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An analytical model for the dynamic response of a defective periodic viaduct (DPV) (i.e. an infinite periodic viaduct containing a defective span) to harmonic seismic waves is proposed. In the proposed model, the viaduct is divided into three parts – left and right semi-infinite ordered periodic viaducts (SOPVs) and the defective span. The total responses of the left and right SOPVs consist of two parts – a free part and a scattered part. The free-part responses are associated with the forced vibration of the corresponding SOPVs due to seismic waves, while the scattered-part responses are relevant to the scattered characteristic waves of the ordered periodic viaduct (OPV) in the SOPVs. The amplitudes of the scattered characteristic waves in the left and right SOPVs can be determined by using the transfer matrix of the defective span. The numerical results suggest that when a DPV is subjected to harmonic seismic waves, a resonance-type response will occur. It was also found that, for the DPV, there are two kinds of resonance frequencies: the frequencies associated with the corresponding OPV and additional frequencies due to the presence of the defective span.

CXC chemokine receptor 4 (CXCR4), a member of the G-protein-coupled receptor family, plays an important role in host immune responses. Within the teleost lineage, there are two paralogs of CXCR4; however, the role of CXCR4 in teleost B cells is poorly understood. In this study, we determined the cDNA sequences of the two CXCR4 paralogs from the Japanese sea bass (Lateolabrax japonica; LjCXCR4a and LjCXCR4b). Sequence and phylogenetic tree analyses revealed that LjCXCR4a and LjCXCR4b are most closely related to CXCR4a and CXCR4b, respectively, in the large yellow croaker (Larimichthys crocea). CXCR4 transcripts were mainly expressed in the gills, and their expression in different tissues was altered upon infection with Vibrio harveyi. LjCXCR4a and LjCXCR4b protein levels were upregulated in infected B cells. Knockdown of LjCXCR4a and LjCXCR4b in B cells by RNA interference, the phagocytic activity of B cells was not affected. Furthermore, knockdown of LjCXCR4a, not of LjCXCR4b, was observed to inhibit LjIgM expression in lipopolysaccharide-stimulated B cells. In addition, knockdown of LjCXCR4a, not of LjCXCR4b, was found to reduce reactive oxygen species levels in B cells. Our results indicate that LjCXCR4a and LjCXCR4b modulate the immune response of Japanese sea bass B cells against bacterial infection, albeit via different pathways.

Large underground caverns are characterized by high geostress, high sidewalls and complex geological conditions, which make the rock masses suffer a series of failures in the process of excavation. The excavation of the large underground powerhouse of the Baihetan Hydropower Station in China is based on the drilling and blasting method with small steps and weak-vibration blasting. To thoroughly understand the mechanism of blasting excavation on the surrounding rock, in situ microseismic (MS) monitoring system was established to analyze the blast-induced microseismicity of the large underground powerhouse of the Baihetan Hydropower Station. The waveform characteristics of blasting events and rock fracturing events are distinguished first. Then, the spatial distribution of density contours of MS events and rock mass seismic deformation induced by blasting excavation are obtained. The results show that the blast-induced risk areas are mainly concentrated in the downstream sidewall of the underground powerhouse. MS monitoring in real time during the excavation process can provide data reference for the dynamic optimization of on-site construction schemes.

Atopic dermatitis is a common chronic pruritic inflammatory disease of the skin involving neuro-immune communication. Neuronal mechanism-based therapeutic treatments remain lacking. We investigated the efficacy of intravenous lidocaine therapy on atopic dermatitis and the underlying neuro-immune mechanism.Pharmacological intervention, immunofluorescence, RNA-sequencing, genetic modification and immunoassay were performed to dissect the neuro-immune basis of itch and inflammation in atopic dermatitis-like mouse model and in patients.Lidocaine alleviated skin lesions and itch in both atopic dermatitis patients and calcipotriol (MC903)-induced atopic dermatitis model by blocking subpopulation of sensory neurons. QX-314, a charged NaNa

Transcription factor PU.1 is a regulator of macrophage function, however, the specific function of PU.1 in teleost monocytes/macrophages (MO/MФ) remains unknown. We determined the cDNA sequence of two PU.1 genes from ayu (Plecoglossus altivelis; PaPU.1a and PaPU.1b). Sequence comparisons showed that PaPU.1 were most closely related to the PU.1 of rainbow smelt (Osmerus mordax). The PU.1 transcripts were mainly expressed in the spleen, and their expression was altered in various tissues upon infection with Vibrio anguillarum. PaPU.1a and PaPU.1b proteins were upregulated in MO/MФ, after infection. RNA interference was employed to knockdown PaPU.1a and PaPU.1b to investigate their function in MO/MФ. The expression of inflammatory cytokines was regulated by PaPU.1a, but not PaPU.1b, in ayu MO/MФ upon V. anguillarum infection. Both PaPU.1a and PaPU.1b knockdown lowered the phagocytic activity of MO/MФ. Furthermore, PaPU.1b knockdown attenuated MO/MФ bacterial killing capability. Our results indicate that two PaPU.1 genes differentially modulate the immune response in ayu MO/MФ against bacterial infection.

