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Enterovirus 71 (EV71) is a significant causative agent of hand, foot, and mouth disease, with potential serious neurologic complications or fatal outcomes. The lack of effective treatments for EV71 infection is attributed to its elusive pathogenicity. Our study reveals that human plasmacytoid dendritic cells (pDCs), the main type I IFN-producing cells, selectively express scavenger receptor class B, member 2 (SCARB2) and P-selectin glycoprotein ligand 1 (PSGL-1), crucial cellular receptors for EV71. Some strains of EV71 can replicate within pDCs and stimulate IFN-α production. The activation of pDCs by EV71 is hindered by Abs to PSGL-1 and soluble PSGL-1, whereas Abs to SCARB2 and soluble SCARB2 have a less pronounced effect. Our data suggest that only strains binding to PSGL-1, more commonly found in severe cases, can replicate in pDCs and induce IFN-α secretion, highlighting the importance of PSGL-1 in these processes. Furthermore, IFN-α secretion by pDCs can be triggered by EV71 or UV-inactivated EV71 virions, indicating that productive infection is not necessary for pDC activation. These findings provide new insights into the interaction between EV71 and pDCs, suggesting that pDC activation could potentially mitigate the severity of EV71-related diseases.
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Células Dendríticas , Enterovirus Humano A , Interferon-alfa , Proteínas de Membrana Lisossomal , Glicoproteínas de Membrana , Células Dendríticas/imunologia , Células Dendríticas/virologia , Humanos , Enterovirus Humano A/imunologia , Enterovirus Humano A/fisiologia , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana Lisossomal/metabolismo , Proteínas de Membrana Lisossomal/imunologia , Interferon-alfa/metabolismo , Interferon-alfa/imunologia , Receptores Depuradores/metabolismo , Infecções por Enterovirus/imunologia , Infecções por Enterovirus/virologia , Replicação ViralRESUMO
As a plant-specific transcription factor, lateral organ boundaries domain (LBD) protein was reported to regulate plant growth and stress response, but the functional research of subfamily II genes is limited. SlMYC2, a master regulator of Jasmonic acid response, has been found to exhibit high expression levels in fruit and has been implicated in the regulation of fruit ripening and resistance to Botrytis. However, its role in fruit expansion remains unknown. In this study, we present evidence that a subfamily II member of LBD, namely SlLBD40, collaborates with SlMYC2 in the regulation of fruit expansion. Overexpression of SlLBD40 significantly promoted fruit growth by promoting mesocarp cell expansion, while knockout of SlLBD40 showed the opposite result. Similarly, SlMYC2 knockout resulted in a significant decrease in cell expansion within the fruit. Genetic analysis indicated that SlLBD40-mediated cell expansion depends on the expression of SlMYC2. SlLBD40 bound to the promoter of SlEXPA5, an expansin gene, but did not activate its expression directly. While, the co-expression of SlMYC2 and SlLBD40 significantly stimulated the activation of SlEXPA5, leading to an increase in fruit size. SlLBD40 interacted with SlMYC2 and enhanced the stability and abundance of SlMYC2. Furthermore, SlMYC2 directly targeted and activated the expression of SlLBD40, which is essential for SlLBD40-mediated fruit expansion. In summary, our research elucidates the role of the interaction between SlLBD40 and SlMYC2 in promoting cell expansion in tomato fruits, thus providing novel insights into the molecular genetics underlying fruit growth.
