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Recent studies have revealed the significant role of the competing endogenous RNA (ceRNA) network in human diseases. However, systematic analysis of the ceRNA mechanism in chronic rhinosinusitis with nasal polyps (CRSwNP) is limited. In this study, we constructed a competitive endogenous RNA (ceRNA) network and identified a potential regulatory axis in CRSwNP based on bioinformatics analysis and experimental verification. We obtained lncRNA, miRNA, and mRNA expression profiles from the Gene Expression Omnibus. After analysis of CRSwNP patients and the control groups, we identified 565 DE-lncRNAs, 23 DE-miRNAs, and 1799 DE-mRNAs by the DESeq2 R package or limma R package. Enrichment analysis of 1799 DE-mRNAs showed that CRSwNP was associated with inflammation and immunity. Moreover, we identified 21 lncRNAs, 8 miRNAs and 8 mRNAs to construct the lncRNA-miRNA-mRNA ceRNA network. A potential MIAT/miR-125a/IRF4 axis was determined according to the degree and positive correlation between a lncRNA and its competitive endogenous mRNAs. The GSEA results suggested that IRF4 may be involved in immune cell infiltration. The validation of another dataset confirmed that MIAT and IRF4 were differentially expressed between the CRSwNP and control groups. The area under the ROC curve (AUC) of MIAT and IRF4 was 0.944. The CIBERSORT analysis revealed that eosinophils and M2 macrophages may be involved in the CRSwNP process. MIAT was correlated with dendritic cells and M2 macrophages, and IRF4 was correlated with dendritic cells. Finally, to validate the key genes, we performed in-silico validation using another dataset and experimental validation using immunohistochemistry, immunofluorescence, and Western blot. In summary, the constructed novel MIAT/miR-125a/IRF4 axis may play a critical role in the development and progression of CRSwNP. We believe that the ceRNA network and immune cell infiltration could offer further insight into novel molecular therapeutic targets for CRSwNP.

Spontaneous magnetic field generation plays important role in laser-plasma interactions. Strong quasi-static magnetic fields affect the thermal conductivity and the plasma dynamics, particularly in the case of ultra intense laser where the magnetic part of Lorentz force becomes as significant as the electric part. Kinetic simulations of giga-gauss magnetic field amplification via a laser irradiated microtube structure reveal the dynamics of charged particle implosions and the mechanism of magnetic field growth. A giga-gauss magnetic field is generated and amplified with the opposite polarity to the seed magnetic field. The spot size of the field is comparable to the laser wavelength, and the lifetime is hundreds of femtoseconds. An analytical model is presented to explain the underlying physics. This study should aid in designing future experiments.

Long non-coding RNA (lncRNA) is a transcription product of the mammalian genome that regulates the development and growth in the body. The present study aimed to analyze the expression dynamics of lncRNA in sika antler mesenchymal and cartilage tissues by high-throughput sequencing. Bioinformatics was applied to predict differentially expressed lncRNAs and target genes and screen lncRNAs and mRNAs related to osteogenic differentiation, cell proliferation, and migration. Finally, the expression of the lncRNAs and target genes were analyzed by qRT-PCR. The results showed that compared to the cartilage tissue, the transcription levels of lncRNA and mRNA, 1212 lncRNAs and 518 mRNAs, in mesenchymal tissue were altered significantly. Thus, a complex interaction network was constructed, and the lncRNA-mRNA interaction network correlation related to osteogenic differentiation, cell proliferation, and migration was analyzed. Among these, the 26 lncRNAs and potential target genes were verified by qRT-PCR, and the results of qRT-PCR were consistent with high-throughput sequencing results. These data indicated that lncRNA promotes the differentiation of deer antler mesenchymal tissue into cartilage tissue by regulating the related osteogenic factors, cell proliferation, and migration-related genes and accelerating the process of deer antler regeneration and development.