Chronic pollution in aquatic ecosystems can lead to many adverse effects, including a greater susceptibility to pathogens among resident biota. Trifloxystrobin (TFS) is a strobilurin fungicide widely used in Asia to control soybean rust. However, it has the potential to enter aquatic ecosystems, where it may impair fish resistance to viral infections. To explore the potential environmental risks of TFS, we characterized the antiviral capacities of fish chronically exposed to TFS and subsequently infected with spring viraemia of carp virus (SVCV). Although TFS exhibited no significant cytotoxicity at the tested environmental concentrations during viral challenge, SVCV replication increased significantly in a time-dependent manner within epithelioma papulosum cyprini (EPC) cells and zebrafish exposed to 25 μg/L TFS. Results showed that the highest viral load was more than 100-fold that of the controls. Intracellular biochemical assays indicated that autophagy was induced by TFS, and associated changes included an increase in autophagosomes, conversion of LC3-II, accumulation of Beclin-1, and degradation of P62 in EPC cells and zebrafish. In addition, TFS markedly decreased the expression and phosphorylation of mTOR, indicating that activation of TFS may be associated with the mTOR-mediated autophagy pathway. This study provides new insights into the mechanism of the immunosuppressive effects of TFS on non-target aquatic hosts and suggests that the existence of TFS in aquatic environments may contribute to outbreaks of viral diseases.水生生态系统中存在的长期污染会对水生环境以及水生生物产生多种不利影响，其中包括提高水生生物对病原体的敏感性。肟菌酯（TFS）是一种在亚洲广泛用于防治大豆锈病的甲氧基丙烯酸酯类农药。然而，在长期使用的过程中它有可能进入并污染水生生态系统导致鱼类对病毒抵抗力降低。为了研究TFS潜在的水环境风险，我们检测了长期暴露于TFS的宿主在鲤春病毒血症病毒（spring viraemia of carp virus，SVCV）感染下抗病能力的变化。实验结果表明，尽管环境浓度25 μg/L暴露下的TFS对细胞和斑马鱼没有明显毒性，但SVCV增殖却随着暴露时间的增长显著增加，最高病毒载量甚至相对于对照组呈现100倍以上的增加。先前的研究表明，鱼类出现自噬将有利于SVCV在机体内增殖。而我们则发现，长时间TFS暴露下的EPC细胞和斑马鱼出现自噬体增加、LC3蛋白转化、Beclin-1累积、P62蛋白降解及mTOR表达和磷酸化水平下降，这些说明TFS通过诱导宿主自噬提高宿主的病毒易感性。综上所述，该研究提出了TFS对非靶标水生生物致毒机制的新见解，提醒我们应关注甲氧基类农药在水环境中蓄积可能会诱发鱼类病毒病暴发，从而危及生态环境的安全。.

Peptidoglycan recognition proteins (PGRPs) belong to a member of pattern-recognition receptors (PRRs), which proposed as antibacterial protein. The present study investigated the antibacterial effect of BpPGRP5 in great blue-spotted mudskipper (Boleophthalmus pectinirostris). BpPGRP5 transcript was detected in all tested tissues with the highest expression level in spleen, and its expression was significantly upregulated in spleen, intestine, and kidney following Aeromonas veronii infection. rBpPGRP5 was found to interact with several polysaccharides and bacteria, including Gram-negative bacteria (Escherichia coli and A. veronii) and Gram-positive bacteria (Listeria monocytogenes and Staphylococcus aureus). rBpPGRP5 inhibited the proliferation of E. coli, S. aureus, L. monocytogenes, and A. veronii in a Zn

In this paper, the dynamic response of an infinite periodic viaduct (IPV) subjected to an moving mass and harmonic seismic waves simultaneously is studied using Fourier transform method and finite element method (FEM). According to the periodicity of the IPV, the mass–viaduct contact force (MVCF) is expanded into Fourier series, each of which represents a moving load component of the MVCF. The response of the IPV to the moving load component can be obtained by using the response of the IPV to a frequency-wavenumber domain unit load determined by the FEM. The response of the IPV to harmonic seismic waves can also be determined via the FEM. With the obtained responses of the IPV to the moving load component and seismic waves as well as the equation of the motion for the moving mass, the coupling equation between the moving mass and the IPV is derived, with which the Fourier coefficients of the MVCF can be evaluated. Superposition of the response of the IPV to the moving load components and that to seismic waves yields the total response of the IPV to the moving mass and seismic waves. The presented numerical results indicate that for the simplified IPV model used in this study, the in-plane transverse displacement of the beam of the IPV due to the joint action of the moving mass and seismic wave is larger than that due to the seismic wave alone, while for the out-of-plane vibration, the transverse displacement of the beam of the IPV due to the moving mass and seismic wave together is usually smaller than that due to the seismic wave only.