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Frutas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Solanum lycopersicum , Fatores de Transcrição , Solanum lycopersicum/genética , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/metabolismo , Frutas/genética , Frutas/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genéticaRESUMO
Drought is the most severe form of stress experienced by plants worldwide. Cucumber is a vegetable crop that requires a large amount of water throughout the growth period. In our previous study, we identified that overexpression of CsHSFA1d could improve cold tolerance and the content of endogenous jasmonic acid in cucumber seedlings. To explore the functional diversities of CsHSFA1d, we treat the transgenic plants under drought conditions. In this study, we found that the heat shock transcription factor HSFA1d (CsHSFA1d) could improve drought stress tolerance in cucumber. CsHSFA1d overexpression increased the expression levels of galactinol synthase (CsGolS3) and raffinose synthase (CsRS) genes, encoding the key enzymes for raffinose family oligosaccharide (RFO) biosynthesis. Furthermore, the lines overexpressing CsHSFA1d showed higher enzymatic activity of GolS and raffinose synthase to increase the content of RFO. Moreover, the CsHSFA1d-overexpression lines showed lower reactive oxygen species (ROS) accumulation and higher ROS-scavenging enzyme activity after drought treatment. The expressions of antioxidant genes CsPOD2, CsAPX1 and CsSOD1 were also upregulated in CsHSFA1d-overexpression lines. The expression levels of stress-responsive genes such as CsRD29A, CsLEA3 and CsP5CS1 were increased in CsHSFA1d-overexpression lines after drought treatment. We conclude that CsHSFA1d directly targets and regulates the expression of CsGolS3 and CsRS to promote the enzymatic activity and accumulation of RFO to increase the tolerance to drought stress. CsHSFA1d also improves ROS-scavenging enzyme activity and gene expression indirectly to reduce drought-induced ROS overaccumulation. This study therefore offers a new gene target to improve drought stress tolerance in cucumber and revealed the underlying mechanism by which CsHSFA1d functions in the drought stress by increasing the content of RFOs and scavenging the excessive accumulation of ROS.
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Cucumis sativus , Galactosiltransferases , Regulação da Expressão Gênica de Plantas , Oligossacarídeos , Proteínas de Plantas , Plantas Geneticamente Modificadas , Rafinose , Espécies Reativas de Oxigênio , Cucumis sativus/genética , Cucumis sativus/fisiologia , Cucumis sativus/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Rafinose/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Oligossacarídeos/metabolismo , Galactosiltransferases/metabolismo , Galactosiltransferases/genética , Secas , Fatores de Transcrição de Choque Térmico/metabolismo , Fatores de Transcrição de Choque Térmico/genética , Estresse Fisiológico/genéticaRESUMO
The quality of electrophysiological (EP) signals heavily relies on the electrode's contact with the skin. However, motion or exposure to water can easily destabilize this connection. In contrast to traditional methods of attaching electrodes to the skin surface, this study introduces a skin-integration strategy inspired by the skin's intergrown structure. A highly conductive and room-temperature curable composite composed of silver microflakes and polydimethylsiloxane (Ag/PDMS) is applied to the skin. Before curing, the PDMS oil partially diffuse into the stratum corneum (SC) layer of the skin. Upon curing, the composite solidifies into an electrode that seamlessly integrated with the skin, resembling a natural extension. This skin-integration strategy offers several advantages. It minimizes motion artifacts resulting from relative electrode-skin displacement, significantly reduces interface impedance (67% of commercial Ag/AgCl gel electrodes at 100 Hz) and withstands water flushes due to its hydrophobic nature. These advantages pave the way for promising advancements in EP signal recording, particularly during motion and underwater conditions.
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We propose what we believe to be a new single-beam three-axis spin exchange relaxation free (SERF) vector atomic magnetometer scheme based on coordinate system deflection. A theoretical model for the system response under arbitrary angle deflection was established for the first time, and the system response at different angles was simulated and analyzed. The simulation results show that the system response increases in the direction of the non-sensitive axis and decreases in the direction of the sensitive axis as the deflection angle increases, and the two responses tend to be the same when the angle is deflected to 45-degrees. Experimental measurements were carried out at a deflection angle of 45-degrees and the results showed that the sensitivity of the magnetometer was 55fT/Hz1/2 in the x1-axis, 38fT/Hz1/2 in the y1-axis and 60fT/Hz1/2 in the z1-axis. This single-beam magnetometer can be used to construct a miniaturized and low-cost weak magnetic sensor, which is expected to be used for vector measurement of biomagnetism.
