Polyploid rice hybrids have a powerful biological and yield potential that may become a new way for rice breeding; however, low fertility is major hindrance in commercial utilization. Here, we developed a neo-tetraploid rice that could overcome the sterility of autotetraploid rice and produce high heterosis. Transcriptome analysis of F1 hybrid developed by crossing neo-tetraploid with autotetraploid rice displayed 807, 663 and 866 differentially expressed genes that uniquely associated with F1 and specific to (DEGFu-sp) anther, ovary and leaf, respectively. Of the DEGFu-sp, 1224 genes displayed nonadditive expression; 44 and 10 genes were annotated as TFs and methyltransferase or hydroxymethyltransferase, respectively. Gene ontology enrichment and co-expression analysis revealed specific differential gene expressions in the DEGFu-sp to leaf, anther and ovary, such as genes related to photosynthesis, metabolic process and transport, and co-expression network including fertility, resistance and epigenetic elements. Of the DEGFu-sp to anther, 42 meiosis stage-specific genes, eight meiosis-related genes, such as RAD51 and SMC2, were identified. We identified 38 miRNAs from DEGFu-sp to anther, and their targets were associated with pollen fertility and retrotransposon protein. Our study provides new germplasm for polyploid rice breeding, and revealed complex regulatory mechanisms that might be associated with heterosis and fertility.

Diabetic wounds are a worldwide health problem causing extremely heavy public health burden and require effective treatment. Optimal strategies for treating nonhealing diabetic wounds include stem-cell-based therapy and delivery of novel drug substances, such as functional microRNAs (miRNAs); however, miRNA easily degrades in the wound microenvironment. Herein, we developed a human adipose stem-cell-derived exosome (hASC-exos)-based miRNA delivery strategy to enhance its therapeutic efficacy. The miR-21-5p mimics, as novel therapeutic candidates for diabetic wounds, were loaded into hASC-exos by electroporation, taking advantage of natural availability and biocompatibility of exosomes as extracellular miRNA transporting particles. The engineered exosomes (E-exos) exhibited excellent effects on promoting proliferation and migration of keratinocytes via Wnt/β-catenin signaling in vitro and accelerating diabetic wound healing by increasing re-epithelialization, collagen remodeling, angiogenesis, and vessel maturation in vivo. Results from this study would set the fundamentals of applying hASC-exos to deliver future drug substances and to develop cell-free therapy for wound-healing treatments.

Metastatic peritoneal carcinoma (mPC) is a deadly disease without effective treatment. To improve treatment of this disease, a recently developed hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as the standard of care. However, the efficacy of this approach is limited by inefficient drug penetration and rapidly developed drug resistance. Herein, a nanotechnology approach is reported that is designed to improve drug delivery to mPC and to augment the efficacy of HIPEC through delivery of chemoimmunotherapy. First, the drug delivery efficiency of HIPEC is determined and it is found that chemotherapy agents cannot be efficiently delivered to large tumors nodules. To overcome the delivery hurdle, genetically engineered exosomes‐thermosensitive liposomes hybrid NPs, or gETL NPs, are then synthesized, and it is demonstrated that the NPs after intravenous administration efficiently penetrates into mPC tumors and releases payloads at the hypothermia condition of HIPEC. Last, it is shown that, when granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and docetaxel are co‐delivered, gETL NPs effectively inhibit tumor development and the efficacy is enhanced when HIPEC is co‐administered. The study provides a strategy to improve drug delivery to mPCs and offers a promising approach to improve treatment of the disease through combination of locoregional delivery of HIPEC and systemic delivery of chemoimmunotherapy via gETL NPs.

The oncogenic role of the long noncoding RNA associated with poor prognosis of hepatocellular carcinoma (lncRNA AWPPH) was reported in various types of malignancies; however, its involvement in ovarian carcinoma (OC) remains unknown. Thus, the present study investigated the role of AWPPH in OC. The expression of AWPPH in tissues and serum acquired from patients with OC, and healthy controls, was determined via reverse transcription-quantitative polymerase chain reaction. The diagnostic value of serum AWPPH expression was evaluated by receiver operating characteristic curve analysis. Additionally, survival curve analysis was performed to determine the prognostic value of AWPPH for OC. An AWPPH overexpression vector was transfected into OC cell lines. Cell proliferation, migration and invasion were analyzed via Cell Counting Kit-8, Transwell migration and invasion assays, respectively. The expression of β-catenin was investigated via western blotting. It was revealed that the expression levels of AWPPH were significantly upregulated in OC tissues and serum compared with healthy controls. The serum levels of AWPPH were able to effectively diagnose and predict the prognosis of patients with OC. AWPPH overexpression promoted the proliferation, migration and invasion of OC cells, and upregulated β-catenin expression. Treatment with a Wnt agonist markedly altered AWPPH expression; however, inhibition of Wnt suppressed the effects of AWPPH overexpression on proliferation, migration and invasion of OC cells. Therefore, it was revealed that AWPPH may promote OC via activation of the Wnt/β-catenin signaling pathway.