Rapid and user-friendly diagnostic tests are necessary for early diagnosis and immediate detection of diseases, particularly for on-site screening of pathogenic microorganisms in aquaculture. In this study, we developed a dual-sample microfluidic chip integrated with a real-time fluorogenic loop-mediated isothermal amplification assay (dual-sample on-chip LAMP) to simultaneously detect 10 pathogenic microorganisms, that is Aeromonas hydrophila, Edwardsiella tarda, Vibrio harveyi, V. alginolyticus, V. anguillarum, V. parahaemolyticus, V. vulnificus, infectious hypodermal and haematopoietic necrosis virus, infectious spleen and kidney necrosis virus, and white spot syndrome virus. This on-chip LAMP provided a nearly automated protocol that can analyse two samples simultaneously, and the tests achieved limits of detection (LOD) ranging from 100 to 10-1 pg/μl for genomic DNA of tested bacteria and 10-4 to 10-5 pg/μl for recombinant plasmid DNA of tested viruses, with run times averaging less than 30 min. The coefficient of variation for the time-to-positive value was less than 10%, reflecting a robust reproducibility. The clinical sensitivity and specificity were 93.52% and 85.53%, respectively, compared to conventional microbiological or clinical methods. The on-chip LAMP assay provides an effective dual-sample and multiple pathogen analysis, and thus would be applicable to on-site detection and routine monitoring of multiple pathogens in aquaculture.

This study presents an experimental investigation on the effects of cyclic loading waveform and cyclic stress ratio (CSR) on dynamic behaviors through laboratory tests on a source of soft clay under cyclic loading in drained condition. Test results showed that under different cyclic loading waveforms at a given frequency (f = 1 Hz) and CSR = 0.6, the axial strain increases significantly at a relatively lower number of cycles (N) and then became stable, while the axial strain consistently decreases with the increasing N and tend to be stable. At a given N, specimen under sine wave cyclic loads shows a higher axial strain rate than that under triangle wave or square cyclic loads. Test results also indicated that at different CSRs, the axial strain increases rapidly at a relatively lower N and then gradually tends to be stable with the increasing N at lower CSR yet there is no stable trend for specimens at higher CSR, which indicates there is a critical value of CSR. It is recommended to apply the cyclic loading in sine waveform with CSR close to and less than the critical value to get a better treatment effect.

Matrix metalloproteinases (MMPs) are highly expressed in leukocytes and macrophages, which play a role in the innate immune response. Here, the cDNA sequence of MMP25 from Japanese sea bass (Lateolabrax japonicus) (LjMMP25) was identified. Phylogenetic analysis revealed that LjMMP25 was most closely related to large yellow croaker MMP25. Multiple sequence alignment of LjMMP25 with MMP25 sequences from other teleosts revealed that regions of known functional importance were highly conserved. Expression analysis revealed that LjMMP25 was highly expressed in the head kidney and widely expressed in other tissues including gill, spleen, and liver. LjMMP25 was found to regulate inflammatory cytokine production and promote phagocytosis and bacterial killing in monocytes/macrophages (MO/MФ). Furthermore, LjMMP25 regulated the inflammatory response by modulating NF-κB signaling. These findings reveal new information about the role of LjMMP25 in regulating pro-inflammatory responses in this species.

This paper presents an improved method to identify the soil strata using the interval type-2 fuzzy C-means (IT2FCM) clustering algorithm representing the uncertainty in CPTu data. Representative parameters (i.e., cone resistance qt and pore pressure ratio Bq) chosen from CPTu data obtained from two engineering sites were normalized and thereafter processed by the self-written IT2FCM subprogram in MATLAB. The cluster analysis results indicated that the IT2FCM method can identify similar groups of data in the soil profile, detect different layer boundaries and transitions, and delineate the lenses and outliers within a sub-layer. Compared with the exiting cluster method, the method proposed in this study uses fewer clustering numbers, and the cluster results can discover more drastic changes within the soil strata. Combined with the validity index, the cluster results are more reasonable in identifying the soil stratigraphy.

Lysine-specific demethylase 5A (KDM5A, also named RBP2 or JARID1A) is a demethylase that can remove methyl groups from histones H3K4me1/2/3. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, drug resistance, and is associated with poor prognosis. Pharmacological inhibition of KDM5A has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of KDM5A, its role in carcinogenesis, a comparison of currently available approaches for screening KDM5A inhibitors, a classification of KDM5A inhibitors, and its potential as a drug target in cancer therapy.

