Unsupervised deep learning model for correcting Nyquist ghosts of single-shot spatiotemporal encoding.

PURPOSE: To design an unsupervised deep learning (DL) model for correcting Nyquist ghosts of single-shot spatiotemporal encoding (SPEN) and evaluate the model for real MRI applications. METHODS: The proposed method consists of three main components: (1) an unsupervised network that combines Residual Encoder and Restricted Subspace Mapping (RERSM-net) and is trained to generate a phase-difference map based on the even and odd SPEN images; (2) a spin physical forward model to obtain the corrected image with the learned phase difference map; and (3) cycle-consistency loss that is explored for training the RERSM-net. RESULTS: The proposed RERSM-net could effectively generate smooth phase difference maps and correct Nyquist ghosts of single-shot SPEN. Both simulation and real in vivo MRI experiments demonstrated that our method outperforms the state-of-the-art SPEN Nyquist ghost correction method. Furthermore, the ablation experiments of generating phase-difference maps show the advantages of the proposed unsupervised model. CONCLUSION: The proposed method can effectively correct Nyquist ghosts for the single-shot SPEN sequence.

Differentiation of malignant from benign pleural effusions based on artificial intelligence.

INTRODUCTION: This study aimed to construct artificial intelligence models based on thoracic CT images to perform segmentation and classification of benign pleural effusion (BPE) and malignant pleural effusion (MPE). METHODS: A total of 918 patients with pleural effusion were initially included, with 607 randomly selected cases used as the training cohort and the other 311 as the internal testing cohort; another independent external testing cohort with 362 cases was used. We developed a pleural effusion segmentation model (M1) by combining 3D spatially weighted U-Net with 2D classical U-Net. Then, a classification model (M2) was built to identify BPE and MPE using a CT volume and its 3D pleural effusion mask as inputs. RESULTS: The average Dice similarity coefficient, Jaccard coefficient, precision, sensitivity, Hausdorff distance 95% (HD95) and average surface distance indicators in M1 were 87.6±5.0%, 82.2±6.2%, 99.0±1.0%, 83.0±6.6%, 6.9±3.8 and 1.6±1.1, respectively, which were better than those of the 3D U-Net and 3D spatially weighted U-Net. Regarding M2, the area under the receiver operating characteristic curve, sensitivity and specificity obtained with volume concat masks as input were 0.842 (95% CI 0.801 to 0.878), 89.4% (95% CI 84.4% to 93.2%) and 65.1% (95% CI 57.3% to 72.3%) in the external testing cohort. These performance metrics were significantly improved compared with those for the other input patterns. CONCLUSIONS: We applied a deep learning model to the segmentation of pleural effusions, and the model showed encouraging performance in the differential diagnosis of BPE and MPE.

Unsupervised cycle-consistent network using restricted subspace field map for removing susceptibility artifacts in EPI.

PURPOSE: To design an unsupervised deep neural model for correcting susceptibility artifacts in single-shot Echo Planar Imaging (EPI) and evaluate the model for preclinical and clinical applications. METHODS: This work proposes an unsupervised cycle-consistent model based on the restricted subspace field map to take advantage of both the deep learning (DL) and the reverse polarity-gradient (RPG) method for single-shot EPI. The proposed model consists of three main components: (1) DLRPG neural network (DLRPG-net) to obtain field maps based on a pair of images acquired with reversed phase encoding; (2) spin physical model-based modules to obtain the corrected undistorted images based on the learned field map; and (3) cycle-consistency loss between the input images and back-calculated images from each cycle is explored for network training. In addition, the field maps generated by DLRPG-net belong to a restricted subspace, which is a span of predefined cubic splines to ensure the smoothness of the field maps and avoid blurring in the corrected images. This new method is trained and validated on both preclinical and clinical datasets for diffusion MRI. RESULTS: The proposed network could effectively generate smooth field maps and correct susceptibility artifacts in single-shot EPI. Simulated and in vivo preclinical/clinical experiments demonstrated that our method outperforms the state-of-the-art susceptibility artifact correction methods. Furthermore, the ablation experiments of the cycle-consistent network and the restricted subspace in generating field maps did show the advantages of DLRPG-net. CONCLUSION: The proposed method (DLRPG-net) can effectively correct susceptibility artifacts for preclinical and clinical single-shot EPI sequences.

