Emerging evidence suggests that microRNA (miRNA) and long noncoding RNA (lncRNA) play important roles in disease development. However, the mechanism underlying mRNA interaction with miRNA and lncRNA in idiopathic pulmonary fibrosis (IPF) remains unknown. This study presents a novel lnc-PCF that promotes the proliferation of TGF-β1-activated epithelial cells through the regulation of map3k11 by directly targeting miR-344a-5p during pulmonary fibrogenesis. Bioinformatics and in vitro translation assay were performed to confirm whether or not lnc-PCF is an actual lncRNA. RNA fluorescent in situ hybridization (FISH) and nucleocytoplasmic separation showed that lnc-PCF is mainly expressed in the cytoplasm. Knockdown and knockin of lnc-PCF indicated that lnc-PCF could promote fibrogenesis by regulating the proliferation of epithelial cells activated by TGF-β1 according to the results of xCELLigence real-time cell analysis system, flow cytometry, and western blot analysis. Computational analysis and a dual-luciferase reporter system were used to identify the target gene of miR-344a-5p, whereas RNA pull down, anti-AGO2 RNA immunoprecipitation, and rescue experiments were conducted to confirm the identity of this direct target. Further experiments verified that lnc-PCF promotes the proliferation of activated epithelial cells that were dependent on miR-344a-5p, which exerted its regulatory functions through its target gene map3k11. Finally, adenovirus packaging sh-lnc-PCF was sprayed into rat lung tissues to evaluate the therapeutic effect of lnc-PCF. These findings revealed that lnc-PCF can accelerate pulmonary fibrogenesis by directly targeting miR-344a-5p to regulate map3k11, which may be a potential therapeutic target in IPF.

Ecosystem models are valuable tools for informing fisheries management due to their ability to simulate the spatial dynamics of modelled species, their trophic interactions, and their responses to fishing in an ecosystem context. In this study, we developed an OSMOSE (Object-oriented Simulator of Marine Ecosystems Exploitation) model for the Pacific North Coast Integrated Management Area (PNCIMA) ecosystem off western Canada, which simulated the entire life cycle of six key species and for the first time integrated spatial population structure and “background” taxa. Background taxa are of secondary importance for the study at hand but have the potential to be important prey or predators of the key species. The primary aim of the study was to explore how the population dynamics of the key species differed over time and different management areas, with results focusing on Pacific Herring (Clupea pallasii) and Pacific Cod (Gadus macrocephalus) that have been assessed on a single-species basis in the last 5 years. Results found that the population dynamics of a specific species varied in different management areas due to differences in species interactions particularly in the form of predation mortality, which supports the current area-specific assessment and management framework. The study also indicated that increasing predation mortality may have caused the decline of the Pacific Cod populations. By contrast, increasing starvation mortality was found to be a limiting factor for the Pacific Herring populations. The discoveries from these OSMOSE simulations provide important information for fisheries management within the PNCIMA ecosystem.

BackgroundAging is a known risk factor of idiopathic pulmonary fibrosis (IPF). However, the pathogenic mechanisms underlying the effects of advanced aging remain largely unknown. Telomeric repeat-containing RNA (TERRA) represents a type of long noncoding RNA. In this study, the regulatory roles of TERRA on human telomeres and mitochondria and IPF epithelial injury model were identified.MethodsBlood samples were collected from patients with IPF (n = 24) and matched control individuals (n = 24). The significance of clinical research on the TERRA expression correlated with pulmonary fibrosis was assessed. The expression levels of TERRA in vivo and in vitro were determined through quantitative real-time polymerase chain reaction analysis. Telomerase activity was observed using a fluorescent quantitative TRAP assay kit. The functions of telomeres, mitochondria, and associated genes were analyzed through RNA interference on TERRA.ResultsTERRA expression levels significantly increased in the peripheral blood mononuclear cells of IPF patients. The expression levels also exhibited a direct and significantly inverse correlation with the percentage of predicted force vital capacity, which is a physiological indicator of fibrogenesis during IPF progression. This finding was confirmed in the epithelial injury model of IPF in vitro. RNA interference on TERRA expression can ameliorate the functions of telomeres; mitochondria; associated genes; components associated with telomeres, such as telomerase reverse transcriptase, telomerase, and cell nuclear antigen, cyclin D1; and mitochondria-associated cyclin E genes, including the MMP and Bcl-2 family. The RNA interference on TERRA expression can also improve the functions of oxidative-stress-associated genes, such as reactive oxygen species, superoxide dismutase, and catalase, and apoptosis-related genes, such as cytochrome c, caspase-9, and caspase-3.ConclusionsIn this study, the regulation of TERRA expression on telomeres and mitochondria during IPF pathogenesis was identified for the first time. The results may provide valuable insights for the discovery of a novel biomarker or therapeutic approach for IPF treatment.

