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Porcine epidemic diarrhea virus (PEDV) belongs to the genus Alphacoronavirus of the Coronaviridae family and can cause fatal watery diarrhea in piglets, causing significant economic losses. Heterogeneous nuclear protein U (HNRNPU) is a novel RNA sensor involved in sensing viral RNA in the nucleus and mediating antiviral immunity. However, it remains elusive whether and how cytoplasmic PEDV can be sensed by the RNA sensor HNRNPU. In this study we determined that HNRNPU was the binding partner of Nsp13 by immunoprecipitation-liquid chromatography-tandem mass spectrometry (IP/LC-MS/MS) analysis. The interaction between Nsp13 and HNRNPU was demonstrated by using coimmunoprecipitation and confocal immunofluorescence. Next, we identified that HNRNPU expression is significantly increased during PEDV infection, whereas the transcription factor hepatocyte nuclear factor 1α (HNF1A) could negatively regulate HNRNPU expression. HNRNPU was retained in the cytoplasm by interaction with PEDV Nsp13. We found that HNRNPU overexpression effectively facilitated PEDV replication, while knockdown of HNRNPU impaired viral replication, suggesting a promoting function of HNRNPU to PEDV infection. Additionally, HNRNPU was found to promote PEDV replication by affecting TRAF3 degradation at the transcriptional level to inhibit PEDV-induced beta interferon (IFN-ß) production. Mechanistically, HNRNPU downregulates TRAF3 mRNA levels via the METTL3-METTL14/YTHDF2 axis and regulates immune responses through YTHDF2-dependent mRNA decay. Together, our findings reveal that HNRNPU serves as a negative regulator of innate immunity by degrading TRAF3 mRNA in a YTHDF2-dependent manner and consequently facilitating PEDV propagation. Our findings provide new insights into the immune escape of PEDV. IMPORTANCE PEDV, a highly infectious enteric coronavirus, has spread rapidly worldwide and caused severe economic losses. During virus infection, the host regulates innate immunity to inhibit virus infection. However, PEDV has evolved a variety of different strategies to suppress host IFN-mediated antiviral responses. Here, we identified that HNRNPU interacted with viral protein Nsp13. HNRNPU protein expression was upregulated, and the transcription factor HNF1A could negatively regulate HNRNPU expression during PEDV infection. HNRNPU also downregulated TRAF3 mRNA through the METTL3-METTL14/YTHDF2 axis to inhibit the production of IFN-ß and downstream antiviral genes in PEDV-infected cells, thereby promoting viral replication. Our findings reveal a new mechanism with which PEDV suppresses the host antiviral response.
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Infecções por Coronavirus , Proteínas Nucleares , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Replicação Viral , Animais , Linhagem Celular , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Proteínas Nucleares/metabolismo , Vírus da Diarreia Epidêmica Suína/fisiologia , RNA Mensageiro/metabolismo , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/virologia , Fator 3 Associado a Receptor de TNF/metabolismo , Fatores de Transcrição/metabolismo , Replicação Viral/fisiologiaRESUMO
Porcine epidemic diarrhoea (PED) caused by porcine epidemic diarrhoea virus (PEDV) has led to significant economic losses in the swine industry worldwide. Histone Cluster 2, H2BE (HIST2H2BE), the main protein component in chromatin, has been proposed to play a key role in apoptosis. However, the relationship between H2BE and PEDV remains unclear. In this study, H2BE was shown to bind and interact with PEDV nonstructural protein 9 (Nsp9) via immunoprecipitation-mass spectrometry (IP-MS). Next, we verified the interaction of Nsp9 with H2BE by immunoprecipitation and immunofluorescence. H2BE colocalized with Nsp9 in the cytoplasm and nuclei. PEDV Nsp9 upregulated the expression of H2BE by inhibiting the expression of IRX1. We demonstrated that overexpression of H2BE significantly promoted PEDV replication, whereas knockdown of H2BE by small interfering RNA (siRNA) inhibited PEDV replication. Overexpression of H2BE led to significantly inhibited GRP78 expression, phosphorylated PERK (p-PERK), phosphorylated eIF2 (p-eIF2), phosphorylated IRE1 (p-IRE1), and phosphorylated JNK (p-JNK); negatively regulated CHOP and Bax expression and caspase-9 and caspase-3 cleavage; and promoted Bcl-2 production. Knocking down H2BE exerted the opposite effects. Furthermore, we found that after deletion of amino acids 1-28, H2BE did not promote PEDV replication. In conclusion, these studies revealed the mechanism by which H2BE is associated with ER stress-mediated apoptosis to regulate PEDV replication. Nsp9 upregulates H2BE. H2BE plays a role in inhibiting apoptosis and thus facilitating viral replication, which depends on the N-terminal region of H2BE (amino acids 1-28). These findings provide a reference for host-PEDV interactions and offer the possibility for developing strategies for PEDV decontamination and prevention.
