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The perceived position of a moving object in vision entails an accumulation of neural signals over space and time. Due to neural signal transmission delays, the visual system cannot acquire immediate information about the moving object's position. Although physiological and psychophysical studies on the flash-lag effect (FLE), a moving object is perceived ahead of a flash even when they are aligned at the same location, have shown that the visual system develops the mechanisms of predicting the object's location to compensate for the neural delays, the neural mechanisms of motion-induced location prediction are not still understood well. Here, we investigated the role of neural activity changes in areas MT+ (specialized for motion processing) and the potential contralateral processing preference of MT+ in modulating the FLE. Using transcranial direct current stimulations (tDCS) over the left and right MT+ between pre- and posttests of the FLE in different motion directions, we measured the effects of tDCS on the FLE. The results found that anodal and cathodal tDCS enhanced and reduced the FLE with the moving object heading to but not deviating from the side of the brain stimulated, respectively, compared with sham tDCS. These findings suggest a causal role of area MT+ in motion-induced location prediction, which may involve the integration of position information.NEW & NOTEWORTHY Perceived positions of moving objects are related to neural activities in areas MT+. We demonstrate that tDCS over areas MT+ can modulate the FLE, and further anodal and cathodal tDCS facilitated and inhibited the FLE with a moving object heading to but not deviating from the side of the brain stimulated, respectively. These findings suggest a causal role of area MT+ in motion-induced location prediction and contribute to understanding the neural mechanism of the FLE.
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Percepção de Movimento , Estimulação Transcraniana por Corrente Contínua , Encéfalo , Eletrodos , Inibição Psicológica , Percepção de Movimento/fisiologiaRESUMO
The nuclear export protein (NEP) serves multiple functions in the life cycle of influenza A virus (IAV). Identifying novel host proteins that interact with NEP and understanding their functions in IAV replication are of great interest. In this study, we screened and confirmed the direct interaction of G protein pathway suppressor 2 (GPS2) with NEP through a yeast two-hybrid screening assay and glutathione S-transferase-pulldown and co-immunoprecipitation assays. Knockdown or knockout of GPS2 enhanced IAV titers, whereas overexpression of GPS2 impaired IAV replication, demonstrating that GPS2 acted as a negative host factor in IAV replication. Meanwhile, GPS2 inhibited viral RNA synthesis by reducing the assembly of IAV polymerase. Interestingly, IAV NEP interacted with GPS2 and mediated its nuclear export, thereby activated the degradation of GPS2. Thus, NEP-GPS2 interaction weakened the inhibition of GPS2 to viral polymerase activity and benefited virus replication. Overall, this study identified the novel NEP-binding host partner GPS2 as a critical host factor to participate in IAV replication. These findings provided novel insights into the interactions between IAV and host cells, revealing a new function for GPS2 during IAV replication.Importance: NEP is proposed to play multiple biologically important roles in the life cycle of IAV, which largely relies on host factors by interaction. Our study demonstrated that GPS2 could reduce the interaction between PB1 and PB2 and interfere with vRNP assembly. Thus, GPS2 inhibited the RNA synthesis of IAV and negatively regulated its replication. Importantly, IAV NEP interacted with GPS2 and mediated the nuclear export of GPS2, thereby activated the degradation of GPS2. Thus, NEP-GPS2 interaction weakened the inhibition of GPS2 to viral polymerase activity and benefited virus replication.