Surgical and medical co-management optimizes surgical outcomes in older patients with chronic diseases undergoing robot-assisted laparoscopic radical prostatectomy.

INTRODUCTION: While robotic-assisted laparoscopic radical prostatectomy (RRP) is a standard mode for localized prostate cancer (PC), the risk of complications in older patients with chronic diseases and complex medical conditions can be a deterrent to surgery. Surgical and medical co-management (SMC) is a new strategy to improve patients' healthcare outcomes in surgical settings. METHODS: We reviewed the clinical data of older patients with chronic diseases who were cared for with SMC undergoing RRP in our hospital in the past 3 years and compared them with the clinical data from the general urology ward. Preoperative conditions and related indicators of recovery, and incidence of postoperative complications with the Clavien Grade System were compared between these two groups. RESULTS: The indicators of recovery were significantly better, and the incidence rates of complications were significantly reduced in the SMC group at grades I-IV (p < 0.05), as compared to the general urology ward group. CONCLUSIONS: The provision of care by SMC for older patients focused on early identification, comorbidity management, preoperative optimization, and collaborative management would significantly improve surgical outcomes. The SMC strategy is worthy of further clinical promotion in RRP treatment in older men with chronic diseases and complex medical conditions.

Synthesis of pendant fullerene dimers by an aminomethylation reaction of fulleropyrrolidines bearing ketone moieties.

An aminomethylation reaction of fulleropyrrolidines bearing ketone moieties in the presence of N-unsubstituted fulleropyrrolidines and paraformaldehyde with the aid of p-toluenesulfonic acid afforded a series of scarce pendant fullerene dimers. A simple change of reaction substrates from ketone to ketone-containing fulleropyrrolidines successfully realized the synthesis of a variety of novel pendant fullerene dimers, including those from methyl ketone-containing fulleropyrrolidines, which were considered to produce the known bridged fullerene dimers. It should be noted that pendant fullerene dimers are usually difficult to prepare by other methods and may have promising applications in perovskite solar cells. Density functional theory (DFT) has been employed to elucidate the regioselectivity of methyl ketone-containing fulleropyrrolidines to yield exclusively pendant fullerene dimers by investigating the Gibbs free energy profile of the reaction starting from methyl ketone-containing fulleropyrrolidines and iminium intermediates.

Integrated Cytological, Physiological, and Transcriptome Analyses Provide Insight into the Albino Phenotype of Chinese Plum (Prunus salicina).

Albino seedlings that arise during seed reproduction can have a significant impact on plant growth and breeding. In this research, we present the first report of albino occurrences in the seed reproduction process of Prunus salicina and describe the cytological, physiological, and transcriptomic changes observed in albino seedlings. The albino seedlings which were observed in several plum cultivars exhibited abnormal chloroplast ultrastructure and perturbed stomatal structure. Compared to normal seedlings, the photosynthetic pigment contents in albino seedlings decreased by more than 90%, accompanied by significant reductions in several chlorophyll fluorescence parameters. Furthermore, substantially changed photosynthetic parameters indicated that the photosynthetic capacity and stomatal function were impaired in albino seedlings. Additionally, the activities of the antioxidant enzyme were drastically altered against the background of higher proline and lower ascorbic acid in leaves of albino seedlings. A total of 4048 differentially expressed genes (DEGs) were identified through transcriptomic sequencing, and the downregulated DEGs in albino seedlings were greatly enriched in the pathways for photosynthetic antenna proteins and flavonoid biosynthesis. GLK1 and Ftsz were identified as candidate genes responsible for the impaired chloroplast development and division in albino seedlings. Additionally, the substantial decline in the expression levels of examined photosystem-related chloroplast genes was validated in albino seedlings. Our findings shed light on the intricate physiological and molecular mechanisms driving albino plum seedling manifestation, which will contribute to improving the reproductive and breeding efforts of plums.

Genome-Wide Identification and Characterization of Gibberellic Acid-Stimulated Arabidopsis Gene Family in Pineapple (Ananas comosus).