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We report a single-beam synthetic gradiometer operated in the spin-exchange-relaxation free (SERF) regime, using the structure of two separate atomic vapor cells spaced 2â cm apart. To improve the capability of the gradiometer in suppressing the common-mode magnetic field noise, we are aiming at investigating the effects of the system parameters on the gradiometer common-mode rejection ratio (CMRR). The mathematical expression for the relationship between the gradiometer CMRR and the two variables including the linewidth ratio and the pumping factor ratio is constructed for the first time, to our knowledge. This means that the CMRR can be optimized by controlling the linewidth and the pumping factor, which is easy to implement in the operation process. As a result, a CMRR of 246 is achieved and a gradiometer sensitivity of 4.5â fT/cm/Hz1/2 is also measured. This method provides a theoretical and experimental basis for the automated operation of gradiometers, and the gradiometer system performance can be tuned to a desired state by simply controlling the linewidth and the incident light intensity.
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The polar Kerr effect and the closely related anomalous charge Hall effect are among the most distinguishing signatures of the superconducting state in Sr_{2}RuO_{4}, as well as in several other compounds. These effects are often thought to be derived from chiral superconducting pairing, and different mechanisms have been invoked for the explanation. However, the intrinsic mechanisms proposed previously often involve unrealistically strong interband Cooper pairing. We show in this Letter that, even without interband pairing, nonunitary superconducting states can support the intrinsic anomalous charge Hall effect, thanks to the quantum geometric properties of the Bloch electrons. The key here is to have a normal-state spin Hall effect, for which a nonzero spin-orbit coupling is essential. A finite charge Hall effect then naturally arises at the onset of a spin-polarized nonunitary superconducting pairing. It depends on both the spin polarization and the normal-state electron Berry curvature, the latter of which is the imaginary part of the quantum geometric tensor of the Bloch states. Applying our results to the weakly paired Sr_{2}RuO_{4} we conclude that, if the reported Kerr effect is of intrinsic origin, the superconducting state is most likely nonunitary and has odd parity. Our theory may be generalized to other superconductors that exhibit the polar Kerr effect.
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INTRODUCTION/AIMS: GNE myopathy is a rare autosomal recessive disorder caused by pathogenic variants in the GNE gene, which is essential for the sialic acid biosynthesis pathway. Although over 300 GNE variants have been reported, some patients remain undiagnosed with monoallelic pathogenic variants. This study aims to analyze the entire GNE genomic region to identify novel pathogenic variants. METHODS: Patients with clinically compatible GNE myopathy and monoallelic pathogenic variants in the GNE gene were enrolled. The other GNE pathogenic variant was verified using comprehensive methods including exon 2 quantitative polymerase chain reaction and nanopore long-read single-molecule sequencing (LRS). RESULTS: A deep intronic GNE variant, c.862+870C>T, was identified in nine patients from eight unrelated families. This variant generates a cryptic splice site, resulting in the activation of a novel pseudoexon between exons 5 and 6. It results in the insertion of an extra 146 nucleotides into the messengerRNA (mRNA), which is predicted to result in a truncated humanGNE1(hGNE1) protein. Peanut agglutininï¼PNAï¼ lectin staining of muscle tissues showed reduced sialylation of mucin O-glycans on sarcolemmal glycoproteins. Notably, a third of patients with the c.862+870C>T variant exhibited thrombocytopenia. A common core haplotype harboring the deep intronic GNE variant was found in all these patients. DISCUSSION: The transcript with pseudoexon activation potentially affects sialic acid biosynthesis via nonsense-mediated mRNA decay, or resulting in a truncated hGNE1 protein, which interferes with normal enzyme function. LRS is expected to be more frequently incorporated in genetic analysis given its efficacy in detecting hard-to-find pathogenic variants.
Assuntos
Éxons , Íntrons , Complexos Multienzimáticos , Trombocitopenia , Humanos , Masculino , Feminino , Complexos Multienzimáticos/genética , Éxons/genética , Íntrons/genética , Adulto , Trombocitopenia/genética , Miopatias Distais/genética , Adulto Jovem , Adolescente , Criança , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Linhagem , Pessoa de Meia-IdadeRESUMO
We first report a single-light-source orthogonally pumped triaxial atomic magnetometer with a double-cell structure. By using a beam splitter to equally allocate the pump beam, the proposed triaxial atomic magnetometer is responsive to magnetic fields in all three directions, and without sacrificing system sensitivity. The experimental results indicate that, the magnetometer achieves a sensitivity of 22â fT/Hz1/2 in x-direction with a 3-dB bandwidth of 22â Hz, a sensitivity of 23â fT/Hz1/2 in y-direction with a 3-dB bandwidth of 23â Hz, and a sensitivity of 21â fT/Hz1/2 in z-direction with a 3-dB bandwidth of 25â Hz. This magnetometer is useful for the applications that require the measurements of the three components of the magnetic field.