Hydroxyapatite (HA) is the main mineral constituent in the hard tissue of vertebrate, which is recognized as an important biomedical material owing to its excellent bioactivity and biocompatibility. Herein, we report a facile and green sonochemical route for the rapid synthesis of cellulose/HA nanocomposites in NaOH/urea aqueous solution. The in vitro behavior of the cellulose/HA nanocomposites was studied to evaluate the biological response of the nanocomposites following immersion in simulated body fluid for various periods (maximum of 28 days). The HA crystals formed on the surface of the nanocomposites were carbonate-containing apatite, which is similar to the naturally occurring calcium phosphate materials. The HA nanosheets (assembly of nanorods) were mineralized on the surface of the nanocomposites, and maximum mass of the nanocomposites was reached 1.82 times of initial mass after 28 days of soaking. Moreover, the as-prepared cellulose/HA nanocomposites have good cytocompatibility, and show a relatively high protein adsorption ability using hemoglobin as a model protein. These results indicate that the as-prepared cellulose/HA nanocomposites are promising for applications in various biomedical fields such as tissue engineering and protein/drug delivery.

Dynamic mitigation for the tearing mode instability in the current sheet in collisionless plasmas is demonstrated by applying a wobbling electron current beam. The initial small amplitude modulations imposed on the current sheet induce the electric current filamentation and the reconnection of the magnetic field lines. When the wobbling or oscillatory motion is added from the electron beam having a form of a thin layer moving along the current sheet, the perturbation phase is mixed and consequently the instability growth is saturated remarkably, like in the case of the feed-forward control.

Minimizing pain and maximizing pleasure are conflicting motivations when pain and reward co-occur. Decisions to prioritize reward consumption or pain avoidance are assumed to lead to pain inhibition or facilitation, respectively. Such decisions are a function of the subjective utility of the stimuli involved, i.e. the relative value assigned to the stimuli to compare the potential outcomes of a decision. To test perceptual pain modulation by varying degrees of motivational conflicts and the role of subjective utility, we implemented a task in which healthy volunteers had to decide between accepting a reward at the cost of receiving a nociceptive electrocutaneous stimulus or rejecting both. Subjective utility of the stimuli was assessed by a matching task between the stimuli. Accepting reward coupled to a nociceptive stimulus resulted in decreased perceived intensity, while rejecting the reward to avoid pain resulted in increased perceived intensity, but in both cases only if a high motivational conflict was present. Subjective utility of the stimuli involved moderated these bidirectional perceptual effects: the more a person valued money over pain, the more perceived intensity increased or decreased. These findings demonstrate pain modulation when pain and reward are simultaneously present and highlight the importance of subjective utility for such modulation.

High tumor vascular endothelial growth factor (VEGF) levels are associated with poor treatment outcomes in prostate cancer (PCa), and immune deficiency in the PCa microenvironment, especially suppression of dendritic cell (DC) proliferation, has been confirmed. In this study, we (1) investigated whether VEGF participates in DC suppression in murine PCa cells (RM-1), (2) down-regulated VEGF expression using low-frequency ultrasound and microbubbles (UM), and (3) further explored any synergistic effect on immunological activation. DCs from the bone marrow of BALB/c mice were stimulated by the addition of cytokines (granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4)), and we analyzed their proliferation status via flow cytometric recognition of the surface antigen markers CD11c and CD83. The results demonstrated that co-culture with RM-1 cells markedly inhibited expression of the general marker CD11c and the mature marker CD83; UM weakened this inhibition by down-regulating VEGF expression. T lymphocytes were extracted from murine spleens, and CD4 and CD8a were identified as the biomarkers of activated cells participating in the anti-tumor immune response. When DCs, T lymphocytes and RM-1 cells were co-cultured, cell migration and invasion assays and cytoactive detection showed that UM could not only directly suppress PCa cell evolution but also promote activation of anti-tumor immunocytes in the VEGF-inhibited microenvironment.