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Age is a risk factor for coronavirus disease 2019 (COVID-19) associated morbidity and mortality in humans; hence, in this study, we compared the course of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection in young and aged BALB/c mice. We found that SARS-CoV-2 isolates replicated in the respiratory tracts of 12-month-old (aged) mice and caused pathological features of pneumonia upon intranasal infection. In contrast, rapid viral clearance was observed 5 days following infection in 2-month-old (young) mice with no evidence of pathological changes in the lungs. Infection with SARS-CoV-2 elicited significantly upregulated production of cytokines, especially interleukin 6 and interferon gamma, in aged mice; whereas this response was much weaker in young mice. Subsequent challenge of infected aged BALB/c mice with SARS-CoV-2 resulted in neutralized antibody responses, a significantly reduced viral burden in the lungs, and inflammation mitigation. Deep sequencing showed a panel of mutations potentially associated with the enhanced infection in aged BALB/c mice, such as the Q498H mutations which are located at the receptor binding domain (RBD) of the spike (S) protein. We further found that the isolates can not only multiply in the respiratory tract of mice but also cause disease in aged mice. Overall, viral replication and rapid adaption in aged BALB/c mice were associated with pneumonia, confirming that the age-related susceptibility to SARS-CoV-2 in mice resembled that in humans.ImportanceAged BALB/c model are in use as a model of disease caused by SARS-CoV-2. Our research demonstrated SARS-CoV-2 can rapidly adapt in aged BALB/c mice through causing mutations at the RBD of the S protein. Moreover, SARS-CoV-2-infected aged BALB/c mice indicated that alveolar damage, interstitial pneumonia, and inflammatory immune responses were similar to the clinical manifestations of human infections. Therefore, our aged BALB/c challenge model will be useful for further understanding the pathogenesis of SARS-CoV-2 and for testing vaccines and antiviral agents.
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As a stereo odor cue, internostril odor influx could help us in many spatial tasks, including localization and navigation. Studies have also revealed that this benefit could be modulated by the asymmetric concentrations of both influxes (left nose vs right nose). The interaction between olfaction and vision, such as in object recognition and visual direction judgment, has been documented; however, little has been revealed about the impact of odor cues on sound localization. Here we adopted the ventriloquist paradigm in auditory-odor interactions and investigated sound localization with the concurrent unilateral odor influx. Specifically, we teased apart both the "nature" of the odors (pure olfactory stimulus vs. mixed olfactory/trigeminal stimulus) and the location of influx (left nose vs. right nose) and examined sound localization with the method of constant stimuli. Forty-one participants, who passed the Chinese Smell Identification Test, perceived sounds with different azimuths (0°, 5°, 10°, and 20° unilaterally deflected from the sagittal plane by head-related transfer function) and performed sound localization (leftward or rightward) tasks under concurrent, different unilateral odor influxes (10% v/v phenylethyl alcohol, PEA, as pure olfactory stimulus, 1% m/v menthol as mixed olfactory/trigeminal stimulus, and propylene glycol as the control). Meanwhile, they reported confidence levels of the judgments. Results suggested that unilateral PEA influx did not affect human sound localization judgments. However, unilateral menthol influx systematically biased the perceived sound localization, shifting toward the odor source. Our study provides evidence that unilateral odor influx could bias perceived sound localization only when the odor activates the trigeminal nerves.
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Odorantes , Localização de Som , Humanos , Mentol , Olfato/fisiologia , Nervo Trigêmeo/fisiologiaRESUMO
Perovskite nanocrystals (NCs) have emerged as attractive gain materials for solution-processed microlasers. Despite the recent surge of reports in this field, it is still challenging to develop low-cost perovskite NC-based microlasers with high performance. Herein, we demonstrate low-threshold, spectrally tunable lasing from ensembles of CsPbBr3NCs deposited on silica microspheres. Multiple whispering-gallery-mode lasing is achieved from individual NC/microspheres with a low threshold of â¼3.1µJ cm-2and cavity quality factor of â¼1193. Through time-resolved photoluminescence measurements, electron-hole plasma recombination is elucidated as the lasing mechanism. By tuning the microsphere diameter, the desirable single-mode lasing is successfully achieved. Remarkably, the CsPbBr3NCs display durable room-temperature lasing under â¼107shots of pulsed laser excitation, substantially exceeding the stability of conventional colloidal NCs. These CsPbBr3NC-based microlasers can be potentially useful in photonic applications.
