A Personalized Mobile Cessation Intervention to Promote Smokers From the Preparation Stage to the Action Stage: Double-blind Randomized Controlled Trial.

BACKGROUND: Most mobile cessation studies have found that such interventions have a higher quitting rate than interventions providing minimal smoking cessation support. However, why such interventions are effective has been almost unstudied by researchers. OBJECTIVE: This paper describes the principles of the personalized mobile cessation intervention-based WeChat app and used generalized estimated equations to assess why a personalized mobile cessation intervention was more likely to promote smokers from the preparation stage to the action stage than a nonpersonalized intervention. METHODS: This is a 2-arm, double-blind, randomized controlled trial in five cities in China. The intervention group received a personalized mobile cessation intervention. The control group received a nonpersonalized SMS text message smoking cessation intervention. All information was sent by the WeChat app. The outcomes were the change in protection motivation theory construct scores and the change in transtheoretical model stages. RESULTS: A total of 722 participants were randomly assigned to the intervention or control group. Compared with those who received the nonpersonalized SMS text message intervention, smokers who received the personalized intervention presented lower intrinsic rewards, extrinsic rewards, and response costs. Intrinsic rewards were determinants of stage change, thus explaining why the intervention group was more likely to promote smokers from the preparation stage to the action stage (odds ratio 2.65, 95% CI 1.41-4.98). CONCLUSIONS: This study identified the psychological determinants at different stages to facilitate smokers moving forward to the next stage of quitting behavior and provides a framework to explore why a smoking cessation intervention is effective. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100041942; https://tinyurl.com/2hhx4m7f.

Exosomal microRNA-139-5p from mesenchymal stem cells accelerates trophoblast cell invasion and migration by motivation of the ERK/MMP-2 pathway via downregulation of protein tyrosine phosphatase.

AIM: Exosomes present essential roles for intercellular interaction via extracellular pathways during systemic dysfunctions, including preeclampsia (PE). Here, we assessed the specific mechanism of mesenchymal stem cells (MSC)-originated exosomes in PE. METHODS: The effects of exosomes on trophoblasts were studied by EdU, wound healing, Transwell and TUNEL assays. By microarray analysis, we found that exosomes enhanced the microRNA-139-5p (miR-139-5p) in trophoblasts, and confirmed the target gene of miR-139-5p by bioinformatics prediction and dual-luciferase reporter gene assay. At the same time, ERK/MMP-2 pathway-related biomolecules were assessed through Western blot analysis. The pathway inhibitor was used for rescue experiments. Finally, the effect of exosomes on the pathology of PE rats was verified by in vivo experiments. RESULTS: The exosomes originated from hucMSC fostered the trophoblast cell migration, invasion and proliferation and obstructed apoptosis. Moreover, miR-139-5p could be transmitted to trophoblasts through hucMSC-secreted exosomes. miR-139-5p targeted protein tyrosine phosphatase (PTEN), which regulated the ERK/MMP-2 pathway. Inhibition of the ERK/MMP-2 pathway significantly reduced the promoting effect of exosomes on trophoblasts. Treatment with exosomes significantly lowered blood pressure values and reduced 24-h proteinuria in PE rats. CONCLUSION: hucMSC-originated exosomes overexpressing miR-139-5p activated the ERK/MMP-2 pathway via PTEN downregulation, thus accelerating trophoblast cell invasion and migration, and blocking apoptosis. These results demonstrated that hucMSC-derived exosomes overexpressing miR-139-5p might be an innovative direction for therapeutic approaches against PE.

Identification and analysis of long non-coding RNAs in response to H5N1 influenza viruses in duck (Anas platyrhynchos).

BACKGROUND: Long non-coding RNAs (lncRNAs) are important component of mammalian genomes, where their numbers are even larger than that of protein-coding genes. For example, human (Homo sapiens) (96,308 vs. 20,376) and mouse (Mus musculus) (87,774 vs. 22,630) have more lncRNA genes than protein-coding genes in the NONCODEv5 database. Recently, mammalian lncRNAs were reported to play critical roles in immune response to influenza A virus infections. Such observation inspired us to identify lncRNAs related to immune response to influenza A virus in duck, which is the most important natural host of influenza A viruses. RESULTS: We explored features of 62,447 lncRNAs from human, mouse, chicken, zebrafish and elegans, and developed a pipeline to identify lncRNAs using the identified features with transcriptomic data. We then collected 151,970 assembled transcripts from RNA-Seq data of 21 individuals from three tissues and annotated 4094 duck lncRNAs. Comparing to duck protein-coding transcripts, we found that 4094 lncRNAs had smaller number of exons (2.4 vs. 10.2) and longer length of transcripts (1903.0 bp vs. 1686.9 bp) on average. Among them, 3586 (87.6%) lncRNAs located in intergenic regions and 619 lncRNAs showed differential expression in ducks infected by H5N1 virus when compared to control individuals. 58 lncRNAs were involved into two co-expressional modules related to anti-influenza A virus immune response. Moreover, we confirmed that eight lncRNAs showed remarkably differential expression both in vivo (duck individuals) and in vitro (duck embryo fibroblast cells, DEF cells) after infected with H5N1 viruses, implying they might play important roles in response to influenza A virus infection. CONCLUSIONS: This study presented an example to annotate lncRNA in new species based on model species using transcriptome data. These data and analysis provide information for duck lncRNAs' function in immune response to influenza A virus.