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Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Animais , Suínos , Chlorocebus aethiops , Vírus da Diarreia Epidêmica Suína/fisiologia , Fator de Iniciação 2 em Eucariotos , Proteínas não Estruturais Virais/genética , Replicação Viral , Proteínas Serina-Treonina Quinases , Aminoácidos , Estresse do Retículo Endoplasmático , Apoptose , Infecções por Coronavirus/veterinária , Células VeroRESUMO
BACKGROUND: Porcine Epidemic Diarrhea Virus (PEDV) is a coronavirus that seriously affects the swine industry. MicroRNAs and long noncoding RNAs are two relevant non-coding RNAs (ncRNAs) class and play crucial roles in a variety of physiological processes. Increased evidence indicates a complex interaction between mRNA and ncRNA. However, our understanding of the function of ncRNA involved in host-PEDV interaction is limited. RESULTS: A total of 1,197 mRNA transcripts, 539 lncRNA transcripts, and 208 miRNA transcripts were differentially regulated at 24 h and 48 h post-infection. Gene ontology (GO) and KEGG pathway enrichment analysis showed that DE mRNAs and DE lncRNAs were mainly involved in biosynthesis, innate immunity, and lipid metabolism. Moreover, we constructed a miRNA-mRNA-pathway network using bioinformatics, including 12 DE mRNAs, 120 DE miRNAs, and 11 pathways. Finally, the target genes of DE miRNAs were screened by bioinformatics, and we constructed immune-related lncRNA-miRNA-mRNA ceRNA networks. Then, the selected DE genes were validated by qRT-PCR, which were consistent with the results from RNA-Seq data. CONCLUSIONS: This study provides the comprehensive analysis of the expression profiles of mRNAs, lncRNAs, and miRNAs during PEDV infection. We characterize the ceRNA networks which can provide new insights into the pathogenesis of PEDV.
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MicroRNAs , Vírus da Diarreia Epidêmica Suína , RNA Longo não Codificante , Animais , Redes Reguladoras de Genes , MicroRNAs/genética , MicroRNAs/metabolismo , Vírus da Diarreia Epidêmica Suína/genética , Vírus da Diarreia Epidêmica Suína/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , SuínosRESUMO
Infection with the porcine epidemic diarrhoea virus (PEDV) causes severe enteric disease in suckling piglets, causing massive economic losses in the swine industry worldwide. Tripartite motif-containing 56 (TRIM56) has been shown to augment type I IFN response, but whether it affects PEDV replication remains uncharacterized. Here we investigated the role of TRIM56 in Marc-145 cells during PEDV infection. We found that TRIM56 expression was upregulated in cells infected with PEDV. Overexpression of TRIM56 effectively reduced PEDV replication, while knockdown of TRIM56 resulted in increased viral replication. TRIM56 overexpression significantly increased the phosphorylation of IRF3 and NF-κB P65, and enhanced the IFN-ß antiviral response, while silencing TRIM56 did not affect IRF3 activation. TRIM56 overexpression increased the protein level of TRAF3, the component of the TLR3 pathway, thereby significantly activating downstream IRF3 and NF-κB signalling. We demonstrated that TRIM56 overexpression inhibited PEDV replication and upregulated expression of IFN-ß, IFN-stimulated genes (ISGs) and chemokines in a dose-dependent manner. Moreover, truncations of the RING domain, N-terminal domain or C-terminal portion on TRIM56 were unable to induce IFN-ß expression and failed to restrict PEDV replication. Together, our results suggested that TRIM56 was upregulated in Marc-145 cells in response to PEDV infection. Overexpression of TRIM56 inhibited PEDV replication by positively regulating the TLR3-mediated antiviral signalling pathway. These findings provide evidence that TRIM56 plays a positive role in the innate immune response during PEDV infection.