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Photoelectrochemical (PEC) water splitting is a potential solution for a low-carbon society and clean energy storage due to its ability to produce hydrogen and oxygen. However, the slow oxidation half-reaction of the process has limited its overall efficacy, necessitating the development of an efficient photoanode. Colloidal CsPbBr3 nanocrystals (NCs) have been identified as promising candidates due to their high light absorption and valence band position. However, the presence of the electrical insulator, long-chain oleate molecules, on the surface of the CsPbBr3 NCs has hindered efficient charge carrier separation and transport. To solve this problem, short-chain 1,2-ethanedithiol (EDT) ligands were used to replace the oleate ligands on the surface of the CsPbBr3 NCs through a solid-state ligand exchange method. This resulted in a reduction of the nanocrystal spacing and a cross-linking reaction, which improved the photogenerated carrier separation and transport while still passivating the dangling bonds on the CsPbBr3 NC surface. Ultimately, this led to a remarkable photocurrent density of 3.34 mA cm-2 (1.23 VRHE), which was 5.2 times higher than that of the pristine oleate-CsPbBr3 NC (0.64 mA cm-2)-based device. This work presents an efficient way of developing inorganic lead halide perovskite colloidal nanocrystal-based photoanodes through surface ligand engineering.
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Electrocatalytic two-electron oxygen reduction (2e- ORR) to hydrogen peroxide (H2 O2 ) is attracting broad interest in diversified areas including paper manufacturing, wastewater treatment, production of liquid fuels, and public sanitation. Current efforts focus on researching low-cost, large-scale, and sustainable electrocatalysts with high activity and selectivity. Here a large-scale H2 O2 electrocatalysts based on metal-free carbon fibers with a fluorine and sulfur dual-doping strategy is engineered. Optimized samples yield with a high onset potential of 0.814 V versus reversible hydrogen electrode (RHE), an almost ideal 2e- pathway selectivity of 99.1%, outperforming most of the recently reported carbon-based or metal-based electrocatalysts. First principle theoretical computations and experiments demonstrate that the intermolecular charge transfer coupled with electron spin redistribution from fluorine and sulfur dual-doping is the crucial factor contributing to the enhanced performances in 2e- ORR. This work opens the door to the design and implementation of scalable, earth-abundant, highly selective electrocatalysts for H2 O2 production and other catalytic fields of industrial interest.
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BACKGROUND: Pain is known to interrupt attentional performance selectively. In a previous study, we showed that the interruptive effect of thermal pain on attention could persist up to 1500 ms after painful stimulus offset, but whether the pain modality affects this subsequent interruptive effect remains unclear. METHODS: The present study was conducted to determine the time course of the interruptive effect of electrically induced pain on orienting and executive attention using various intervals between electric stimulation and attentional tasks (0, 250, 500, 750, 1000, 1250 and 1500 ms) and three study groups (pain, non-pain and control). We performed two separate experiments in which participants performed a spatial cue task (Experiment 1) and the Stroop task (Experiment 2). Participants in the pain and non-pain groups received brief electric somatosensory stimulation, and those in the control group received no physical stimulus. We compared the performance of the three groups under the interstimulus interval (ISI) conditions. RESULTS: The impairment of orienting attention prevailed under the first six ISI conditions in the pain and non-pain groups (F2, 63 = 5.72, p < 0.01); executive attention was not affected (F1,66 = 1.64, p = 0.20), confirming the persistence of the interruptive effect after stimulus offset. CONCLUSIONS: This study demonstrated the interruptive effect of somatic stimulation on subsequent orienting attention performance, with no effect on executive attention. These findings suggest that pain has differential effects on the components of attention, depending on its modality and salience. SIGNIFICANCE: This study confirmed that pain had a selective subsequent interruptive effect on attention and found that the time course of the interruption depended on the modality of pain and the component of attention.