The gibberellic acid-stimulated Arabidopsis (GASA) gene family plays a crucial role in growth, development, and stress response, and it is specific to plants. This gene family has been extensively studied in various plant species, and its functional role in pineapple has yet to be characterized. In this study, 15 AcGASA genes were identified in pineapple through a genome-wide scan and categorized into three major branches based on a phylogenetic tree. All AcGASA proteins share a common structural domain with 12 cysteine residues, but they exhibit slight variations in their physicochemical properties and motif composition. Predictions regarding subcellular localization suggest that AcGASA proteins are present in the cell membrane, Golgi apparatus, nucleus, and cell wall. An analysis of gene synteny indicated that both tandem and segmental repeats have a significant impact on the expansion of the AcGASA gene family. Our findings demonstrate the differing regulatory effects of these hormones (GA, NAA, IAA, MeJA, and ABA) on the AcGASA genes. We analyzed the expression profiles of GASA genes in different pineapple tissue parts, and the results indicated that AcGASA genes exhibit diverse expression patterns during the development of different plant tissues, particularly in the regulation of floral organ development. This study provides a comprehensive understanding of GASA family genes in pineapple. It serves as a valuable reference for future studies on the functional characterization of GASA genes in other perennial herbaceous plants.

Retrospective motion correction for preclinical/clinical magnetic resonance imaging based on a conditional generative adversarial network with entropy loss.

Multishot scan magnetic resonance imaging (MRI) acquisition is inherently sensitive to motion, and motion artifact reduction is essential for improving the image quality in MRI. This work proposes and validates a new end-to-end motion-correction method for the multishot sequence that incorporates a conditional generative adversarial network with minimum entropy (cGANME) of MR images. The cGANME contains an encoder-decoder generator to obtain motion-corrected images and a PatchGAN discriminator to classify the image as either real (motion-free) or fake (motion-corrected). The entropy of the images is set as one loss item in the cGAN's loss as the entropy increases monotonically with the motion artifacts. An ablation experiment of the different weights of entropy loss was performed to evaluate the function of entropy loss. The preclinical dataset was acquired with a fast spin echo pulse sequence on a 7.0-T scanner. After the simulation, we had 10,080/2880/1440 slices for training, testing, and validating, respectively. The clinical dataset was downloaded from the Human Connection Project website, and 11,300/3500/2000 slices were used for training, testing, and validating after simulation, respectively. Extensive experiments for different motion patterns, motion levels, and protocol parameters demonstrate that cGANME outperforms traditional and some state-of-the-art, deep learning-based methods. In addition, we tested cGANME on in vivo awake rats and mitigated the motion artifacts, indicating that the model has some generalizability.

Fine Particulate Matter Triggers α-Synuclein Fibrillization and Parkinson-like Neurodegeneration.

BACKGROUND: The deposition of α-synuclein (α-Syn) in the brain is the pathological hallmark of Parkinson's disease (PD). Epidemiological data indicate that exposure to fine particulate matter (≤2.5 µm in aerodynamic diameter [PM2.5]) is associated with an increased risk for PD. OBJECTIVE: The aim of this study is to investigate whether PM2.5 has a direct effect on α-Syn pathology and how it drives the risk for PD. METHODS: PM2.5 was added into α-Syn monomers and different cell models to test whether PM2.5 can promote the fibrillization and aggregation of α-Syn. α-Syn A53T transgenic mice and α-Syn knockout mice were used to investigate the effects of PM2.5 on PD-like pathology. RESULTS: PM2.5 triggers the fibrillization of α-Syn and promotes the formation of α-Syn fibrils with enhanced seeding activity and neurotoxicity. PM2.5 also induces mitochondrial dysfunction and oxidative stress. Intrastriatal injection or intranasal administration of PM2.5 exacerbates α-Syn pathology and dopaminergic neuronal degeneration in α-Syn A53T transgenic mice. The detrimental effect of PM2.5 was attenuated in α-Syn knockout mice. CONCLUSIONS: Our results identify that PM2.5 exposure could promote the α-Syn pathology, providing mechanistic insights into how PM2.5 increases the risk for PD. © 2022 International Parkinson and Movement Disorder Society.

Multimodal Imaging Response after the Singular or Combination Treatments of Vascular Endothelial Growth Factor Inhibitor and Immune Checkpoint Inhibitor.