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Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Animais , Antivirais , Interferon beta/genética , Interferon beta/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Suínos , Fator 3 Associado a Receptor de TNF/genética , Fator 3 Associado a Receptor de TNF/metabolismo , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/metabolismo , Replicação ViralRESUMO
Hot film sensors detect the flow shear stress based on the forced convection heat transfer to the fluid. Current hot film sensors have been significantly hindered by the relatively low sensitivity due to the massive heat conduction to the substrate. This paper describes the design, fabrication, simulation, and testing of a novel flow sensor with dual-layer hot film structures. More specifically, the heat conduction was insulated from the sensing heater to the substrate by controlling both sensing and guarding heaters working at the same temperature, resulting in a higher sensitivity. The experiment and simulation results showed that the sensitivity of the dual-layer hot film sensor was significantly improved in comparison to the single-layer sensor. Additionally, the dual-layer sensor was designed and fabricated in an integrated, flexible, and miniaturized manner. Its small size makes it an excellent candidate for flow detection.
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Climate change and urbanization strongly affect the variations of terrestrial net primary production (NPP), but the relative contributions of these two factors to NPP changes have not been determined yet (especially on a macroscale). In this study, spatial-temporal variations of NPP in China from 2000 to 2010 were estimated using the Carnegie-Ames-Stanford Approach model, and the effects induced by urbanization and climate change were quantified. The obtained results showed that during the study period, the NPP in China exhibited an annual increase of 0.03â¯Pgâ¯C accompanied by large spatial heterogeneities. During the whole study period, the urban area in China increased by 16.44â¯×â¯103â¯km2, and the corresponding NPP losses amounted to 11.60â¯×â¯10-3â¯Pgâ¯C. Urban expansion significantly offset the climate change-induced NPP increases and worsened NPP decreases (the offsetting ratio calculated for China was 5.42%, and its exact magnitudes varied by province). The largest NPP variations were observed over the regions with rapid urban expansion, whose contribution ratio was 32.20% for China and exceeded 30% for most provinces. Climate change contributed considerably to the NPP variations in both the newly urbanized (30.45%) and purely vegetated (46.92%) areas, but its contribution ratios were slightly lower than those of residual factors. Moreover, climate change strongly affected the NPP levels over the arid and semi-arid regions as well as over the Tibet Plateau; however, residual factors dominated the NPP variations over the central and southeast China. Our study highlights a significant role of urbanization in driving terrestrial NPP variations on a macroscale and provides a new perspective on disentangling the impacts of external factors on NPP values.
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Mudança Climática , Urbanização , China , Ecossistema , TibetRESUMO
Fine particulate matter (PM2.5) and sulfur dioxide (SO2) are 2 common air pollutants, but their toxicological effects of coexposure are still not fully clear. In this study, SO2 exposure (5.6 mg/m3) couldn't cause obvious inflammatory responses in rat lungs. The PM2.5 exposure (1.5 mg/kg body weight) increased inflammatory cell counts in bronchoalveolar lavage fluid (BALF) and some inflammation damage. Importantly, SO2 and PM2.5 (1.5, 6.0, and 24.0 mg/kg) coexposure induced pathological and ultrastructural damage and raised inflammatory cells in BALF compared with the control. Also, they significantly elevated the levels of pro-inflammatory cytokines, adhesion molecule, and nitric oxide (NO) and promoted the gene expression of nuclear factor kappa B (NF-κB), phosphorylated p38 (p-p38), and Toll-like receptor 4 (TLR4) in rat lungs treated with higher dose of PM2.5 (6.0 and 24.0 mg/kg) plus SO2 relative to the control or SO2 group, along with the decreased inhibitor of NF-κBα and increased inhibitor of NF-κB kinase ß expressions. The changes in the inflammatory markers in the presence of PM2.5 plus SO2 were not significant compared with the PM2.5 group. The results indicated that inflammatory injury and pathological and ultrastructural damage in rat lungs exposed to PM2.5 plus SO2 were involved in TLR4/p38/NF-κB pathway activation accompanied by oversecretion of pro-inflammatory cytokine, adhesion molecule, and NO. It provides more useful evidence to understand the possible toxicological mechanism that PM2.5 and SO2 copollution exacerbate lung disease.