Epithelial-mesenchymal transition (EMT) has been shown to exert promoting effects on the progression of a number of cancer types, including endometrial carcinoma (EC). MicroRNA (miRNA or miR)-195 has been shown to function as a tumor suppressor. This study aimed to explore the potential role of miR-195 in the EMT process of EC. miR-195 overexpression (Mimics) and mimics control (Mock) vectors were constructed and transfected into human endometrial cancer cells (AN3-CA and Hec1A) using Lipofectamine 2000, and cell viability was detected using the Cell Counting kit-8 (CCK-8). The invasive and migratory capacities of the cells transfected with the Mimics or Mock vectors were assessed by Transwell and wound healing assays. Relative mRNA and protein levels were analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. Using TargetScan prediction, the potential target of miR-195 was identified and was further verified by dual-luciferase reporter assay. Following transfection with miR-195 mimics, the viability of the AN3-CA and Hec1A cells decreased in a time-dependent manner, specifically at 24 h. The wound closure rate and the number of invaded cells in the Mimics group were much lower than those in the Control and Mock groups (P<0.01). miR-195 overexpression significantly upregulated the mRNA and protein levels of tissue inhibitor of metalloproteinase 2 (TIMP-2), while it downregulated the expression levels of matrix metalloproteinase (MMP)-2 and MMP-9. Moreover, the phosphorylation levels of PI3K and AKT were also notably decreased (P<0.01). G protein-coupled estrogen receptor 1 (GPER) was identified as a target of miR-195. On the whole, the findings of this study indicate that the inhibitory effects of miR195 on EC cell migration and invasion are associated with the PI3K/AKT signaling pathway and GPER expression.

Bacterial vaginosis (BV) is a common type of vaginitis. Berberine is a natural alkaline product that reduces oxidative stress and apoptosis in cells. The aim of the present study was to investigate the effects of berberine on oxidative stress and apoptotic rates of BV. Vaginal epithelial and discharge samples were obtained from 60 healthy individuals and 180 patients with BV before and after one month of berberine treatment. Clinical observation was documented for all patients before and after treatment for comparison. Additionally, an in vitro study was performed; the samples were divided into groups the following groups: Control, model (H 2 O 2 -treated), LT (low-dose berberine), MT (medium-dose berberine) and HT (high-dose berberine). Expression levels of the oxidative stress related proteins were detected by western blotting. Clinical symptoms of patients with BV significantly improved following berberine treatment. Oxidative stress in vaginal discharge was significantly lower following treatment, indicated by the increased activity of superoxide dismutase (SOD) and catalase, as well as the reduced levels of malondialdehyde and H 2 O 2 . Apoptosis of the vaginal epithelial cells was also reduced, which was indicated by the reduced expression of apoptosis proteins caspase-3, cytochrome C, capase-12 and Bax, and increased expression of Bcl-2. The results of the in vitro experiments demonstrated a dose-dependent decrease in apoptosis with berberine treatment compared with levels before treatment. Oxidative stress relief was demonstrated by the reduced reactive oxygen species level and increased SOD and endothelial nitric oxide synthase levels, whereas suppression of apoptosis was further supported by the reduction in apoptotic proteins, as well as a decreased Bax/Bcl-2 ratio. Berberine exhibited effects on lowering oxidative stress in vaginal discharge and reducing oxidative damage, as well as apoptosis of the vaginal epithelium, which are beneficial to patients with bacterial vaginosis.

Pseudomonas aeruginosa is the most relevant pathogen to the severe exacerbations of patients with chronic obstructive pulmonary disease (COPD). However, the genetic and functional characteristics of P. aeruginosa isolates from COPD airways still remain less understood. In this study, the genetic, phylogenetic, phenotypic, and transcriptional features of P. aeruginosa isolates from COPD sputa were comprehensively explored by susceptibility testing, comparative-genomic analysis, phylogenetic analysis, phenotypic profiling, and comparative-transcriptomic analysis. We found that P. aeruginosa was prevalent in elder COPD patients and highly resisted to many commonly used antibiotics. P. aeruginosa COPD isolates harbored a substantial number of variant sites that might influence the primary metabolism and substance transport system. These isolates were discretely distributed in the phylogenetic tree and clustered with internationally collected P. aeruginosa in two major groups, and could be classified into three groups according to their differences in virulence-related phenotypes. Furthermore, the transcriptional patterns of COPD isolates could be classified into PAO1-like group with reduced protein secretion and motility and PAO1-distinct group with decreased substance transport but enhanced primary metabolism. In conclusion, this study demonstrates that P. aeruginosa isolates from COPD patients have abundant genetic and phenotypic diversity, and provides an important reference for further exploring the survival strategy of P. aeruginosa in COPD airways and the development of anti-pseudomonal therapy.

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