This study aims to dynamically assess tumor changes after variable treatments with vascular endothelial growth factor (VEGF) inhibitor and/or immune checkpoint inhibitor (ICI) using multimodal imaging of MRI and 18F-FDG PET/CT in a hepatocellular carcinoma (HCC) mice model. Based on different treatments, 24 mice were randomly divided into four groups: control (isotype-matched IgG antibody 10 mg/kg), VEGF inhibitor (sorafenib 50 mg/kg), ICI (anti-PD-L1 antibody 10 mg/kg), and combination groups (sorafenib 50 mg/kg + anti-PD-L1 antibody 10 mg/kg). Quantitative imaging assessments, including volume transfer constant (Ktrans), apparent diffusion coefficient (ADC), lactate/choline ratio, and the maximum standardized 18F-FDG uptake value ratio of tumor to muscle (SUVtumor/SUVmuscle ratio), were acquired at different time points (before treatment and 7, 14, and 21 days after treatment). Quantitative data were presented as the mean ± standard errors and two-way repeated-measure ANOVA tests were performed for intergroup and intertime point comparisons. After 21 days from the initiation of therapies, combination group showed the lowest tumor volume and weight, followed by ICI, VEGF inhibitor, and control group, with no significance between the VEGF inhibitor and control groups. In addition, Ktrans values significantly decreased, and the lactate/choline ratio and SUVtumor/SUVmuscle ratio were significantly elevated in the VEGF inhibitor group. ADC significantly increased in the ICI and combination groups, with no significant differences in ADC observed between the control and VEGF inhibitor groups, which showed a similar dynamic change to the tumor volume. Furthermore, Ktrans, lactate/choline ratio, and ADC were significantly correlated with CD31+ area, hypoxyprobe+ area, and apoptosis, respectively. Our results suggest that the singular treatment and combination of the VEGF inhibitor and ICI treatments for HCC present different multimodal imaging changes in accordance with the specific histopathological features. These findings might facilitate the formulation of better treatment response criteria; besides, we find ADC is probably an indicator easily to obtain for treatment response evaluation.

Sea urchin-like CoNi2S4materials derived from nickel hexamyanocobaltate for high-performance asymmetric hybrid supercapacitor.

In this work, a mild chemical precipitation method and simple hydrothermal treatment of the nickel hexamyanocobaltate precursor strategy are developed to prepare a sea urchin-like CoNi2S4compound with remarkable specific capacity and excellent cycling stability. The prepared CoNi2S4has an outstanding specific capacity of 149.1 mA h g-1at 1 A g-1and an initial capacity of 83.1% after 3000 cycles at 10 A g-1. Moreover, the porous carbon nanospheres (PCNs) with exhibit cycling stability (94.7% of initial specific capacity after 10 000 cycles at 10 A g-1) are selected as negative electrode to match CoNi2S4positive electrode for assembly of CoNi2S4//PCNs asymmetric supercapacitor (ASC). Satisfactorily, the as-assembled CoNi2S4//PCNs ASC exhibits an impressive energy density of 41.6 Wh kg-1at 797 W kg-1, as well as the suitable capacity retention of 82.8% after 10 000 cycles. The superior properties of the device demonstrated that the as-prepared material is potential energy storage material.

Systematic Investigations on the Metabolic and Transcriptomic Regulation of Lactate in the Human Colon Epithelial Cells.

Lactate, primarily produced by the gut microbiota, performs as a necessary "information transmission carrier" between the gut and the microbiota. To investigate the role of lactate in the gut epithelium cell-microbiota interactions as a metabolic signal, we performed a combinatory, global, and unbiased analysis of metabolomic and transcriptional profiling in human colon epithelial cells (Caco-2), using a lactate treatment at the physiological concentration (8 mM). The data demonstrated that most of the genes in oxidative phosphorylation were significantly downregulated in the Caco-2 cells due to lactate treatment. Consistently, the levels of fumarate, adenosine triphosphate (ATP), and creatine significantly decreased, and these are the metabolic markers of OXPHOS inhibition by mitochondria dysfunction. The one-carbon metabolism was affected and the polyol pathway was activated at the levels of gene expression and metabolic alternation. In addition, lactate significantly upregulated the expressions of genes related to self-protection against apoptosis. In conclusion, lactate participates in gut-gut microbiota communications by remodeling the metabolomic and transcriptional signatures, especially for the regulation of mitochondrial function. This work contributes comprehensive information to disclose the molecular mechanisms of lactate-mediated functions in human colon epithelial cells that can help us understand how the microbiota communicates with the intestines through the signaling molecule, lactate.