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Poluentes Atmosféricos/toxicidade , Pulmão/efeitos dos fármacos , Material Particulado/toxicidade , Dióxido de Enxofre/toxicidade , Animais , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Citocinas/genética , Citocinas/imunologia , Interações Medicamentosas , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/imunologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/ultraestrutura , Masculino , Microscopia Eletrônica de Transmissão , NF-kappa B/imunologia , Óxido Nítrico/imunologia , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/imunologia , RNA Mensageiro/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/imunologiaRESUMO
New developments are made in the resonant fiber optic gyro (RFOG), which is an optical sensor for the measurement of rotation rate. The digital signal processing system based on the phase modulation technique is capable of detecting the weak frequency difference induced by the Sagnac effect and suppressing the reciprocal noise in the circuit, which determines the detection sensitivity of the RFOG. A new technique based on the sinusoidal wave modulation and square wave demodulation is implemented, and the demodulation curve of the system is simulated and measured. Compared with the past technique using sinusoidal modulation and demodulation, it increases the slope of the demodulation curve by a factor of 1.56, improves the spectrum efficiency of the modulated signal, and reduces the occupancy of the field-programmable gate array resource. On the basis of this new phase modulation technique, the loop is successfully locked and achieves a short-term bias stability of 1.08°/h, which is improved by a factor of 1.47.
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A novel hybrid single-polarization (SP) fiber ring resonator is demonstrated by using a polarization-maintaining coupler formed by splicing a section of SP fiber into the resonator. The SP fiber selectively eliminates the unwanted resonance by introducing high loss for the unwanted eigenstates of polarization in the resonator. The calculated result shows that this hybrid SP resonator is a good candidate for a tactical-grade performance gyro with a high environmental temperature stability. The experiment shows that the desired resonance in the resonator can keep an excellent stability in a wide temperature range, thus the temperature-dependent polarization-fluctuation drift in the resonant fiber optic gyro is sufficiently suppressed. As a result, a random walk coefficient of 0.08°/âh and a typical bias stability below 0.3°/h for an integration time of 300 s have been carried out.
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For the first time, a significant noise source in the resonant fiber optic gyroscope (RFOG) called intermodulation induced error is proposed and deeply analyzed in this paper. The intermodulation error is produced by the laser frequency noise at even multiples of the modulation frequency due to an intermodulation effect, which will seriously limit the random noise performance of the RFOG. Experiments are designed and conducted to verify and measure the intermodulation induced error in the RFOG. The experimental results confirm the existence of intermodulation error, and fit well with the theory. As for the design of the RFOG, light sources with a narrow intrinsic linewidth and a high modulation frequency are preferable to achieve a high rotation-rate sensitivity.
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A novel hybrid polarization-maintaining (PM) air-core photonic bandgap fiber (PBF) ring resonator is firstly demonstrated by using a conventional solid-core PM fiber optical coupler formed by splicing a section of PM air-core PBF into the resonator. Due to Fresnel reflections exist at the two junctions between the air-core PBF and the solid-core fiber, the forward output signal of this hybrid ring resonator is the normal resonant curve with the superposition of the lightwaves that experienced even numbers of Fresnel reflections and the backward output signal is composed of lightwaves that experienced odd numbers of Fresnel reflections. Rigorous derivations of the forward and backward output signals are given out. The biggest resonant depth and finesse of the hybrid air-core PBF ring resonator predicted are 0.352 and 6.3 respectively by assuming a splice loss of 1.8 dB per junction. These predictions are finally confirmed by testing both the forward and backward output signals of the hybrid ring resonator. With the countermeasures against the influences of the odd numbers of Fresnel reflections, a bias stability of 0.007°/s is successfully demonstrated in a hybrid PM air-core PBF ring-resonator gyro.