Shikonin and its derivatives extracted from Lithospermeae plants’ red roots have current applications in food and pharmaceutical industries. Previous studies have cloned some genes related to shikonin biosynthesis. However, most genes related to shikonin biosynthesis remain unclear, because the lack of the genome/transcriptome of the Lithospermeae plants. Therefore, in order to provide a new understanding of shikonin biosynthesis, we obtained transcriptome data and unigenes expression profiles in three shikonin-producing Lithospermeae plants, i.e., Lithospermum erythrorhizon, Arnebia euchroma and Echium plantagineum. As a result, two unigenes (i.e., G10H and 12OPR) that are involved in “shikonin downstream biosynthesis” and “methyl jasmonate biosynthesis” were deemed to relate to shikonin biosynthesis in this study. Furthermore, we conducted a Lamiids phylogenetic model and identified orthologous unigenes under positive selection in above three Lithospermeae plants. The results indicated Boraginales was more relative to Solanales/Gentianales than to Lamiales.

We investigate the transport problem that a spinful matter wave is incident on a strong localized spin-orbit-coupled Bose-Einstein condensate in optical lattices, where the localization is admitted by atom interaction only existing at one particular site, and the spin-orbit coupling arouse spatial rotation of the spin texture. We find that tuning the spin orientation of the localized Bose-Einstein condensate can lead to spin-nonreciprocal/spin-reciprocal transport, meaning the transport properties are dependent on/independent of the spin orientation of incident waves. In the former case, we obtain the conditions to achieve transparency, beam-splitting, and blockade of the incident wave with a given spin orientation, and furthermore the ones to perfectly isolate incident waves of different spin orientation, while in the latter, we obtain the condition to maximize the conversion of different spin states. The result may be useful to develop a novel spinful matter wave valve that integrates spin switcher, beam-splitter, isolator, and converter. The method can also be applied to other real systems, e.g., realizing perfect isolation of spin states in magnetism, which is otherwise rather difficult.

Signal transducer and activator of transcription 3 (STAT3) is hyper-activated in diversiform human tumors and has been validated as an attractive therapeutic target. Current research showed that a natural product, shikonin, along with its synthetic analogues, is able to inhibit the activity of STAT3 potently. The potential space of shikonin in developing novel anti-cancer agents encouraged us to carry out the investigation of the probable binding mode with STAT3. From this foundation, we have designed new types of STAT3 SH2 inhibitors. Combined simulations were performed to filter for the lead compound, which was then substituted, synthesized and evaluated by a variety of bioassays. Among the entities, PMM-172 exhibited the best anti-proliferative activity against MDA-MB-231 cells with IC50 value 1.98 ± 0.49 μM. Besides, it was identified to decrease luciferase activity, induce cell apoptosis and reduce mitochondrial transmembrane potential in MDA-MB-231 cells. Also, PMM-172 inhibited constitutive/inducible STAT3 activation without affecting STAT1 and STAT5 in MDA-MB-231 cells, and had no effect in non-tumorigenic MCF-10A cells. Moreover, PMM-172 suppressed STAT3 nuclear localization and STAT3 downstream target genes expression. Overall, these results indicate that the antitumor activity of PMM-172 is at least partially due to inhibition of STAT3 in breast cancer cells.

Mitochondria have a central position in innate immune response via the adaptor protein MAVS in mitochondrial outer membrane to limit viral replication by inducing interferon production. Here, we reported that C11orf83, a component of complex III of electronic transfer chain in mitochondrial inner membrane, was a potent antiviral protein independent of interferon production. C11orf83 expression significantly increased in response to viral infection, and endows cells with stronger capability of inhibiting viral replication. Deletion of C11orf83 permits viral replication easier and cells were more vulnerable to viral killing. These effects mainly were mediated by triggering OAS3-RNase L system. C11orf83 overexpression induced higher transcription of OAS3, and knockdown either OAS3 or RNase L impaired the antiviral capability of C11orf83. Interestingly, the signaling from C11orf83 to OAS3-RNase L was independent of interferon production. Thus, our findings suggested a new antiviral mechanism by bridging cell metabolic machinery component with antiviral effectors.