Due to the lack of relevant therapies for infectious haematopoietic necrosis virus (IHNV) infection, the viral outbreak invariably causes serious economic losses in salmonid species. In this study, we evaluated the anti-IHNV effects of 7-(6-benzimidazole) coumarin (C10) and 4-phenyl-2-thioxo-1,2,3,4-tetrahydro-5H-chromeno[4,3-d]pyrimidin-5-one (S5) in vitro and in vivo. The results revealed that C10 at 12.5 mg/L and S5 at 25 mg/L significantly inhibited IHNV replication in epithelioma papulosum cyprini (EPC) cells with a maximum inhibitory rate >90%, showing that IHNV-induced cytopathic effect (CPE) was alleviated by C10 and S5. There are two complementary effects on antiviral mechanism: 1. C10 completely inhibited IHNV infectivity when the virus was preincubated with C10 at 12.5 mg/L, determining that C10 may have a negative impact on IHNV binding to the cell; 2. C10 also up-regulated the gene expression of extracellular proto type galectin-1 (Gal1-L2) and a chimera galectin-3 (Gal3-L1) of EPC cells to inhibit IHNV adhesion. For the in vivo study, injection and immersion of the coumarins enhanced the survival rate of rainbow trout (Oncorhynchus mykiss) juveniles by 25% (at least) at 12 dpi. IHNV loads in the kidney and spleen were also obviously decreased at 96 h, and thus we considered that they had a delaying effect on IHNV replication in vivo. Meanwhile, C10 with a high stability in aquacultural water in immersion suppressed IHNV horizontal transmission by decreasing the viral loads in recipient fish. Overall, our data suggest that there is a positive effect of C10 and S5 against IHNV infection in aquaculture, and C10 had the potential to be a broad-spectrum antiviral against fish rhabdoviruses.

Interleukin-6 (IL-6) is one of the most pleiotropic cytokines because of its wide range of effects on cells of the immune and non-immune systems in the body. However, the role of IL-6 in fish monocytes/macrophages (MO/MФ) is poorly understood. In this study, we cloned the cDNA sequence of the IL-6 gene from ayu (Plecoglossus altivelis) and demonstrated using a tissue distribution assay that ayu interleukin-6 (PaIL-6) mRNA is expressed in all tested tissues. Changes in expression were observed in immune tissues as well as in MO/MФ after a Vibrio anguillarum infection; subsequently, PaIL-6 was expressed and purified to prepare anti-PaIL-6 antibodies. Recombinant PaIL-6 protein (rPaIL-6) treatment enhanced pro-inflammatory cytokine expression. Ayu interleukin-6 receptor β (PaIL-6Rβ) knockdown resulted in decreased pro-inflammatory cytokine expression in MO/MФ treated with rPaIL-6, whereas no significant changes were observed after ayu interleukin-6 receptor α (PaIL-6Rα) knockdown in MO/MФ. PaIL-6 and PaIL-6Rβ knockdown in MO/MФ inhibited the phosphorylation of signal transducer and activator of transcription 1. Moreover, PaIL-6Rβ knockdown inhibited the phagocytic and bactericidal ability of ayu MO/MФ treated with rPaIL-6. These data indicate that PaIL-6 may be able to regulate the function of ayu MO/MФ.

This paper presents an improved method for predicting the bearing capacity of single jacked pile based on piezocone penetration test (CPTu) data which contain tip resistance (qt), side friction (fs) and excess dynamic pore water pressure (u2). Firstly, the average value of qt was determined to calculate the pile unit base resistance according to the influence zone of the logarithmic spiral concerning the effect of soil types. Secondly, fs and u2 were used to calculate the pile unit shaft resistance considering the effect of friction fatigue. The pile jacking force was obtained in terms of unit base resistance and unit shaft resistance. The ultimate bearing capacity was finally determined using pile jacking force multiplied by a force ratio denoted as Rf. The ultimate bearing capacities calculated for two case projects show a good agreement with the measured results, which indicates that the proposed method is feasible and effective. Reliability assessment was carried out on the proposed method and other five estimation methods with respect to the reliability index obtained by advanced first-order second-moment (AFOSM) method. Comparison result showed that the method proposed in this study has a higher reliability index over other five existing methods. Therefore, the proposed method can be used as a reliable alternative to predict the bearing capacity in the engineering practice of jacked pile foundation.