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The accuracy of the resonant frequency servo loop is a major concern for high-performance operation of a resonant fiber optic gyro. This is usually resolved by adopting the central frequency of the laser source to track the resonance of the optical fiber ring resonator in one direction. However, the drift of the resonant frequency arising from resonator temperature fluctuation must be eliminated to maintain this accuracy. The traditional proportional integral (PI) frequency servo loop cannot address this issue very well. For instance, a bias error as large as tens or even hundreds of degrees/hour has been observed at the demodulated output of a resonant frequency servo loop. In this paper, we propose a method to eliminate this bias error by adding a double integral term in the traditional PI-based resonant frequency servo loop. We demonstrate that the double integral term can precisely track the linear resonant frequency drift, evidenced by our experimentally achieved close-to-zero bias error of -0.0009 deg/h at the demodulated output of the resonant frequency servo loop.
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Arctigenin, a natural product with diverse pharmacological activities, can inhibit cell proliferation and survival and has shown promising potential in cancer research. In this study, we designed a series of arctigenin derivatives with HDAC inhibitory activity based on the synergistic effects between HDAC inhibitors and arctigenin. Among them, compound B7 exhibited significantly higher antiproliferative activity in the MV411 cell line compared to the positive control, tucidinostat. Additionally, enzymatic activity testing was performed with compound B7. Further mechanistic studies indicated that compound B7 induced apoptosis through the Caspase-3 pathway in MV411 cells and enhanced histone acetylation levels in the MV411 cell line. These findings highlight the broad potential application of these arctigenin derivatives in cancer therapy.
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Vegetation greening has been suggested to be a dominant trend over recent decades, but severe pulses of tree mortality in forests after droughts and heatwaves have also been extensively reported. These observations raise the question of to what extent the observed severe pulses of tree mortality induced by climate could affect overall vegetation greenness across spatial grains and temporal extents. To address this issue, here we analyse three satellite-based datasets of detrended growing-season normalized difference vegetation index (NDVIGS) with spatial resolutions ranging from 30 m to 8 km for 1,303 field-documented sites experiencing severe drought- or heat-induced tree-mortality events around the globe. We find that severe tree-mortality events have distinctive but localized imprints on vegetation greenness over annual timescales, which are obscured by broad-scale and long-term greening. Specifically, although anomalies in NDVIGS (ΔNDVI) are negative during tree-mortality years, this reduction diminishes at coarser spatial resolutions (that is, 250 m and 8 km). Notably, tree-mortality-induced reductions in NDVIGS (|ΔNDVI|) at 30-m resolution are negatively related to native plant species richness and forest height, whereas topographic heterogeneity is the major factor affecting ΔNDVI differences across various spatial grain sizes. Over time periods of a decade or longer, greening consistently dominates all spatial resolutions. The findings underscore the fundamental importance of spatio-temporal scales for cohesively understanding the effects of climate change on forest productivity and tree mortality under both gradual and abrupt changes.
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Mudança Climática , Florestas , Árvores , Árvores/crescimento & desenvolvimento , SecasRESUMO
Porcine epidemic diarrhea (PED) caused by the porcine epidemic diarrhea virus (PEDV) has caused huge losses in the swine industry worldwide. Glucosyltransferase Rab-like GTPase activator and myotubularin domain containing 4 (GRAMD4) is a proapoptotic protein, which replaced p53 inducing mitochondrial apoptosis. However, the relationship between GRAMD4 and PEDV has not been reported. Here, we aimed to investigate the potential role of GRAMD4 during PEDV infection. In this study, we used co-immunoprecipitation (co-IP) and mass spectrometry to identify GRAMD4 interaction with PEDV non-structural protein 6 (NSP6). Immunoprecipitation and laser confocal microscopy were utilized to demonstrate that GRAMD4 interacts with NSP6. NSP6 reduces GRAMD4 production through PERK and IRE1 pathway-mediated apoptosis. We demonstrated that overexpression of GRAMD4 effectively impaired the replication of PEDV, whereas knockdown of GRAMD4 facilitated the replication of PEDV. Overexpression of GRAMD4 increased GRP78, phosphorylated PERK (p-PERK), phosphorylated IRE1(p-IRE1) levels, promoted CHOP, phosphorylated JNK (p-JNK), Bax expression, caspase 9 and caspase 3 cleavage, and inhibited Bcl-2 production. Knockdown of GRAMD4 has the opposite effect. Finally, deletion of the GRAM domain of GRAMD4 cannot cause endoplasmic reticulum stress (ER stress)-mediated apoptosis and inhibit virus replication. In conclusion, these studies revealed the mechanism by which GRAMD4 was associated with ER stress and apoptosis regulating PEDV replication. NSP6 acted as a potential down-regulator of GRAMD4 and promoted the degradation of GRAMD4. GRAMD4 played a role in facilitating apoptosis and restricting virus replication, and the GRAM domain was required. These findings provided a reference for host-PEDV interactions and offered the possibility for PEDV decontamination and prevention.