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Real-time sweat monitoring is vital for athletes in order to reflect their physical conditions, quantify their exercise loads, and evaluate their training results. Therefore, a multi-modal sweat sensing system with a patch-relay-host topology was developed, which consisted of a wireless sensor patch, a wireless data relay, and a host controller. The wireless sensor patch can monitor the lactate, glucose, K+, and Na+ concentrations in real-time. The data is forwarded via a wireless data relay through Near Field Communication (NFC) and Bluetooth Low Energy (BLE) technology and it is finally available on the host controller. Meanwhile, existing enzyme sensors in sweat-based wearable sports monitoring systems have limited sensitivities. To improve their sensitivities, this paper proposes a dual enzyme sensing optimization strategy and demonstrates Laser-Induced Graphene (LIG)-based sweat sensors decorated with Single-Walled Carbon Nanotubes (SWCNT). Manufacturing an entire LIG array takes less than one minute and costs about 0.11 yuan in materials, making it suitable for mass production. The in vitro test result showed sensitivities of 0.53 µA/mM and 3.9 µA/mM for lactate and glucose sensing, and 32.5 mV/decade and 33.2 mV/decade for K+ and Na+ sensing, respectively. To demonstrate the ability to characterize personal physical fitness, an ex vivo sweat analysis test was also performed. Overall, the high-sensitivity lactate enzyme sensor based on SWCNT/LIG can meet the requirements of sweat-based wearable sports monitoring systems.
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Grafite , Nanotubos de Carbono , Humanos , Suor , Ácido Láctico , Glucose , LasersRESUMO
Glutamate is excitotoxic to neurons. The entry of glutamine or glutamate from the blood into the brain is limited. To overcome this, branched-chain amino acids (BCAAs) catabolism replenishes the glutamate in brain cells. Branched-chain amino acid transaminase 1 (BCAT1) activity is silenced by epigenetic methylation in IDH mutant gliomas. However, glioblastomas (GBMs) express wild type IDH. Here, we investigated how oxidative stress promotes BCAAs' metabolism to maintain intracellular redox balance and, consequently, the rapid progression of GBMs. We found that reactive oxygen species (ROS) accumulation promoted the nuclear translocation of lactate dehydrogenase A (LDHA), which triggered DOT1L (disruptor of telomeric silencing 1-like)-mediated histone H3K79 hypermethylation and enhanced BCAA catabolism in GBM cells. Glutamate derived from BCAAs catabolism participates in antioxidant thioredoxin (TxN) production. The inhibition of BCAT1 decreased the tumorigenicity of GBM cells in orthotopically transplanted nude mice, and prolonged their survival time. In GBM samples, BCAT1 expression was negatively correlated with the overall survival time (OS) of patients. These findings highlight the role of the non-canonical enzyme activity of LDHA on BCAT1 expression, which links the two major metabolic pathways in GBMs. Glutamate produced by the catabolism of BCAAs was involved in complementary antioxidant TxN synthesis to balance the redox state in tumor cells and promote the progression of GBMs.