As an efficient pathogen resulting in economic impact in aquaculture, spring viremia of carp virus (SVCV) causes devastating disease in cyprinids. Based on the previous study that 7-(6-(2-methyl-imidazole))-coumarin (D5) exhibited anti-SVCV activity in fish cells, we hypothesized that D5 may be useful as a potential therapeutic agent for controlling SVCV infection in vivo. In this study, we verified that D5 inhibited SVCV replication in zebrafish, with reducing 22.5% mortality of SVCV-infected fish. Further data suggested that coumarin D5 was more stable with a prolonged inhibitory half-life in the early stage of virus infection (1-4 days). Consistent with above results, D5 decreased the viral titer in fish body and repressed SVCV glycoprotein gene expression in virus sensitive tissues (kidney and spleen) in the early stage of virus infection. In addition, the results replied that D5 elicited an innate immune response in non-viral infected zebrafish by up-regulating the expression of interferon genes (IFNγ, IFNφ1, IFNφ2 and RIG-1). D5 also enhanced the levels of antioxidant-related gene transcription and enzyme activities in SVCV-infected zebrafish, suggesting that D5 exhibited an antioxidant protection on fish by keeping the balance of redox state. Therefore, D5 is a potential therapeutic agent for the devastating fish rhabdovirus infections.

Background: On the most elementary level, you and I (human beings) were created with five main mechanisms (or parts): • A body which is termed as the main structure of the human being. • A sensory system that takes certain information around the body and the immediate environment. • A muscle system to aid the body move easily. • A control base to trigger the muscles and sensors. • A brain system that develops sensory data and tells the muscles what to do in other words the way forward. Obviously, we likewise have some imperceptible qualities, for example, intellect and ethics, among others but on an absolute corporeal level. Robots, on the other hand, can be created with five main mechanisms or more. Objectives: This research aims at implementing robots in some tedious jobs that as supposed to be executed by human beings in various factories and industries. This study also presents the practical and tentative model for Extenics replications of the moveable mechanical device (robot) useful on VIPRO stage. Methods: Momentary antiquity and indication of the pertinent hypothetical ideas are provided. The intelligent boundary for drawn-out switch uses a novel element for synthetic intelligence which is drawn-out control (Extenics) to expand DHFPC switch rapid enactment of mobile robots. Result: Applying Extenics specific methods and application in vague interplanetary result in a novel, advanced application for the VIPRO stage which can be used to feign and device innovative switch approaches of moveable robots.

In this study, the dynamic response of a periodic viaduct to a moving mass is investigated. In view of the periodicity of the viaduct, the mass-viaduct interaction force is expanded into a Fourier series first, each term of which represents one component of the interaction force. By using the Fourier transform method and finite element method (FEM), the frequency domain response of the periodic viaduct to each interaction force component is obtained. The time domain response of the periodic viaduct to the force component can be recovered by applying the inverse Fourier transform to the corresponding frequency domain response. With the mass-viaduct coupling condition and the time domain response of the viaduct to the force component, the Fourier coefficients of the mass-viaduct interaction force are obtained. Superposing the responses of the periodic viaduct due to all the interaction force components yields the response of the periodic viaduct to the moving mass. Numerical results show that the force-weight ratio increases with increasing mass and speed of the mass, suggesting that the inertial effect of the moving mass should be taken into account for the large mass with high speeds. Also, it is found that for the case of the large moving mass with high speeds, the mass-viaduct interaction force may become negative, indicating that the mass has a tendency to separate from the viaduct in this case.

Coumarin forms an elite class of naturally occurring compounds that possess promising antiviral therapeutic perspectives. In the previous study, we designed and synthesized a coumarin derivative, 7-(4-benzimidazole-butoxy)-coumarin (BBC), to evaluate its antiviral activity on spring viraemia of carp virus (SVCV). In this study, our results show that BBC does not affect viral adhesion and delivery from endosomes to the cytosol, indicating BBC has no inhibitory activity in the early stage of viral infection. Further data are determined that BBC significantly declines SVCV-infected apoptosis and recovers caspase-3/8/9 activity. To reveal the pathway that affects Nrf2 translocation by BBC, we examine changes in protein kinase C (PKC) in EPC cells treated with BBC. We observe that BBC results in a higher phosphorylation of PKCα/β that is involved in the activation of erythroid 2-related factor 2 (Nrf2) phosphorylation to favor Nrf2 translocation to nucleus at 24 and 48 h. In addition, the results show that BBC also up-regulates both antiviral responses, heme oxygenase-1 (HO-1) expression and cellular IFN response. Overall, this mechanism of action provides a new therapeutic target for the treatment of SVCV infection, and these results suggest that treatment with BBC is effective in reducing SVCV infection and differently regulates SVCV-induced undesirable conditions.

Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily, contributing to inflammation, apoptosis, and differentiation. However, the function of OPG in the host immune system of teleosts remains unclear. Here, we cloned the cDNA of the LcOPG gene from large yellow croaker. LcOPG mRNA was expressed in all analyzed tissues and was upregulated by Vibrio alginolyticus infection in immune tissues and monocytes/macrophages (MO/MФ). Subsequently, the LcOPG protein was expressed and purified using a prokaryotic expression system. Recombinant LcOPG protein (rLcOPG) treatment suppressed V. alginolyticus-induced pro-inflammatory cytokine and enhanced V. alginolyticus-induced anti-inflammatory cytokine mRNA expression. Furthermore, rLcOPG decreased V. alginolyticus-induced MO/MФ apoptosis. Therefore, the results indicate that LcOPG might play a role in the immune response of V. alginolyticus-infected large yellow croaker.