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Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Animais , Suínos , Vírus da Diarreia Epidêmica Suína/fisiologia , Replicação Viral , Apoptose , Proteínas Serina-Treonina Quinases , Estresse do Retículo Endoplasmático , Infecções por Coronavirus/veterináriaRESUMO
Porcine epidemic diarrhea virus (PEDV) infection causes severe diarrhea, dehydration, and high mortality in sick pigs, causing huge economic losses to the pig industry. However, the relationship between cell communication network factor 1 (CCN1) and PEDV infection has not been reported. In this study, we showed that the expression of CCN1 was enhanced by PEDV infection, and we observed that PEDV promotes the CREB and AP-1 activation to promote CCN1 expression. The PKA and p38 inhibitors significantly suppress CCN1 expression, indicating that PEDV-induced CCN1 expression may be through PKA and p38 pathway. Further tests confirmed that CREB and AP-1 are regulated by PKA and p38, respectively. Overexpression of CCN1 decreased the replication of PEDV, whereas knockdown of CCN1 increased the replication of PEDV. We proved that the overexpression of CCN1 increased the phosphorylation level of p53, promoted the expresion of Bax and the cleavage of caspase 9 and caspase 3, and inhibited the production of Bcl-2. CCN1 knockdown decreased the phosphorylation level of p53, inhibited the production of Bax and the cleavage of caspase 9 and caspase 3, and promoted the expression of Bcl-2. The treatment of PFT-α (p53 inhibitor) significantly suppressed the expression of cleaved caspase 9 and caspase 3, leading to the decrease of apoptosis. Together, these studies showed that PEDV promotes the activation of CREB and AP-1 to increase the expression of CCN1. Overexpression of CCN1 promotes apoptosis by elevating p53 protein phosphorylation and inhibits PEDV replication, and knockdown of CCN1 inhibits apoptosis by decreasing p53 protein phosphorylation and promotes PEDV replication. Our study could provide some reference for the molecular mechanisms of PEDV-induced CCN1 induction and supply a new therapeutic target for PEDV.
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Porcine epidemic diarrhea (PED), caused by the porcine epidemic diarrhea virus (PEDV), has arisen huge economic losses to the swine industry worldwide. The Asp-Glu-Ala-Asp (DEAD)-box polypeptide 6 (DDX6), a DEAD-box RNA helicase family member, acts as a suppressor of autophagy, however, whether it participates in PEDV-induced autophagy remains unclear. Here, we aimed to investigate the potential role of DDX6 during PEDV infection. We found that DDX6 protein expression was down-regulated and mRNA expression was up-regulated in PEDV-infected cells. Overexpression of DDX6 effectively impaired PEDV replication, while knockdown of DDX6 facilitated viral replication. Overexpression of DDX6 facilitated the degradation of autophagy-related gene (ATG) mRNA and partially rescued the dephosphorylation of mammalian target of rapamycin (mTOR) by PEDV infection. We also found that PEDV-triggered endoplasmic reticulum (ER) stress reduced the protein level of DDX6, and conversely, silencing of DDX6 is necessary and sufficient to alleviate ER stress and cell apoptosis. In addition, the loss of RNA helicase activity on DDX6 lost the ability to suppress autophagy and failed to restrict PEDV replication. Taken together, these findings indicated a DDX6-based mechanism that associates ER stress with autophagy activation during PEDV infection. PEDV-triggered ER stress down-regulated the expression of DDX6 to induce autophagy by inhibiting degradation of ATGs and phosphorylation of mTOR signaling, which alleviates ER stress and Promotes cell survival rather than apoptosis. These findings provided new insight into the function of DDX6 in autophagy during PEDV infection and may serve as a therapeutic strategy for controlling PEDV infection.