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Atenção , Dor , Atenção/fisiologia , Sinais (Psicologia) , Humanos , Medição da Dor , Tempo de Reação/fisiologiaRESUMO
Interoception is the sensation of the physiological state inside one's body. Growing evidence suggests that visual feedback of interoception improves body self-consciousness (BSC) and reduces pain perception among patients with chronic pain. However, whether the integration of exteroception and interoception influences pain processing in healthy individuals remains largely unknown. To examine this question, we combined the rubber hand illusion (RHI) paradigm with visualized interoception -flashing of an LED light on the rubber hand synchronously or asynchronously with participants' real-time heartbeats. Under these conditions, we tested pain thresholds and corresponding event-related potentials. The interoceptive visual feedback inhibited the P2 component of pain, and the RHI inhibited pre-stimulus alpha-band brain activity. BSC had no significant effect on the processing of pain. These findings demonstrate that interoceptive signals with visual feedback inhibit pain processing, and that this psychophysiological process is largely independent of reported self-consciousness, in healthy individuals.
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Dor Aguda , Ilusões , Interocepção , Imagem Corporal , Mãos/fisiologia , Humanos , Ilusões/fisiologia , Interocepção/fisiologia , Percepção Visual/fisiologiaRESUMO
The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis and economic losses. Although several cases of cats and dogs infected with SARS-CoV-2 have been reported during this outbreak, the prevalence of SARS-CoV-2 in dog and its transmission among other companion animals are still unknown. Here, we report an extensive serological study of SARS-CoV-2 infection in dogs in Wuhan and analyse the infection rates at different stages of the pandemic outbreak. A total of 946 dogs serum samples were collected from Wuhan, of which 36 samples were obtained prior to the pandemic outbreak. Indirect enzyme-linked immunosorbent assay (ELISA) showed that 16 sera collected during the outbreak were detected as positive through the receptor-binding domain (RBD) of SARS-CoV-2. Of these 16 sera, 10 exhibited measurable SARS-CoV-2-specific neutralizing antibodies whose titres ranged from 1/20 to 1/180. No serological cross-reactivity was detected between SARS-CoV-2 and canine coronavirus (CCV). Furthermore, with the effective control of the outbreak, a decrease in the SARS-CoV-2 seropositive dog number was observed. Our results suggest that SARS-CoV-2 has infected companion dogs during the outbreak, and that COVID-19 patient families have a higher risk of dog infection. Our findings deepen our understanding of the infection of SARS-CoV-2 in dogs and provide an important reference for prevention of COVID-19.
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COVID-19 , Doenças do Gato , Doenças do Cão , Animais , Anticorpos Antivirais , COVID-19/epidemiologia , COVID-19/veterinária , Gatos , Doenças do Cão/epidemiologia , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Humanos , Pandemias , SARS-CoV-2RESUMO
Influenza A viruses are serious zoonotic pathogens that continuously cause pandemics in several animal hosts, including birds, pigs, and humans. Indole derivatives containing an indole core framework have been extensively studied and developed to prevent and/or treat viral infection. This study evaluated the anti-influenza activity of several indole derivatives, including 3-indoleacetonitrile, indole-3-carboxaldehyde, 3-carboxyindole, and gramine, in A549 and MDCK cells. Among these compounds, 3-indoleacetonitrile exerts profound antiviral activity against a broad spectrum of influenza A viruses, as tested in A549 cells. Importantly, in a mouse model, 3-indoleacetonitrile with a non-toxic concentration of 20 mg/kg effectively reduced the mortality and weight loss, diminished lung virus titers, and alleviated lung lesions of mice lethally challenged with A/duck/Hubei/WH18/2015 H5N6 and A/Puerto Rico/8/1934 H1N1 influenza A viruses. The antiviral properties enable the potential use of 3-indoleacetonitrile for the treatment of IAV infection.