Histone methylation is a key posttranslational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, transcriptional regulation, and epigenetic inheritance. Variations in the pattern of histone methylation influence both physiological and pathological events. Lysine-specific demethylase 5A (KDM5A, also known as JARID1A or RBP2) is a KDM5 Jumonji histone demethylase subfamily member that erases di- and tri-methyl groups from lysine 4 of histone H3. Emerging studies indicate that KDM5A is responsible for driving multiple human diseases, particularly cancers. In this review, we summarize the roles of KDM5A in human cancers, survey the field of KDM5A inhibitors including their anticancer activity and modes of action, and the current challenges and potential opportunities of this field.

Virus-encoded tumor necrosis factor receptors (vTNFRs) facilitate viral escape from the host immune response during viral propagation. Cyprinid Herpesvirus-2 (CyHV-2) is a double-stranded DNA virus of alloherpesviridae family that causes great economic losses in the aquaculture industry. The present study identified and characterized a novel TNFR homolog termed ORF4 in CyHV-2. ORF4 was identified as a secreted protein and a homolog of herpesvirus entry mediator (HVEM). ORF4 localized to the cytoplasm in infected GiCF cells. ORF4 overexpression enhanced viral propagation, while downregulation of ORF4 via siRNA decreased viral propagation. ORF4 overexpression promoted GiCF proliferation, and its downregulation suppressed CyHV-2-induced apoptosis. GST-pulldown and LC-MS/MS assays identified 44 conditional binding proteins that interact with ORF4 protein, while the GST pulldown test did not support the idea that ORF4 interact with histone H3.3. Taken together, our results contribute to our understanding of the vTNFR function in alloherpesviridae pathogenesis and host immune regulation.

Adrenocorticotropic hormone (ACTH), a bioactive peptide of the family of melanocortins, is generated from pro-opiomelanocortin (POMC). So far, the research on the specific functions of ACTH in the immune system of teleosts is limited. We determined two complementary DNA (cDNA) sequences of POMC in ayu (Plecoglossus altivelis), termed PaPOMC-A and PaPOMC-B. PaPOMCs transcripts occurred in all examined tissues, and their expression in immune tissues changed following experimental infection with Vibrio anguillarum. PaACTH-B, but not PaACTH-A, suppressed the phagocytosis of monocytes/macrophages (MO/MФ). Two isoforms of PaACTH increased the bactericidal capacity of MO/MФ. PaACTH-A increased anti-inflammatory cytokine expression, while PaACTH-B decreased pro-inflammatory cytokine expression in MO/MФ. Compared with PaACTH-B treatment, the PaACTH-A treatment improved survival rate and reduced the bacterial load in V. anguillarum-infected ayu through interleukin (IL)-10. Our results indicate that the two PaACTH isoforms exert different effects in the host defense against bacterial infection.

Direct numerical simulations of the dynamic response of the phononic crystal to point or distributed forces via conventional numerical methods are still formidable currently due to large number of DOFs involved in the simulations. In this study, based on the plane wave expansion (PWE) method, a plane wave finite element (PWFE) model for the 2-D phononic crystal which is infinite in the horizontal direction and finite in the vertical direction and subjected to a point harmonic force is proposed. To this end, the point harmonic force is decomposed into the wavenumber domain (WND) components by the Fourier transform first. The variables of the 2-D phononic crystal under the WND force component are expanded into a series of plane waves along the horizontal direction, and the variables associated with each plane wave are discretized by the FE method in the vertical direction. By using the virtual work principle, FE equations for the plane waves of the phononic crystal are established. With the FE equations for the plane waves, the eigenvalue equation for the displacement of the plane waves and wavenumber is formulated. Superposing the eigenvectors of the above eigenvalue equation yields the displacement for the plane waves due to the WND force component. Synthetization of the contributions from all the plane waves and inversion of the Fourier transform with respect to the wavenumber via the contour integration method generate the response of the phononic crystal to the point force. Comparison of present results with those due to the transfer matrix method validates the proposed model. Also, presented numerical results suggest that the dynamic response of the phononic crystal to a point harmonic force exhibits remarkable resonance phenomenon.

