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Practitioners with years of mindfulness training (MT) have a reduced attentional blink (AB), relative to novices and non-practitioners. There is still a lack of evidence regarding the impact of relatively short-term intensive traditional MT on AB. Moreover, it is unknown which component(s) of mindfulness underlie mindfulness-associated reductions in AB. Eighty-nine Chinese subjects were randomized into a MT group (N = 44) and a control (CON) group (N = 45). The participants in the CON group were waitlisted for the opportunity to participate in the training program during the 8 weeks that the MT group underwent training. Before (pretest) and after (posttest) the MT program, the subjects completed the Five-Facet Mindfulness Questionnaire (FFMQ), Peace-of-mind questionnaire (POM), and an AB task. Ultimately, 73 participants (MT group/CON group: 35/38) completed the study. From the pretest to the posttest, the MT group exhibited increases in FFMQ scores (total scores, observing subscores, and non-reactivity subscores) and POM scores, as well as improved accuracy in the AB task and a reduction in the lag-1 sparing effect. Increases in T2 accuracy in the AB correlated with improved non-reactivity. These findings broaden our understanding of the association between mindfulness and AB, and support the supposition that the skill of mindful non-reactivity plays an important role in reducing AB.

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, N = 92) and a Stroop task (Experiment 2, N = 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.

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., GRAPHICAL ABSTRACT

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-β) 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-β 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-β) 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.

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.

MicroRNAs (miRNAs) are small noncoding RNAs of 18–25 nucleotides (nt) in length that represent key regulators of many normal cellular functions through the inhibition of mRNA translation and mRNA degradation. To date, over 2 500 mature miRNAs have been identified in plants, animals and several types of viruses. Influenza A virus (IAV), which is a negative-sense, single-stranded RNA virus, does not encode viral miRNA. However, IAV infection can alter the expression of host miRNAs, either in cell culture or in host. In turn, host miRNAs regulate IAV life cycle through directly binding to IAV genome or indirectly targeting host factors associated with viral replication. In this review, we briefly summarized the role and significance of miRNA in relation to IAV pathogenesis. Understanding the role of cellular miRNAs during viral infection may be beneficial to the identification of novel therapeutic strategies to block IAV replication.

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.

Summary 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 analyze 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 titers 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.

Aged BALB/c mice 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., 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 mutation, which is located at the receptor-binding domain (RBD) of the spike (S) protein. We further found that the isolates cannot 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. IMPORTANCE Aged BALB/c mice 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.

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: We generated a mouse-adapted strain SARS-CoV-2 by serial passages in the lung of BALB/c mice. 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 demonstrated that two mutations in RBD significantly increased its binding affinity towards mouse ACE2. Significantly, TLR7/8 agonist Resiquimod block SARS-CoV-2 in vitro and in vivo. Findings: We adapted a wild-type SARS-CoV-2 by serial passages in the lung of BALB/c mice. 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 TLR7/8 agonist Resiquimod was able to protect mice against WBP-1 challenge, demonstrating 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, especially in determining the immunopathological consequences of any intervention. This study also verified the antiviral activity of TLR7/8 agonist Resiquimod against SARS-CoV-2 in vitro and in vivo. Funding Statement: This research was funded by Emergency Science and Technology Project of Hubei Province（2020FCA046）and Independent Science and Technology Innovation Fund of Huazhong Agricultural University in 2020 (2662020PY002). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The animal experiments were approved by the Research Ethics Committee, Huazhong Agricultural University, Hubei, China (HZAUMO-2020-0007). All the animal experiments were conducted in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals from the Research Ethics Committee, Huazhong Agricultural University, Hubei, China.

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-1β and interleukin-6, interferon-β, 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.

SummaryCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, and rapidly spread worldwide. Previous studies suggested cat could be a potential susceptible animal of SARS-CoV-2. Here, we investigated the infection of SARS-CoV-2 in cats by detecting specific serum antibodies. A cohort of serum samples were collected from cats in Wuhan, including 102 sampled after COVID-19 outbreak, and 39 prior to the outbreak. 15 of 102 (14.7%) cat 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 the positive samples, 11 had SARS-CoV-2 neutralizing antibodies with a titer ranging from 1/20 to 1/1080. No serological cross-reactivity was detected between the SARS-CoV-2 and type I or II feline infectious peritonitis virus (FIPV). Our data demonstrates that SARS-CoV-2 has infected cat population in Wuhan during the outbreak.

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).