotic cells and the levels of L-lactate dehydrogenase (LDH) and malondialdehyde (MDA) were detected. Our results show that downregulation of NORAD efficiently attenuates heart damage in the AMI mouse model. NORAD interacts with miR-22-3p. Knock-down of NORAD inhibits H/R-induced cell apoptosis and reduces LDH and MDA levels, while its effects are abolished by miR-22-3p inhibitor. MiR-22-3p interacts with PTEN and inhibits its expression. Overexpression of miR-22-3p inhibits H/R-induced cell apoptosis and reduces LDH and MDA levels, while its effects are abolished by overexpression of PTEN. Finally, overexpression of NORAD inhibits the AKT/mTOR signaling pathway, and its effects are attenuated by overexpression of miR-22-3p. Taken together, our study reveals that NORAD promotes the progression of AMI by regulating the miR-22-3p/PTEN axis, and the AKT/mTOR signaling may also be involved in the regulatory processes

Petrological and geochemical characteristics of the Wanganzhen complex and discussion on its genesis

The Wanganzhen complex is one of representative example of Taihang-Da Hinggan tectonomagmatic belt in eastern China, which as the largest scale adn the most rock types. It consists of three-stage rocks. According to the major element, trace element, REE and ND, SR, PB isotopic characteristics of the Wanganzhen complex reported in this paper, the main stage rocks (Granodiorite, adamellite, and few quartz diorite) have similar petrological and geochemical characteristics to those of adakite with SiO₂≥58%, Al₂O₃≥15%, low Y content (4.20~12.68μg/g), high SR content (518~861μg/g) and Sr/Y ratios (60.19~178.10), LREE enrichment with (La/Yb)N=34.06~76.91, HREE depletion with Yb=.044~1.00, no obviously Eu anomaly (Eu/Eu*=0.83~1.03), and relative depletion in the high field strength elements (such as Nb, Hf, Ti), I(Sr)=0.7060, negative εNd(t) value (-16.29~-14.27) and positive εSr(t) value (+23.7~+25.0), but obviously different from those of subduction-related adakites. These adakite-like rocks were most likely derived from the partial melting of basaltic lower crust in the thickened crust resulted from hot mantle material upwellins as several mushroom cloud and the thermally altered ground uplifting to the bottom of continental crust during late Jurassic period. But the early and the late stage ones belong to non-adakites. The early basic- to intermediate- instrusive rocks (hornblendite, gabbroite and diorite) are high Mg and Fe, LREE enrichment, EU positive anomaly, enriched in compatible elements and low incompatible elements, I(Sr)=0.7056, εNd(t)=-16.72~-10.92, which are the products of partial melting of subcontinental lithospheric enrich mantle and probably represent the underplating basaltic magma below the thickened continental crust during early Mesozoic era. The late alkaline intermediate to acid-intrusive rocks (alkali-granite, quartz syenite and quartz monzonite) are characteristic of high K and Na alkaline series and high ΣREE, negative Eu anomaly, low Sr content, high Y and Yb, negative Sr anomaly, I(Sr)=0.7062, εNd(t)=-16.25, suggesting that the formation of adakite-like rocks of the main stage result in the lithospheric delamination and cause asthenosphere to upwell to the bottom of thinned continental crust, so the rocks of the late stage are formed by the partial melting of the materials in the crust-mantle transformation belt even in the middle crust. In this paper the Rb-Sr isochronal age of granodiorite (145.7±5.3Ma) is reported. Based on the Rb-Sr isochronal age of granite and granidiorite, the main body of the Wanganzhen complex was probably formed in late Jurrasic period between 137.8Ma and 145.6Ma

Alkaline intrusives at the east foot of the Taihang-Da Hinggan Mountains; chronology, Sr, Nd and Pb isotopic characteristics and their implications

Based on the Rb-Sr isochron dating results, this paper suggests that the alkaline intrusive belt at the east foot of the Taihang-Da Hinggan Mountains were formed between 135 and 122 Ma. And the alkaline intrusives in the north and south sections of this belt have entirely different Sr, Nd and Pb isotopic characteristics, i.e., all the rocks in the south section have positive ɛSr(t) and negative ɛNd(t) values and all those in the north have the opposite values. On the ɛSr(t) versus ɛNd(t) correlation diagram, the samples from the south are concentrated along the enriched mantle evolution trend lines and nearby, while those from the north fall along the depleted mantle trend lines and nearby. On the Pb isotope composition diagram, most of the samples from the south section fall on the mantle Pb evolution line and nearby, while those from the north lie between the Pb evolution lines of the mantle and the orogenic belt. The above-stated isotopic characteristics not only indicate that the source rocks of the alkaline intrusives in the south section have a close connection to materials from the enriched mantle reservoir, while those in the north are related to materials from the depleted one, but also reveal that the upper mantle below the North China platform is enriched and that below the Inner Mongolia geosyncline is depleted