The white spot syndrome virus (WSSV) is an efficiently destructive pathogen in shrimp farming, which has contributed to enormous economic losses in the global shrimp sector. After antiviral activity screening in our small molecule drug library, we found a medicine, 2-amino-4-(4-hydroxy-3-methoxyphenyl)-5-oxo-4H,5H-pyrano [3,2-c] chromene-3‑carbonitrile (serial number: Coumarin 3004), significantly inhibited WSSV replication in Litopenaeus vannamei and reduced the mortality of WSSV-infected L. vannamei. The data indicated that the replication inhibition of WSSV exceeded 60% after WSSV particles pre-incubation with 10 mg/L Coumarin 3004 for 4 h. Moreover, Coumarin 3004 showed a stable efficacy for two days in aquacultural water, which provided a potential for its aquaculture application. The approach of consecutive Coumarin 3004 changes further decreased the mortality of WSSV-infected L. vannamei, which allows novel possibilities for treating WSSV infection. Meanwhile, up-regulation of four antimicrobial peptides (AMPs) related gene expressions revealed that Coumarin 3004 may promote AMPs-related expressions and inhibit WSSV replication. Although Coumarin 3004 blocked the horizontal transmission of WSSV in a cohabitation model, it did not entirely block the transmission. Taken together, Coumarin 3004 is a potentially excellent therapeutic agent against WSSV propagation in shrimp farming.

Objective:In this paper, an integral equation model is established to predict the time-dependent response of a vertically loaded pile embedded in a layered Transversely Isotropic Saturated Soil (TISS).Methods:Based on the fictitious pile method, the pile-soil system is decomposed into an extended saturated half-space and a fictitious pile. The extended half-space is treated as a layered TISS, while the fictitious pile is considered as a 1D bar. The pile-soil compatibility is accomplished by requiring that the axial strain of the fictitious pile be equal to the vertical strain of the extended layered TISS along the axis of the pile. The second kind Fredholm integral equation of the pile is then derived by using the aforementioned compatibility condition and the fundamental solution of the layered TISS, which is equivalent to the solution of the layered TISS subjected to a uniformly-distributed load acting vertically over a circular area with the radius equal to that of the pile. The fundamental solution of the layered TISS is obtainedviathe Reflection-Transmission Matrix (RTM) method for the layered TISS. Applying the Laplace transform to the Fredholm integral equation, and solving the resulting integral equation, the transformed solution is obtained. The time domain solution of the pile-soil system is retrievedviathe inverse Laplace transform.Results and Conclusion:Numerical results of this paper agree with existing solutions very well, validating the proposed pile-soil interaction model. A parametric study is carried out to examine the influence of some parameters on the response of the pile-soil system.

A model for predicting the frost-heave effect on a single pile embedded in the frozen soil is proposed in this study. In the model, the half-space saturated soil is considered to be composed of an overlying soil layer denoting the frozen layer and underlying layers denoting the unfrozen layers. In the absence of the pile, the free frost-heave strain is assumed to occur only in the overlying frozen layer. The total strain field of the layered soil is equal to the superposition of the free frost-heave strain and the disturbed strain due to the presence of the pile. According to the Muki's fictitious pile method, the pile and frozen soil are supposed to be compatible at the pile-soil interface and no slide hence occurs at the interface, which is accomplished by assuming the equivalence of the vertical strains of the fictitious pile and soil. Based on the Muki's method, the second kind of Fredholm integral equation for the pile is established using the aforementioned pile-soil compatibility condition and the fundamental solution for the layered saturated soil. The fundamental solution of the layered saturated soil is obtained by means of the reflection and transmission matrix (RTM) method. Numerical results obtained by the proposed model for the pile are consistent with existing numerical and experimental results, validating the proposed model. With the proposed model, parametric studies are conducted to examine the influence of the freezing depth of the soil on the axial force and vertical displacement of the pile as well as the tangential force acting on the pile and the pore pressure of the pile-side soil. Numerical results show that the frost-heave axial force, tangential force, vertical displacement and pore pressure are all increased with increasing freezing depth.

Hypoxia-inducible factor-1α (HIF-1α) plays a critical role in immune and inflammatory responses and is important in controlling a variety of processes in monocytes and macrophages. However, the role of HIF-1α in the teleost immune system remains less known. In this study, we cloned the cDNA sequence of HIF-1α from the ayu (Plecoglossus altivelis, PaHIF-1α). Sequence and phylogenetic tree analysis showed that PaHIF-1α clustered within the fish HIF-1α tree and was closely related to that of Northern pike (Esox lucius). PaHIF-1α was expressed in all tested tissues and expression increased in liver, head kidney, and body kidney upon Vibrio anguillarum infection. PaHIF-1α was found to regulate the expression of cytokines in ayu monocytes/macrophages (MO/MФ). PaHIF-1α mediated hypoxia-induced enhancement of MO/MФ phagocytic and bactericidal activities to enhance host defenses. Compared with the control, intermittent hypoxia further increased the expression of PaHIF-1α mRNA, improved the survival rate, and reduced the bacterial load of V. anguillarum-infected ayu. Therefore, PaHIF-1α may play a predominant role in the modulation of ayu MO/MФ function.