Rutin Inhibits Ox-LDL-Mediated Macrophage Inflammation and Foam Cell Formation by Inducing Autophagy and Modulating PI3K/ATK Signaling.

Atherosclerosis (AS) is one of the leading causes of death among the elderly, and is primarily caused by foam cell generation and macrophage inflammation. Rutin is an anti-inflammatory, anti-oxidant, anti-allergic, and antiviral flavonoid molecule, known to have anti-atherosclerotic and autophagy-inducing properties, but its biological mechanism remains poorly understood. In this study, we uncovered that rutin could suppress the generation of inflammatory factors and reactive oxygen species (ROS) in ox-LDL-induced M2 macrophages and enhance their polarization. Moreover, rutin could decrease foam cell production, as shown by oil red O staining. In addition, rutin could increase the number of autophagosomes and the LC3II/I ratio, while lowering p62 expression. Furthermore, rutin could significantly inhibit the PI3K/ATK signaling pathway. In summary, rutin inhibits ox-LDL-mediated macrophage inflammation and foam cell formation by inducing autophagy and modulating PI3K/ATK signaling, showing potential in treating atherosclerosis.

Antimony transformation and mobilization from stibnite by an antimonite oxidizing bacterium Bosea sp. AS-1.

Soils and waters are heavily contaminated by antimony in Xikuangshan (XKS) mine area. It is widely accepted that oxidative dissolution of sulfide minerals and aqueous dissolution are the most prevalent geochemical mechanisms for the release of Sb to the environment. Bosea sp. AS-1 is an antimonite-oxidizer isolated from the mine slag in Xikuangshan Sb mine. Whole genome sequencing revealed the presence of multiple sulfur-oxidizing genes, antimony (Sb) metabolism genes and carbon fixation genes in AS-1's genome. We therefore hypothesized that under oxic conditions, AS-1 could mediate the oxidation of sulfide and Sb(III) in stibnite (Sb2S3) and lead to the release of Sb. Indeed, strain AS-1 was discovered as an autotrophic Sb(III)-oxidizer. Antimony mobilization studies conducted with strain AS-1 showed significantly enhanced mobilization of Sb, and complete oxidation of released Sb and sulfur to Sb(V) and sulfate. In addition, AS-1 induced a faster release of Sb under heterotrophic condition, and new acicular minerals might form. These findings support the hypothesis that microorganisms play an important role in the mobilization and transformation of Sb in XKS mine area and may contribute to our further understanding of the Sb biogeochemical redox cycle in natural environment.

Exosome-mediated delivery of antisense oligonucleotides targeting α-synuclein ameliorates the pathology in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease. Pathologically, PD is characterized by the formation of Lewy bodies (LBs) in the brain, which mainly comprises phosphorylated and aggregated α-synuclein (α-syn). The aberrant aggregation of α-syn is believed to play a key role in the pathogenesis of PD. While α-syn expression can be reduced by antisense oligonucleotides (ASOs), the challenge to deliver ASOs safely and effectively into the neurons remains unresolved. Here, we developed a safe and highly effective ASO delivery method by using exosomes. We first identified the ASO sequence that selectively reduced α-syn expression: ASO4. Exosome-mediated delivery of ASO4 (exo-ASO4) showed high cellular uptake and low toxicity in primary neuronal cultures. Exo-ASO4 also significantly attenuated α-syn aggregation induced by pre-formed α-syn fibrils in vitro. Exo-ASO4 intracerebroventricular injection into the brains of α-syn A53T mice, a transgenic model of PD, significantly decreased the expression of α-syn and attenuated its aggregation. Furthermore, exo-ASO4 ameliorated the degeneration of dopaminergic neurons in these mice. Finally, the α-syn A53T mice showed significantly improved locomotor functions after exo-ASO4 injection. Overall, this study demonstrates that exosome-mediated ASO4 delivery may be an effective treatment option for PD.