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Aminoácidos de Cadeia Ramificada , Glioblastoma , Animais , Camundongos , Aminoácidos de Cadeia Ramificada/metabolismo , Antioxidantes , Proliferação de Células , Glioblastoma/genética , Ácido Glutâmico , Lactato Desidrogenase 5 , Camundongos Nus , Tiorredoxinas , HumanosRESUMO
Initiation and progression of leaf senescence are triggered by various environmental stressors and phytohormones. Jasmonic acid (JA) and darkness accelerate leaf senescence in plants. However, the mechanisms that integrate these two factors to initiate and regulate leaf senescence have not been identified. Here, we report a transcriptional regulatory module centred on a novel tomato WRKY transcription factor, SlWRKY37, responsible for both JA- and dark-induced leaf senescence. The expression of SlWRKY37, together with SlMYC2, encoding a master transcription factor in JA signalling, was significantly induced by both methyl jasmonate (MeJA) and dark treatments. SlMYC2 binds directly to the promoter of SlWRKY37 to activate its expression. Knock out of SlWRKY37 inhibited JA- and dark-induced leaf senescence. Transcriptome analysis and biochemical experiments revealed SlWRKY53 and SlSGR1 (S. lycopersicum senescence-inducible chloroplast stay-green protein 1) as direct transcriptional targets of SlWRKY37 to control leaf senescence. Moreover, SlWRKY37 interacted with a VQ motif-containing protein SlVQ7, and the interaction improved the stability of SlWRKY37 and the transcriptional activation of downstream target genes. Our results reveal the physiological and molecular functions of SlWRKY37 in leaf senescence, and offer a target gene to retard leaf yellowing by reducing sensitivity to external senescence signals, such as JA and darkness.
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Solanum lycopersicum , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Senescência Vegetal , Regulação da Expressão Gênica de Plantas , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Folhas de Planta/metabolismoRESUMO
A novel electrochemically assisted cycloaddition process is proposed, in which highly efficient coupling of CO2 with styrene oxide (SO) can be achieved to form styrene carbonate (SC) as a high-value-added product. A series of Cu catalysts with different morphologies and chemical states were fabricated on carbon paper (CP) by using in-situ electrodeposition, and the sample with nano-dendrimer structure was found to exhibit a relatively high activity of 74.8 % SC yield with 92.7 % SO conversion under gentle reaction conditions, thus showing its potential for practical applications. The relatively high electrochemically active surface area and charge transfer ability of dendrimer-like Cu benefited the electrochemical reaction. In particular, the Cu2+ species that were formed inâ situ during the reaction played a vital role in enhancing the activity and selectivity of the proposed Cu/CP hybrid catalyst. Cu2+ atoms served as active sites that can not only electrochemically activate CO2 but also facilitate the ring opening of SO. Mechanistic analysis suggested that the reaction followed electrochemical and liquid-phase heterogeneous paths, which provide a new green and sustainable route for efficient utilization of CO2 resources for fine chemical electrosynthesis.
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One novel monoterpene rhamnoside (1) and 7 known monoterpenes (2-8) were isolated from the ethanol extract of Cynanchum atratum for the first time. Their structures were identified by comprehensive spectroscopic data analysis such as nuclear magnetic resonance, high-resolution electrospray ionization mass spectra, optical rotatory dispersion, and acid hydrolysis. In the subsequent antioxidant assay, compound 8 exhibited obvious 2,2-diphenyl-2-picrylhydrazyl hydrate radical scavenging activity.
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Cynanchum , Vincetoxicum , Antioxidantes/análise , Antioxidantes/farmacologia , Cynanchum/química , Monoterpenos , Raízes de Plantas/química , Vincetoxicum/químicaRESUMO
Overcoming lignocellulosic biomass recalcitrance, especially the cleavage of cross-linkages in lignin-carbohydrate complexes (LCCs) and lignin, is essential for both the carbon cycle and industrial biorefinery. Lytic polysaccharide monooxygenases (LPMOs) are copper-containing enzymes that play a key role in fungal polysaccharide oxidative degradation. Nevertheless, comprehensive analysis showed that LPMOs from a white-rot fungus, Pleurotus ostreatus, correlated well with the Fenton reaction and were involved in the degradation of recalcitrant nonpolysaccharide fractions in this research. Thus, LPMOs participated in the extracellular Fenton reaction by enhancing iron reduction in quinone redox cycling. A Fenton reaction system consisting of LPMOs, hydroquinone, and ferric iron can efficiently produce hydroxy radicals and then cleave LCCs or lignin linkages. This finding indicates that LPMOs are underestimated auxiliary enzymes in eliminating biomass recalcitrance.