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Antivirais/farmacologia , Indóis/farmacologia , Indóis/uso terapêutico , Vírus da Influenza A/efeitos dos fármacos , Infecções por Orthomyxoviridae/tratamento farmacológico , Células A549 , Animais , Antivirais/uso terapêutico , Antivirais/toxicidade , Cães , Feminino , Humanos , Indóis/toxicidade , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/fisiologia , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Virus da Influenza A Subtipo H5N1/fisiologia , Vírus da Influenza A/fisiologia , Pulmão/patologia , Pulmão/virologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Sulfetos/farmacologia , Carga Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
The influenza A virus (IAV) infection is usually restricted to the respiratory tract and only rarely enters the central nervous system (CNS) and causes neurological symptoms. However, the roles of host factors involved in IAV infection in the CNS remain largely undetermined. Therefore, we aimed to characterize the host responses to IAV infection in the brain. We isolated a strain of IAV H5N6, which is neurotoxic and highly pathogenic to mice. High-throughput RNA sequencing (RNA-seq) revealed 240 differentially expressed genes in IAV-infected brains. Among the significantly downregulated genes, we focused on the gene encoding progesterone receptor membrane component-1 (PGRMC1) and observed that IAV H5N6 infection clearly inhibited PGRMC1 in both neuroblastoma and glioma cells. Furthermore, treatment with AG205, a PGRMC1-specific inhibitor, or PGRMC1 knockout promoted H5N6 multiplication in vitro, while overexpression of PGRMC1 resulted in opposite effects. Furthermore, AG205 treatment or PGRMC1 knockout significantly inhibited the retinoic acid-inducible gene I (RIG-I)-mediated interferon beta (IFN-ß) signaling pathway and reduced the levels of several antiviral proteins (Mx1 and ISG15). In addition, PGRMC1-mediated regulation of IFN signaling relied on inhibition of the expression and ubiquitination of RIG-I. The loss of PGRMC1 leads to an increased susceptibility of mice (brain and lung) to influenza A virus infection. Conclusively, our results show for the first time that IAV H5N6 downregulates PGRMC1 expression to contribute to virus proliferation by inhibiting RIG-I-mediated IFN-ß production in the brain. These findings may offer new insights regarding the interplay between IAV and host factors that may impact IAV pathogenicity in the brain. IMPORTANCE Central nervous system (CNS) disease is one of the most common extra-respiratory tract complications of influenza A virus (IAV) infections. However, there is still little knowledge about IAV regulating host responses in brain. In this study, we identified progesterone receptor membrane component-1 (PGRMC1) as a novel host factor involved in the replication and propagation of IAV H5N6 in the host brain. We also observed that PGRMC1 antagonism was required for viral evasion from the host immune response during IAV infection via inhibition of the retinoic acid-inducible gene I (RIG-I)-mediated interferon beta (IFN-ß) signaling pathway and downstream antiviral gene expression. This study revealed a newly identified regulatory mechanism used by IAV H5N6 to ensure its life cycle in the CNS.
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Antivirais/farmacologia , Sistema Nervoso Central/metabolismo , Proteínas de Membrana/metabolismo , Receptores de Progesterona/metabolismo , Animais , Feminino , Interações Hospedeiro-Patógeno , Humanos , Vírus da Influenza A , Influenza Humana , Pulmão/virologia , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Infecções por Orthomyxoviridae , Receptores de Progesterona/genética , Transcriptoma , Replicação ViralRESUMO
BACKGROUND: An ideal animal model to study SARS-coronavirus 2 (SARS-CoV-2) pathogenesis and evaluate therapies and vaccines should reproduce SARS-CoV-2 infection and recapitulate lung disease like those seen in humans. The angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV-2, but mice are resistant to the infection because their ACE2 is incompatible with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein . METHODS: SARS-CoV-2 was passaged in BALB/c mice to obtain mouse-adapted virus strain. Complete genome deep sequencing of different generations of viruses was performed to characterize the dynamics of the adaptive mutations in SARS-CoV-2. Indirect immunofluorescence analysis and Biolayer interferometry experiments determined the binding affinity of mouse-adapted SARS-CoV-2 WBP-1 RBD to mouse ACE2 and human ACE2. Finally, we tested whether TLR7/8 agonist Resiquimod (R848) could also inhibit the replication of WBP-1 in the mouse model. FINDINGS: The mouse-adapted strain WBP-1 showed increased infectivity in BALB/c mice and led to severe interstitial pneumonia. We characterized the dynamics of the adaptive mutations in SARS-CoV-2 and demonstrated that Q493K and Q498H in RBD significantly increased its binding affinity towards mouse ACE2. Additionally, the study tentatively found that the TLR7/8 agonist Resiquimod was able to protect mice against WBP-1 challenge. Therefore, this mouse-adapted strain is a useful tool to investigate COVID-19 and develop new therapies. INTERPRETATION: We found for the first time that the Q493K and Q498H mutations in the RBD of WBP-1 enhanced its interactive affinities with mACE2. The mouse-adapted SARS-CoV-2 provides a valuable tool for the evaluation of novel antiviral and vaccine strategies. This study also tentatively verified the antiviral activity of TLR7/8 agonist Resiquimod against SARS-CoV-2 in vitro and in vivo. FUNDING: This research was funded by the National Key Research and Development Program of China (2020YFC0845600) and Emergency Science and Technology Project of Hubei Province (2020FCA046) and Robert A. Welch Foundation (C-1565).