Genetically Encoded Dual-Color Light-Up RNA Sensor Enabled Ratiometric Imaging of MicroRNA.

MicroRNAs (miRNAs) play essential roles in regulating gene expression and cell fate. However, it remains a great challenge to image miRNAs with high accuracy in living cells. Here, we report a novel genetically encoded dual-color light-up RNA sensor for ratiometric imaging of miRNAs using Mango as an internal reference and SRB2 as the sensor module. This genetically encoded sensor is designed by expressing a splittable fusion of the internal reference and sensor module under a single promoter. This design strategy allows synchronous expression of the two modules with negligible interference. Live cell imaging studies reveal that the genetically encoded ratiometric RNA sensor responds specifically to mir-224. Moreover, the sensor-to-Mango fluorescence ratios are linearly correlated with the concentrations of mir-224, confirming their capability of determining mir-224 concentrations in living cells. Our genetically encoded light-up RNA sensor also enables ratiometric imaging of mir-224 in different cell lines. This strategy could provide a versatile approach for ratiometric imaging of intracellular RNAs, affording powerful tools for interrogating RNA functions and abundance in living cells.

Robust water-fat separation based on deep learning model exploring multi-echo nature of mGRE.

PURPOSE: To design a new deep learning network for fast and accurate water-fat separation by exploring the correlations between multiple echoes in multi-echo gradient-recalled echo (mGRE) sequence and evaluate the generalization capabilities of the network for different echo times, field inhomogeneities, and imaging regions. METHODS: A new multi-echo bidirectional convolutional residual network (MEBCRN) was designed to separate water and fat images in a fast and accurate manner for the mGRE data. This new MEBCRN network contains 2 main modules, the first 1 is the feature extraction module, which learns the correlations between consecutive echoes, and the other one is the water-fat separation module that processes the feature information extracted from the feature extraction module. The multi-layer feature fusion (MLFF) mechanism and residual structure were adopted in the water-fat separation module to increase separation accuracy and robustness. Moreover, we trained the network using in vivo abdomen images and tested it on the abdomen, knee, and wrist images. RESULTS: The results showed that the proposed network could separate water and fat images accurately. The comparison of the proposed network and other deep learning methods shows the advantage in both quantitative metrics and robustness for different TEs, field inhomogeneities, and images acquired for various imaging regions. CONCLUSION: The proposed network could learn the correlations between consecutive echoes and separate water and fat images effectively. The deep learning method has certain generalization capabilities for TEs and field inhomogeneity. Although the network was trained only in vivo abdomen images, it could be applied for different imaging regions.

Activation of κ-opioid receptor inhibits inflammatory response induced by sodium palmitate in human umbilical vein endothelial cells.

OBJECTIVES: The current study aims to investigate the effect of κ-opioid receptor (κ-OR) activation on sodium palmitate (SP)-induced human umbilical vein endothelial cells (HUVECs) inflammatory response and elucidate the underlying mechanisms. METHODS: A hyperlipidemic cell model was established and treated with κ-OR agonist (U50,488H), and antagonist (norbinaltorphimine, nor-BNI), or inhibitors targeting PI3K, Akt or eNOS (LY294002, MK2206-2HCl or L-NAME, respectively). Furthermore, the expression levels of NLRP3, caspase-1, p-Akt, Akt, p-eNOS, and total eNOS were evaluated. Additionally, the production of reactive oxygen species, and levels of inflammatory factors, such as TNF-α, IL-1ß, IL-6, IL-1 and adhesion molecules, such as ICAM-1, VCAM-1, P-selectin, and E-selectin were determined. The adherence rates of the neutrophils and monocytes were assessed as well. RESULTS: The SP-induced hyperlipidemic cell model demonstrated increased expression of NLRP3 and caspase-1 proteins (P < 0.05) and elevated ROS levels (P < 0.01), and decreased phosphorylated-Akt and phosphorylated-eNOS expression (P < 0.05). In addition, SP significantly increased TNF-α, IL-1ß, IL-6, ICAM-1, VCAM-1, P-selectin, and E-selectin levels (P < 0.01), decreased IL-10 levels (P < 0.01), and increased the adhesion rates of monocytes and neutrophils (P < 0.01). The SP-induced inflammatory response in HUVECs was ameliorated by κ-OR agonist, U50,488H. However, the protective effect of U50,488H was abolished by κ-OR antagonist, nor-BNI, and inhibitors of PI3K, Akt and eNOS. CONCLUSION: Our findings suggest that κ-OR activation inhibits SP-induced inflammation by activating the PI3K/Akt/eNOS signaling pathway.