We report on the optical and structural characterization of rubrene polycrystalline films fabricated from vacuum deposition with various substrate temperatures (Tsub). Depending on Tsub, the role of twisted and planar rubrene conformational isomers on the properties of rubrene films is focused. The temperature (T)-dependent inverse optical transmission (IOT) and photoluminescence (PL) spectra were performed on these rubrene films. The origins of these IOT and PL peaks are explained in terms of the features from twisted and planar rubrene molecules and of the band characteristics from rubrene molecular solid films. Here, two rarely reported weak-peaks at 2.431 and 2.605 eV were observed from IOT spectra, which are associated with planar rubrene. Besides, the T-dependence of optical bandgap deduced from IOT spectra is discussed with respect to Tsub. Together with IOT and PL spectra, for Tsub > 170 °C, the changes in surface morphology and unit cell volume were observed for the first time, and are attributed to the isomeric transformation from twisted to planar rubrenes during the deposition processes. Furthermore, a unified schematic diagram in terms of Frenkel exciton recombination is suggested to explain the origins of the dominant PL peaks performed on these rubrene films at 15 K.

The effects of Bone morphogenetic protein 2 (BMP-2) on the angiogenesis of hepatocellular carcinoma have not yet been observed and its molecular mechanisms is not clear. We first constructed the recombinant lentivirus vectors expressing small hairpin RNA against BMP-2 gene (LV-SH-BMP2) and the recombinant lentivirus vectors over-expressing BMP-2 (overexpression-LV-BMP2), and then the two recombinant lentivirus vectors were respectively transfected into Hep G2 cells. The Hep G2 cells transfected with LV-SH-BMP2 or overexpression-LV-BMP2 were respectively co-cultured with human umbilical vein endothelial cells (HUVECs) to observe the effects of BMP-2 on HUVECs. The effect of BMP-2 on tumor microvessel density (MVD) was examined. The abilities of proliferation, migration and angiogenesis were significantly inhibited in the HUVECs co-cultured with BMP-2 knockdown Hep G2 (all P P P

Porcine epidemic diarrhea virus (PEDV) is a highly contagious coronavirus that causes severe diarrhea and death, particularly in neonatal piglets. The nucleocapsid protein (N protein) of PEDV presents strong immunogenicity and contributes to the cross-reactivity between PEDV and TGEV. However, the characterization of epitopes on the PEDV N protein remains largely unknown. Here, two monoclonal antibodies (MAbs) specific to the N protein of a PEDV strain, FJzz1/2011, were generated and screened against a partially overlapping library of 24 GST-fusion N protein-truncated constructs. We confirmed that residues 18–133 (designated NEP-D4) and residues 252–262 (designated NEP-D6) were the epitopes targeted by MAbs PN-D4 and PN-D6, respectively. Sequence analysis revealed that these two epitopes were highly conserved among PEDV strains but were significantly different from other members of the Coronavirinae subfamily. Western blot analysis showed that they could be specifically recognized by PEDV antisera but could not be recognized by TGEV hyperimmune antisera. Indirect immunofluorescence (IFA) assays confirmed no cross-reaction between these two MAbs and TGEV. In addition, the freeze-thaw cycle and protease treatment results indicated that NEP-D4 was intrinsically disordered. All these results suggest that these two novel epitopes and their cognate MAbs could serve as the basis for the development of precise diagnostic assays for PEDV.