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Lignina , Pleurotus , Lignina/metabolismo , Oxigenases de Função Mista/metabolismo , Estresse Oxidativo , Pleurotus/metabolismo , PolissacarídeosRESUMO
Seneca Valley virus (SVV) has been identified as the causative agent of SVV-associated vesicular disease (SAVD). To investigate the pathogenicity of two newly isolated SVV strains (GD-S5/2018 and GD04/2017) in China, experimental infections of pigs were performed. In pig experiments, both SVV strains successfully infected all animals, evidenced by presence of virus shedding and robust protective antibody responses. SVV GD-S5/2018 infection resulted in characteristic clinical signs, and ulcerative lesions on the tongue and gums. However, SVV GD04/2017 did not cause any clinical symptoms except depression in pigs during the experiment. Taken together, these results demonstrate that SVV GD-S5/2018 is a virulent strain for pigs, whereas SVV GD04/2017 is nearly avirulent. The established animal models for SVV infection will be utilized to dissect the immunity and pathogenesis, and develop vaccines and antivirals.
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Infecções por Picornaviridae/veterinária , Picornaviridae/patogenicidade , Doença Vesicular Suína/patologia , Doença Vesicular Suína/virologia , Animais , China , Picornaviridae/isolamento & purificação , Infecções por Picornaviridae/patologia , Infecções por Picornaviridae/virologia , Suínos , VirulênciaRESUMO
Fungi can use n-hexadecane (HXD) as a sole carbon source. But the mechanism of HXD degradation remains unclear. This work mainly aimed to study the degradation of HXD by Aspergillus sp. RFC-1 obtained from oil-contaminated soil. The HXD content, medium acidification and presence of hexadecanoic acid in the medium were determined by gas chromatography-mass spectrometry, and fungal growth was observed. Enzyme and gene expression assays suggested the involvement of an alkane hydroxylase, an alcohol dehydrogenase, and a P450 enzyme system in HXD degradation. A biosurfactant produced by the strain RFC-1 was also characterized. During 10 days of incubation, 86.3% of HXD was degraded by RFC-1. The highest activities of alkane hydroxylase (125.4⯵molâ¯mg-1 protein) and alcohol dehydrogenase (12.5⯵molâ¯mg-1 proteins) were recorded. The expression level of cytochrome P450 gene associated with oxidation was induced (from 0.94-fold to 5.45-fold) under the HXD condition by Real-time PCR analysis. In addition, HXD accumulated in inclusion bodies of RFC-1with the maximum of 5.1â¯gâ¯L-1. Results of blood agar plate and thin-layer chromatography analysis showed RFC-1 released high lipid and emulsification activity in the fungal culture. Induced cell surface hydrophobicity and reduced surface tension also indicated the RFC-1-mediated biosurfactant production, which facilitated the HXD degradation and supported the degradation process.
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Alcanos/metabolismo , Aspergillus/metabolismo , Biodegradação Ambiental , Álcool Desidrogenase/metabolismo , Citocromo P-450 CYP4A/metabolismo , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Varredura , Espectroscopia de Infravermelho com Transformada de Fourier , Tensoativos/metabolismoRESUMO
Scavenger receptor class B, member 2 (SCARB2) is essential for endosome biogenesis and reorganization and serves as a receptor for both ß-glucocerebrosidase and enterovirus 71. However, little is known about its function in innate immune cells. In this study, we show that, among human peripheral blood cells, SCARB2 is most highly expressed in plasmacytoid dendritic cells (pDCs), and its expression is further upregulated by CpG oligodeoxynucleotide stimulation. Knockdown of SCARB2 in pDC cell line GEN2.2 dramatically reduces CpG-induced type I IFN production. Detailed studies reveal that SCARB2 localizes in late endosome/lysosome of pDCs, and knockdown of SCARB2 does not affect CpG oligodeoxynucleotide uptake but results in the retention of TLR9 in the endoplasmic reticulum and an impaired nuclear translocation of IFN regulatory factor 7. The IFN-I production by TLR7 ligand stimulation is also impaired by SCARB2 knockdown. However, SCARB2 is not essential for influenza virus or HSV-induced IFN-I production. These findings suggest that SCARB2 regulates TLR9-dependent IFN-I production of pDCs by mediating endosomal translocation of TLR9 and nuclear translocation of IFN regulatory factor 7.