The dynamic response of an infinitely long circular tunnel embedded in the saturated soil to a series of equidistant moving loads (SEML) is investigated in this study. The saturated soil surrounding the tunnel is described by Biot’s theory. Two scalar potentials and one vector potential are introduced to represent the displacement of the solid skeleton and the pore pressure. Based on Biot’s theory, the Helmholtz equations for the potentials are derived using the Fourier transform method. Performing the Fourier transform with respect to the longitudinal coordinate on the Helmholtz equations gives the frequency–wavenumber domain general solutions for the potentials. With the general solutions and the boundary conditions along the tunnel surface, the solution for the circular tunnel subjected to a single moving load (SML) is obtained. Superposition of the solutions for SMLs gives the representation for the response of the tunnel to a SEML, with which the resonance and cancelation conditions for the SEML are derived. Numerical simulations suggest that for the circular infinite tunnel there is a critical velocity. When the load moves with the critical velocity, the frequency domain response of the tunnel exhibits some dominant peak. Further, for a SEML moving with the critical velocity, the resonance and cancelation phenomena in the time domain may occur when the aforementioned resonance and cancelation conditions are fulfilled.

Geometrical nonlinearity of the soft soil and the deviation of water flow in the soft clay from Darcy’s law have been well recognized in practice. However, the theory of consolidation, which can account for both the geometrical nonlinearity and the non-Darcian flow, has not been reported so far. In this contribution, a model for the consolidation of soft clay which can allow for these two factors simultaneously is proposed. Utilizing the finite difference method, the numerical model for this problem is developed. With the numerical model, the effects of the geometrical nonlinearity and the non-Darcian flow on the consolidation of the soft soil are investigated. The results show that when the self-weight stress is calculated by the same method, the rate of the non-Darcian consolidation for the large-strain case is larger than that for the small-strain case, but the difference between them is limited. However, the difference between the consolidation rates caused by the non-Darcian and Darcian flows is significant. Therefore, when the geometrical nonlinearity of the soft clay is considered in calculating the consolidation settlement, due to the complexity of the large-strain assumption, the small-strain assumption can be used to replace it if the self-weight stress for the small-strain assumption is calculated by considering its sedimentation. However, due to the aforementioned large difference between the consolidation rates with consideration of the non-Darcian flow in soft clay or not, it is better to consider the non-Darcian flow law for both the small and large stain assumptions.

Salinity stress have detrimental effect on teleosts and may increase susceptibility to disease. Betaine is a compound utilized by organisms to regulate osmotic pressure and plays an important role in the immune response and anti-inflammatory functions. Here, the protective effects of betaine against Vibrio anguillarum infection of ayu under conditions of salinity was determined. A total of 60 ayu were cultured at 10 ppt salinity for 14 days, all fish were intraperitoneally injected with 100 μL of 100 or 200 mg/kg of betaine or saline on days 0, 2, 4, and 6. The fish were subsequently infected with V. anguillarum. The results showed that betaine treatment improved the survival rate of V. anguillarum-infected ayu. Betaine treatment decreased the bacterial load and histological damage in the head-kidney, liver, and spleen. Besides, the inflammatory response was decreased by betaine in V. anguillarum-infected ayu tissues and monocytes/macrophages (MO/MФ). Furthermore, in hypertonic-exposed MO/MФ (19 mOsm), betaine treatment enhanced phagocytosis activity and promoted the bacterial killing capability. Finally, we found that betaine mediated the inflammatory response through BGT-1 in V. anguillarum-infected ayu MO/MФ. In conclusion, when exposed to osmotic stress, betaine was able to mediate the host defense in ayu and modulate the antibacterial response through MO/MФ.

In this paper, the resonance and cancellation phenomena occurring in a periodic structure-- a pile-supported periodic viaduct subjected to multiple equidistant moving loadings (MEML) are investigated. For this purpose, the representation for the dynamic response of the periodic viaduct to a single moving loading (SML) is introduced first. In order to take account of the pile-soil-structure interaction when evaluating the response of the periodic viaduct to a SML, a wavenumber domain boundary element method (WDBEM) model for the pile-row-soil system is employed to determine the compliances of the piles. By superposing the responses of the viaduct to all SMLs constituting the MEML, the representation for the dynamic response of the periodic viaduct to the MEML is obtained. With the representation for the MEML response of the viaduct, the resonance and cancellation conditions for the viaduct are derived. For the high speed MEML, when the time interval between two neighboring moving loadings is equal to the integer or half-integer multiples of the period of one of the dominant resonance peaks of the corresponding SML response of the viaduct, resonance or cancellation occurs. The predicted resonance and cancellation phenomena are confirmed by the numerical results presented in this paper.