We previously demonstrated that for long-term spastic limb paralysis, transferring the seventh cervical nerve (C7) from the nonparalyzed side to the paralyzed side results in increase of 17.7 in Fugl-Meyer score. One strategy for further improvement in voluntary arm movement is selective activation of five target muscles innervated by C7 during recovery process. In this study, we develop an implantable multisite optogenetic stimulation device (MOSD) based on shape-memory polymer. Two-site stimulation of sciatic nerve bundles by MOSD induces precise extension or flexion movements of the ankle joint, while eight-site stimulation of C7 nerve bundles induce selective limb movement. Long-term implant of MOSD to mice with severed and anastomosed C7 nerve is proven to be both safe and effective. Our work opens up the possibility for multisite nerve bundle stimulation to induce highly-selective activations of limb muscles, which could inspire further applications in neurosurgery and neuroscience research.

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Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in idiopathic pulmonary fibrosis (IPF) regulation is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 is yet to be investigated. Additionally, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual-luciferase reporter assay system were used to identify the target gene of miR-30a, and cell transfection was utilized to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and miR-30a mimic and inhibitor transfection significantly reduced and increased the TET1 protein expression, respectively. Further experimentation verified that the TET1 siRNA interference could inhibit Drp-1 promoter hydroxymethylation. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit TET1 expression through base pairing with complementary sites in the 3 untranslated region to regulate Drp-1 promoter hydroxymethylation. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), play increasingly important roles in pathological processes involved in disease development. However, whether mRNAs interact with miRNAs and lncRNAs to form an interacting regulatory network in diseases remains unknown. In this study, the interaction of coexpressed mRNAs, miRNAs and lncRNAs during tumor growth factor-β1-activated (TGF-β1) epithelial-mesenchymal transition (EMT) was systematically analyzed in human alveolar epithelial cells. For EMT regulation, 24 mRNAs, 11 miRNAs and 33 lncRNAs were coexpressed, and interacted with one another. The interaction among coexpressed mRNAs, miRNAs and lncRNAs were further analyzed, and the results showed the lack of competing endogenous RNAs (ceRNAs) among them. The mutual regulation may be correlated with other modes, such as histone modification and transcription factor recruitment. However, the possibility of ceRNA existence cannot be ignored because of the generally low abundance of lncRNAs and frequent promiscuity of protein-RNA interactions. Thus, conclusions need further experimental identification and validation. In this context, disrupting many altered disease pathways remains one of the challenges in obtaining effective pathway-based therapy. The reason being that one specific mRNA, miRNA or lncRNA may target multiple genes that are potentially implicated in a disease. Nevertheless, the results of the present study provide basic mechanistic information, possible biomarkers and novel treatment strategies for diseases, particularly pulmonary tumor and fibrosis.

The marine ecosystem off British Columbia (BC), Canada, has experienced various changes in the last two decades, including reduced lipid-rich zooplankton biomass, increased marine mammals, and deteriorated commercial fisheries, particularly those targeting pelagic species such as Pacific Herring (Clupea pallasii). Understanding how stressors interactively and cumulatively affect commercially important fish species is key to moving toward ecosystem-based fisheries management. Because it is challenging to assess the cumulative effects of multiple stressors by using empirical data alone, a dynamic, individual-based spatially explicit ecosystem modeling platform such as Object-oriented Simulator of Marine Ecosystems (OSMOSE) represents a valuable tool to simulate ecological processes and comprehensively evaluate how stressors cumulatively impact modeled species. In this study, we employed OSMOSE to investigate the cumulative effects of fishing, plankton biomass change, and marine mammal consumption on the dynamics of some fish species and the BC marine ecosystem as a whole. We specifically simulated ecosystem dynamics during the last 20 years under two sets of scenarios: (1) unfavorable conditions from the perspective of commercial fish species (i.e., doubling fishing mortality rates, halving plankton biomass, and doubling marine mammal biomass, acting individually or collectively); and (2) favorable conditions with the three factors having opposite changes (i.e., halving fishing mortality rates, doubling plankton biomass, and halving marine mammal biomass, acting individually or collectively). Our results indicate that, under unfavorable conditions, the degree to which species biomass was reduced varied among species, and that negative synergistic and negative dampened effects were dominant under historical and doubled fishing mortality rates, respectively. Under favorable conditions, species biomasses did not increase as much as expected due to the existence of complex predator-prey interactions among fish species, and positive synergistic and positive dampened effects were prevailing under historical and halved fishing mortality rates, respectively. The