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Células Dendríticas/imunologia , Fator Regulador 7 de Interferon/metabolismo , Interferon Tipo I/biossíntese , Proteínas de Membrana Lisossomal/imunologia , Receptores Depuradores/imunologia , Receptor Toll-Like 9/metabolismo , Western Blotting , Células Cultivadas , Células Dendríticas/metabolismo , Endossomos/metabolismo , Citometria de Fluxo , Imunofluorescência , Humanos , Proteínas de Membrana Lisossomal/metabolismo , Transporte Proteico/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Receptores Depuradores/metabolismoRESUMO
Atypical porcine reproductive and respiratory syndrome (PRRS), which is caused by the Chinese highly pathogenic PRRS virus (HP-PRRSV), has resulted in large economic loss to the swine industry since its outbreak in 2006. However, to date, the region(s) within the viral genome that are related to the fatal virulence of HP-PRRSV remain unknown. In the present study, we generated a series of full-length infectious cDNA clones with swapped coding regions between the highly pathogenic RvJXwn and low pathogenic RvHB-1/3.9. Next, the in vitro and in vivo replication and pathogenicity for piglets of the rescued chimeric viruses were systematically analyzed and compared with their backbone viruses. First, we swapped the regions including the 5'UTR+ORF1a, ORF1b, and structural proteins (SPs)-coding region between the two viruses and demonstrated that the nonstructural protein-coding region, ORF1b, is directly related to the fatal virulence and increased replication efficiency of HP-PRRSV both in vitro and in vivo. Furthermore, we substituted the nonstructural protein (Nsp) 9-, Nsp10-, Nsp11- and Nsp12-coding regions separately; or Nsp9- and Nsp10-coding regions together; or Nsp9-, Nsp10- and Nsp11-coding regions simultaneously between the two viruses. Our results indicated that the HP-PRRSV Nsp9- and Nsp10-coding regions together are closely related to the replication efficiency in vitro and in vivo and are related to the increased pathogenicity and fatal virulence for piglets. Our findings suggest that Nsp9 and Nsp10 together contribute to the fatal virulence of HP-PRRSV emerging in China, helping to elucidate the pathogenesis of this virus.
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Síndrome Respiratória e Reprodutiva Suína/imunologia , Vírus da Síndrome Respiratória e Reprodutiva Suína , Proteínas de Ligação a RNA/imunologia , Proteínas Virais/imunologia , Fatores de Virulência/imunologia , Replicação Viral/imunologia , Animais , Linhagem Celular , Cricetinae , Síndrome Respiratória e Reprodutiva Suína/genética , Síndrome Respiratória e Reprodutiva Suína/patologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/patogenicidade , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Proteínas de Ligação a RNA/genética , Suínos , Proteínas Virais/genética , Fatores de Virulência/genéticaRESUMO
Agriculture is a significant source of carbon emissions, which have a substantial environmental impact. The digital economy plays a vital role in mitigating these emissions through innovative digital solutions. As a leading agricultural nation, China faces substantial pressure to reduce its agricultural carbon emissions(ACE). This paper aims to thoroughly examine the relationship between the growth of the rural digital economy and ACE. To achieve this, we utilize an extensive panel dataset covering China's provinces from 2011 to 2020, analyzing the dynamic and spatial effects of digital economy development on ACE. The key findings of this research are as follows: (1) The rapid expansion of the digital economy significantly reduces ACE. (2) The impact of digital economic development on lowering ACE varies spatially, with a clear progression from eastern to western regions. (3) The digital economy helps reduce ACE through three specific channels: fostering technological innovation, enhancing scale efficiency management, and providing agricultural financial incentives. Based on these findings, this study proposes policy recommendations to improve digital infrastructure, promote balanced regional development in the digital economy, and optimize the management of agricultural science and technology. These policy insights aim to transform agriculture and achieve the goal of reducing ACE, thereby contributing to broader environmental sustainability.