SAMHD1 is a type I interferon (IFN) inducible host innate immunity restriction factor that inhibits an early step of the viral life cycle. The underlying mechanisms of SAMHD1 transcriptional regulation remains elusive. Here, we report that inducing SAMHD1 upregulation is part of an early intrinsic immune response via TLR3 and RIG-I/MDA5 agonists that ultimately induce the nuclear translocation of the interferon regulation factor 3 (IRF3) protein. Further studies show that IRF3 plays a major role in upregulating endogenous SAMHD1 expression in a mechanism that is independent of the classical IFN-induced JAK-STAT pathway. Both overexpression and activation of IRF3 enhanced the SAMHD1 promoter luciferase activity, and activated IRF3 was necessary for upregulating SAMHD1 expression in a type I IFN cascade. We also show that the SAMHD1 promoter is a direct target of IRF3 and an IRF3 binding site is sufficient to render this promoter responsive to stimulation. Collectively, these findings indicate that upregulation of endogenous SAMHD1 expression is attributed to the phosphorylation and nuclear translocation of IRF3 and we suggest that type I IFN induction and induced SAMHD1 expression are coordinated.

Overexpression of folate receptor alpha (FRα) and high telomerase activity are considered to be the characteristics of ovarian cancers. In this study, we developed FRα-targeted lipoplexes loaded with an hTERT promoter-regulated plasmid that encodes a matrix protein (MP) of the vesicular stomatitis virus, F-LP/pMP(2.5), for application in ovarian cancer treatment. We first characterized the pharmaceutical properties of F-LP/pMP(2.5). The efficient expression of the MP-driven hTERT promoter in SKOV-3 cells was determined after an in-vitro transfection assay, which was significantly increased compared with a non-modified LP/pMP(2.5) group. F-LP/pMP(2.5) treatment significantly inhibited the growth of tumors and extended the survival of mice in a SKOV-3 tumor model compared with other groups. Such an anti-tumor effect was due to the increased expression of MP in tumor tissue, which led to the induction of tumor cell apoptosis, inhibition of tumor cell proliferation and suppression of tumor angiogenesis. Furthermore, a preliminary safety evaluation demonstrated a good safety profile of F-LP/pMP(2.5) as a gene therapy agent. Therefore, FRα-targeted lipoplexes with therapeutic gene expression regulated by an hTERT promoter might be a promising gene therapy agent and a potential translational candidate for the clinical treatment of ovarian cancer.

It has been shown that there are not only transverse but also longitudinal couplings between microwave fields and a superconducting qubit with broken inversion symmetry of the potential energy. Using multiphoton processes induced by longitudinal coupling fields and frequency matching conditions, we design a universal algorithm to produce arbitrary superpositions of two-mode photon states of microwave fields in two separated transmission line resonators, which are coupled to a superconducting qubit. Based on our algorithm, we analyze the generation of evenly-populated states and NOON states. Compared to other proposals with only single-photon process, we provide an efficient way to produce entangled microwave photon states when the interactions between superconducting qubits and microwave fields are in the strong and ultrastrong regime.

Obesity was shown to cause reproductive dysfunctions such as reduced conception, infertility and early pregnancy loss. However, the possible effects of obesity on oocyte quality are still not fully understood. In this study we investigated the effects of both diet and gene mutation induced obesity on impairments in mouse oocyte polarization, oxidative stress and epigenetic modifications. Our results showed that high-fat diet induced obesity (HFD) and gene mutation induced obesity (ob/ob) could both impair oocyte meiotic maturation, disrupt spindle morphology and reduce oocyte polarity. Oocytes from obese mice underwent oxidative stress, as shown by high DHE and ROS levels. Abnormal mitochondrial distributions and structures were observed in oocytes from obese groups of mice and early apoptosis signals were detected, which suggesting that oxidative stress had impaired mitochondrial function and resulted in oocyte apoptosis. Our results also showed that 5 mC levels and H3K9 and H3K27 methylation levels were altered in oocytes from obese mice, which indicated that DNA methylation and histone methylation had been affected. Our results showed that both HFD and ob/ob induced obesity affected oocyte maturation and that oxidative stress-induced early apoptosis and altered epigenetic modifications may be the reasons for reduced oocyte quality in obese mice.