Exosomal microRNA-107 reverses chemotherapeutic drug resistance of gastric cancer cells through HMGA2/mTOR/P-gp pathway.

BACKGROUND: RNA cargo in exosomes, especially microRNAs (miRNAs), play an important role in the chemotherapy drug resistance of human cancers. However, the role and mechanism of exosomal miR-107 on multidrug resistance of gastric cancer cells was still not clear. In this study, we sought to explore whether exosomal miR-107 could reverse the resistance of gastric cancer cells to the chemotherapy drugs. METHODS: We extracted exosomes from sensitive (SGC-7901, MGC-803) and resistant (SGC-7901/5-FU) gastric cancer cells by ultracentrifugation and the isolated exosomes were identified using transmission electron microscopy (TEM) and dynamic light scattering analysis (DLS). The expression of miR-107 and high mobility group A2 (HMGA2) were detected by real-time quantitative PCR (RT-qPCR). MTT assay was used to investigate the effect of exosomes on gastric cancer cells growth in vitro. The uptake of exosomes by recipient cells were observed using a fluorescence microscope. The predicted target relationship between miR-107 and HMGA2 was verified by gauss-luciferase reporter assay. The expression of HMGA2, p-mTOR/mTOR, P-gp and other exosomal indicated marker proteins was detected by western blot. RESULTS: Our results indicated that the isolated exosomes were typically cup-like lipid bilayer membranes structure. SGC-7901/5-FU cells were cross-resistant to chemotherapy drug cisplatin (CDDP), and the sensitive cells-secreted exosomes drastically reversed the resistance of the resistant GC cells to the chemotherapeutic drugs, which was verified by exosomal inhibitor GW4896. Mechanistically, the reversal effect was mainly mediated by exosome-secreted miR-107 through downregulating the expression of target molecular HMGA2 and inhibiting HMGA2/mTOR/P-gp pathway, which were supported by results from luciferase reporter assay and rescue assay. CONCLUSIONS: These findings demonstrated that exosome-transmitted miR-107 significantly enhanced the sensitivity of resistant gastric cancer cells to chemotherapeutic agents by mediating the HMGA2/mTOR/P-gp axis and exosomal miR-107 may be a novel target in gastric cancers treatment.

Genome-wide identification and expression analysis of the MYB transcription factor in Japanese plum (Prunus salicina).

MYB proteins constitute one of the largest transcription factor families in plants, members of which are involved in various plant physiological and biochemical processes. Japanese plum (Prunus salicina) is one of the important stone fruit crops worldwide. To date, no comprehensive study of the MYB family in Japanese plum has been reported. In this study, we performed genome-wide analysis of MYB genes in Japanese plum including the phylogeny, gene structures, protein motifs, chromosomal locations, collinearity and expression patterns analysis. A total of 96 Japanese plum R2R3-MYB (PsMYB) genes were characterized and distributed on 8 chromosomes at various densities. Collinearity analysis indicated that the segmental duplication events played a crucial role in the expansion of PsMYB genes, and the interspecies synteny analysis revealed the orthologous gene pairs between Japanese plum and other four selected Rosaceae species. The 96 PsMYB genes could be classified into 27 subgroups based on phylogenetic topology, as supported by the conserved gene structures and motif compositions. Further comparative phylogenetic analysis revealed the functional divergence of MYB gene family during evolution, and three subgroups which included only Rasaceae MYB genes were identified. Expression analysis revealed the distinct expression profiles of the PsMYB genes, and further functional predictions found some of them might be associated with the plum fruit quality traits. Our researches provide a global insight into the organization, phylogeny, evolution and expression patterns of the PsMYB genes, and contribute to the greater understanding of their functional roles in Japanese plum.