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Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Animais , Autofagia , Chlorocebus aethiops , Infecções por Coronavirus/veterinária , RNA Helicases DEAD-box , Estresse do Retículo Endoplasmático , Mamíferos , Vírus da Diarreia Epidêmica Suína/genética , Suínos , Células VeroRESUMO
The growth of the economy in the tropics is faster than that in the rest of the world. However, whether this growth can have impacts on the environmental quality in the tropics is still a question. Here, we first introduce the terrestrial carbon sequestration capacity as an environmental indicator and then investigate the relationships between gross domestic product per capita, sectoral economies, and the terrestrial carbon sequestration capacity for different income countries in the tropics from 1995 to 2018. By using panel models, we find that there exists a significantly negative effect of the growth of gross domestic product per capita on terrestrial carbon sequestration capacity in the full panel and at low-income and lower middle-income levels but not at the upper middle-income level. The sectoral economies have different effects on the terrestrial carbon sequestration capacity at different income levels. Interestingly, the industrial sector dominates the degradation of the terrestrial carbon sequestration capacity in the lower middle-income countries; the agricultural sector exerts a significantly negative impact on the terrestrial carbon sequestration capacity at the low-income and upper middle-income levels, but largely offset by the growth of the service sector. These findings suggest that the balance between economic development and the natural environment is required for economic sustainability in the tropics.
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Corynebacterium pseudotuberculosis (C.pseudotuberculosis) is a zoonotic pathogen that can cause cheese lymphadenitis in goats. In order to obtain detailed information about the pathogenesis and host immune response of goats infected with C.pseudotuberculosis, we used tandem mass tag (TMT)-labeling proteomic analysis to detect differentially expressed proteins (DEPs) in dairy goats infected with C.pseudotuberculosis, and confirmed the altered proteins with western blot. A total of 6611 trusted proteins were identified, and 126 proteins were differentially abundant. Gene ontology (GO) analysis showed that all DEPs were annotated as biological processes, cell composition, and molecular functions. Biological processes mainly involve acute inflammation and immune response; cell components mainly involve extracellular areas and high-density lipoprotein particles; molecular functions are mainly antigen binding, ferric iron binding, and iron ion binding. KEGG analysis showed that a total of 102 pathways were significantly enriched, mainly lysosomes, phagosomes, and mineral absorption pathways. Our findings provided the relevant knowledge of spleen protein levels in goats infected with C.pseudotuberculosis and revealed the complex molecular pathways and immune response mechanisms in the process of C.pseudotuberculosis infection. SIGNIFICANCE: C.pseudotuberculosis is the most fatal infectious disease in dairy goats, causing huge economic losses. However, the molecular pathways and immune response mechanisms of C.pseudotuberculosis infection in goats remain unclear. Therefore, we conducted a comparative quantitative proteomics study on dairy goats infected with C.pseudotuberculosis. The results provide a basis for better understanding the complexity of C.pseudotuberculosis infection, reveal the complex molecular pathways and immune response mechanisms in C.pseudotuberculosis infection, and provide some clues for identifying potential therapeutic targets. This is the first report to show that C.pseudotuberculosis infection in dairy goats can disrupt the immune response mechanism and lead to massive immune cell death. The study provided new findings on the interaction between C.pseudotuberculosis and the host.
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Infecções por Corynebacterium , Proteômica , Animais , Infecções por Corynebacterium/veterinária , Cabras , Proteoma , BaçoRESUMO
Wastewater dissolved organic matter (DOM) from different processing stages of a sewage treatment plant in Xiamen was characterized using fluorescence and absorption spectroscopy. Parallel factor analysis modeling of excitation-emission matrix spectra revealed five fluorescent components occurring in sewage DOM: one protein-like (C1), three humic-like (C2, C4 and C5) and one xenobiotic-like (C3) components. During the aerated grit chamber and primary sedimentation tank stage, there was only a slight decrease in fluorescence intensity and the absorption coefficient at 350 nm (a350). During the second aeration stage, high concentration of protein-like and short-wavelength-excited humic-like components were significantly degraded accompanied by significant loss of DOC (80%) and a350 (30%), indicating that C1 and C2 were the dominant constituents of sewage DOM. As a result, long-wavelength-excited C4 and C5 became the dominant humic-like components and the DOM molecular size inferred from the variation of spectral slope S (300-650 nm) and specific absorption (a280/DOC) increased. Combination use of F(max) of C1 and the ratio of C1/C5, or a350 may provide a quantitative indication for the relative amount of raw or treated sewage in aquatic environment.