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Substituição de Aminoácidos , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/virologia , Imidazóis/administração & dosagem , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/metabolismo , Adaptação Fisiológica , Animais , Sítios de Ligação , COVID-19/metabolismo , COVID-19/prevenção & controle , Células CACO-2 , Chlorocebus aethiops , Modelos Animais de Doenças , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imidazóis/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , SARS-CoV-2/genética , Inoculações Seriadas , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Células Vero , Replicação Viral/efeitos dos fármacos , Sequenciamento Completo do GenomaRESUMO
Although pain has been shown to affect attentional performance, little is known about the time course of attention interruption after pain stimulus perception. The present study examined the time course of the effects of transient heat pain stimulation on 2 components of attention. Three groups of subjects performed attention tasks under pain, warmth, and no-stimulation control conditions, respectively. The pain and warmth groups received brief physical stimulation. Attention tasks were presented 0 ms, 250 ms, 750 ms, or 1500 ms after the end of stimulation. The 2 attention tasks, namely the spatial cue task (Experiment 1, Nâ¯=â¯92) and a Stroop task (Experiment 2, Nâ¯=â¯86), were conducted separately. In Experiment 1, attentional orientation of the pain and warmth groups was significantly impaired for at least 1.5 seconds after the physical stimulation had ended. Interestingly, this effect lasted longer for the warmth group than for the pain group. In Experiment 2, pain stimulation had no effect on executive attention at any time. We concluded that attentional orientation is selectively disrupted by both pain and warmth stimuli, but recovers earlier from pain. PERSPECTIVE: This article is concerned with the subsequent interruptive effect of pain on attentional orientation and executive attention by using the spatial cue task and the Stroop task, respectively. These measures offer options for investigating the time course of attention interruption after transient pain stimulation.
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Atenção/fisiologia , Temperatura Alta/efeitos adversos , Percepção da Dor/fisiologia , Dor/psicologia , Tempo de Reação/fisiologia , Comportamento Espacial/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Dor/diagnóstico , Estimulação Luminosa/métodos , Distribuição Aleatória , Adulto JovemRESUMO
Influenza virus infection can alter the composition of the gut microbiota, while its pathogenicity can, in turn, be highly influenced by the gut microbiota. However, the details underlying these associations remain to be determined. The H7N9 influenza virus is an emerging zoonotic pathogen which has caused the death of 616 humans and has incurred huge losses in the poultry industry. Here, we investigated the effects of infection with highly pathogenic H7N9 on gut microbiota and determined potential anti-influenza microbes. 16S rRNA sequencing results show that H7N9 infection alters the mouse gut microbiota by promoting the growth of Akkermansia, Ruminococcus 1, and Ruminococcaceae UCG-010, and reducing the abundance of Rikenellaceae RC9 gut group and Lachnoclostridium. Although the abundance of Akkermansia muciniphila is positively related to H7N9 infection, the oral administration of cultures, especially of pasteurized A. muciniphila, can significantly reduce weight loss and mortality caused by H7N9 infection in mice. Furthermore, oral administration of live or pasteurized A. muciniphila significantly reduces pulmonary viral titers and the levels IL-1ß and IL-6 but enhances the levels of IFN-ß, IFN-γ, and IL-10 in H7N9-infected mice, suggesting that the anti-influenza role of A. muciniphila is due to its anti-inflammatory and immunoregulatory properties. Taken together, we showed that the changes in the gut microbiota are associated with H7N9 infection and demonstrated the anti-influenza role of A. muciniphila, which enriches current knowledge about how specific gut bacterial strains protect against influenza infection and suggests a potential anti-influenza probiotic.