Origin and development of oligoadenylate synthetase immune system.

BACKGROUND: Oligoadenylate synthetases (OASs) are widely distributed in Metazoa including sponges, fish, reptiles, birds and mammals and show large variation, with one to twelve members in any given species. Upon double-stranded RNA (dsRNA) binding, avian and mammalian OASs generate the second messenger 2'-5'-linked oligoadenylate (2-5A), which activates ribonuclease L (RNaseL) and blocks viral replication. However, how Metazoa shape their OAS repertoires to keep evolutionary balance to virus infection is largely unknown. We performed comprehensive phylogenetic and functional analyses of OAS genes from evolutionarily lower to higher Metazoa to demonstrate how the OAS repertoires have developed anti-viral activity and diversified their functions. RESULTS: Ancient Metazoa harbor OAS genes, but lack both upstream and downstream genes of the OAS-related pathways, indicating that ancient OASs are not interferon-induced genes involved in the innate immune system. Compared to OASs of ancient Metazoa (i.e. sponge), the corresponding ones of higher Metazoa present an increasing number of basic residues on the OAS/dsRNA interaction interface. Such an increase of basic residues might improve their binding affinity to dsRNA. Moreover, mutations of functional residues in the active pocket might lead to the fact that higher Metazoan OASs lose the ability to produce 3'-5'-linked oligoadenylate (3-5A) and turn into specific 2-5A synthetases. In addition, we found that multiple rounds of gene duplication and domain coupling events occurred in the OAS family and mutations at functionally critical sites were observed in most new OAS members. CONCLUSIONS: We propose a model for the expansion of OAS members and provide comprehensive evidence of subsequent neo-functionalization and sub-functionalization. Our observations lay the foundation for interrogating the evolutionary transition of ancient OAS genes to host defense genes and provide important information for exploring the unknown function of the OAS gene family.

High Expression of Ubiquitin-Specific Protease 8 (USP8) Is Associated with Poor Prognosis in Patients with Cervical Squamous Cell Carcinoma.

BACKGROUND Cervical cancer is one of the most common female malignancies in the world. The ubiquitin-specific protease 8 (USP8) functions by removing ubiquitin from protein substrates, and its potential role in cancer development was recently uncovered in lung cancer. The aim of this study was to investigate the expression and function of USP8 in cervical squamous cell carcinoma (CSCC). MATERIAL AND METHODS Immunohistochemical staining and quantitative PCR were performed to explore the expression of USP8 in both CSCC tissues and adjacent normal cervical tissues. Univariate and multivariate analyses were conducted to evaluate the clinical significance of USP8 in CSCC. Proliferation, migration, and invasion abilities of 2 CSCC cell lines were assessed after overexpression or silencing USP8, respectively. RESULTS Both the RNA and protein levels of USP8 were upregulated in CSCC tissues compared to normal cervical tissues. High expression of USP8 was correlated with advanced tumor stage and high recurrence risk. Moreover, USP8 was identified as a novel independent prognostic factor for CSCC patients. Cellular studies showed that USP8 can enhance the proliferation, migration, and invasion abilities of CSCC cells, thereby promoting tumor progression. CONCLUSIONS High expression of USP8 is frequent in CSCC tissues, which promotes tumor proliferation and invasion, and is correlated with a poor overall survival. Targeting USP8 may be a novel direction for drug development for CSCC therapy.

Functional evaluation of the insulin/insulin-like growth factor signaling pathway in determination of wing polyphenism in pea aphid.

Wing polyphenism is a common phenomenon that plays key roles in environmental adaptation of insects. Insulin/insulin-like growth factor signaling (IIS) pathway is a highly conserved pathway in regulation of metabolism, development, and growth in metazoans. It has been reported that IIS is required for switching of wing morph in brown planthopper via regulating the development of the wing pad. However, it remains elusive whether and how IIS pathway regulates transgenerational wing dimorphism in aphid. In this study, we found that pairing and solitary treatments can induce pea aphids to produce high and low percentage winged offspring, respectively. The expression level of ILP5 (insulin-like peptide 5) in maternal head was significantly higher upon solitary treatment in comparison with pairing, while silencing of ILP5 caused no obvious change in the winged offspring ratio. RNA interference-mediated knockdown of FoxO (Forkhead transcription factor subgroup O) in stage 20 embryos significantly increased the winged offspring ratio. The results of pharmacological and quantitative polymerase chain reaction experiments showed that the embryonic insulin receptors may not be involved in wing polyphenism. Additionally, ILP4 and ILP11 exhibited higher expression levels in 1st wingless offspring than in winged offspring. We demonstrate that FoxO negatively regulates the wing morph development in embryos. ILPs may regulate aphid wing polyphenism in a developmental stage-specific manner. However, the regulation may be not mediated by the canonical IIS pathway. The findings advance our understanding of IIS pathway in insect transgenerational wing polyphenism.