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Avian influenza A (H7N9) viruses emerged in China in 2013 and caused a zoonotic disease associated with a high case-fatality ratio of more than 30%. Transcriptional profiles obtained using animal models reveal host responses to the disease, thereby providing insights into disease pathogenesis. Therefore, we aimed to characterize the host responses of the H7N9 virus infected-mouse lungs in this study. First, we isolated an avian-originated H7N9 strain, which was shown to be highly pathogenic to both chickens and mice. Genomic analysis results suggested that a 12-nucleotide-insertion was present at the hemagglutinin cleavage site, and both the hemagglutinin and neuraminidase genes belonged to the Yangtze River Delta lineage. RNA sequencing results revealed 566 differentially expressed genes in the H7N9-infected lungs. Moreover, transcriptome analysis revealed that over-activated antiviral signals and intense interferon-stimulated gene products possibly contributed to the high virulence of the virus in mice. Importantly, lung concentrations of inflammatory cytokines, including interleukin-1ß and interleukin-6, interferon-ß, and tumor necrosis factor-α, were upregulated in response to H7N9 virus infection. Overall, the present study provided a comprehensive understanding of H7N9 virus pathogenicity and correlated host immune responses.
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African swine fever virus (ASFV) is a large and complex DNA virus that causes a highly contagious and often lethal swine viral disease, for which no vaccine and effective treatments are available yet. Hence, ASFV presents significant economic consequences for the swine industry. A rapid and simple diagnostic method is urgently needed to monitor ASFV-specific antibodies for controlling the spread of ASFV. In this study, we chose the truncated p54 protein as an antigen and combined it with Eu-doped fluorescent microspheres as tracers to detect anti-ASFV antibodies specifically. Results showed that the truncated p54 protein had high specificity to ASFV antibody and had no cross-reactions with other swine virus antibodies. The results between our fluorescent immunochromatography test strip (FICTS) and commercial ELISA kits showed high consistency. The proposed FICTS offers a rapid, sensitive, specific, and visual method for ASFV antibody detection and shows great potential for ASF epidemic surveillance and control.
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Vírus da Febre Suína Africana , Febre Suína Africana , Febre Suína Africana/diagnóstico , Animais , Anticorpos Antivirais , Cromatografia de Afinidade , Ensaio de Imunoadsorção Enzimática , SuínosRESUMO
COVID-19 is a new respiratory illness caused by SARS-CoV-2, and has constituted a global public health emergency. Cat is susceptible to SARS-CoV-2. However, the prevalence of SARS-CoV-2 in cats remains largely unknown. Here, we investigated the infection of SARS-CoV-2 in cats during COVID-19 outbreak in Wuhan by serological detection methods. A cohort of serum samples were collected from cats in Wuhan, including 102 sampled after COVID-19 outbreak, and 39 prior to the outbreak. Fifteen sera collected after the outbreak were positive for the receptor binding domain (RBD) of SARS-CoV-2 by indirect enzyme linked immunosorbent assay (ELISA). Among them, 11 had SARS-CoV-2 neutralizing antibodies with a titer ranging from 1/20 to 1/1080. No serological cross-reactivity was detected between SARS-CoV-2 and type I or II feline infectious peritonitis virus (FIPV). In addition, we continuously monitored serum antibody dynamics of two positive cats every 10 days over 130 days. Their serum antibodies reached the peak at 10 days after first sampling, and declined to the limit of detection within 110 days. Our data demonstrated that SARS-CoV-2 has infected cats in Wuhan during the outbreak and described serum antibody dynamics in cats, providing an important reference for clinical treatment and prevention of COVID-19.
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Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/veterinária , Pandemias/veterinária , Pneumonia Viral/veterinária , Animais , COVID-19 , Gatos , China , Infecções por Coronavirus/epidemiologia , Proteínas do Nucleocapsídeo de Coronavírus , Coronavirus Felino/imunologia , Reações Cruzadas/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Imunoglobulina G/sangue , Proteínas do Nucleocapsídeo/imunologia , Fosfoproteínas , Pneumonia Viral/epidemiologia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/imunologiaRESUMO
BACKGROUND: Influenza is a severe respiratory illness that continually threatens global health. It has been widely known that gut microbiota modulates the host response to protect against influenza infection, but mechanistic details remain largely unknown. Here, we took advantage of the phenomenon of lethal dose 50 (LD50) and metagenomic sequencing analysis to identify specific anti-influenza gut microbes and analyze the underlying mechanism. RESULTS: Transferring fecal microbes from mice that survive virulent influenza H7N9 infection into antibiotic-treated mice confers resistance to infection. Some gut microbes exhibit differential features to lethal influenza infection depending on the infection outcome. Bifidobacterium pseudolongum and Bifidobacterium animalis levels are significantly elevated in surviving mice when compared to dead or mock-infected mice. Oral administration of B. animalis alone or the combination of both significantly reduces the severity of H7N9 infection in both antibiotic-treated and germ-free mice. Functional metagenomic analysis suggests that B. animalis mediates the anti-influenza effect via several specific metabolic molecules. In vivo tests confirm valine and coenzyme A produce an anti-influenza effect. CONCLUSIONS: These findings show that the severity of influenza infection is closely related to the heterogeneous responses of the gut microbiota. We demonstrate the anti-influenza effect of B. animalis, and also find that the gut population of endogenous B. animalis can expand to enhance host influenza resistance when lethal influenza infection occurs, representing a novel interaction between host and gut microbiota. Further, our data suggest the potential utility of Bifidobacterium in the prevention and as a prognostic predictor of influenza.
Assuntos
Bifidobacterium animalis , Microbioma Gastrointestinal , Infecções por Orthomyxoviridae/prevenção & controle , Animais , Bifidobacterium/isolamento & purificação , Bifidobacterium animalis/isolamento & purificação , Bifidobacterium animalis/fisiologia , Coenzima A/uso terapêutico , Fezes/microbiologia , Subtipo H7N9 do Vírus da Influenza A , Dose Letal Mediana , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/microbiologia , Infecções por Orthomyxoviridae/patologia , Valina/uso terapêuticoRESUMO
BACKGROUND: Recent studies have found that clinical pain is related to cognitive impairment. However, there remains a scarcity of systematic reviews on the influence of acute pain on attention. Laboratory-induced pain is often used to simulate acute pain. The current systematic meta-analysis aimed to evaluate the effect of induced-pain on three components of attention (orienting, alerting, and executive attention) in healthy subjects. METHODS: A systematic search of three databases was performed. Only data from studies that administered laboratory-induced pain and that also included a control group were selected. The effects of experimental pain on orienting attention, alerting attention, and executive attention were analyzed. Two reviewers assessed the studies and extracted relevant data according to the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analysis Guidelines. RESULTS: Eight studies were included in the meta-analysis. Orienting attention was marginally interrupted by pain under the invalid cue and marginally facilitated by pain under the valid cue condition. Performance on alerting attention was decreased by pain. Executive attention was not significantly affected by pain. CONCLUSION: There was moderate evidence that experimentally induced pain can produce effects on orienting and alerting attention but not on executive attention. This meta-analysis suggests that experimentally induced pain influences some aspects of attention.