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Abstract Background The spinal inflammatory signal often spreads to distant segments, accompanied by widespread pain symptom under neuropathological conditions. Multiple cytokines are released into the cerebrospinal fluid (CSF), potentially inducing the activation of an inflammatory cascade at remote segments through CSF flow. However, the detailed alteration of CSF in neuropathic pain and its specific role in widespread pain remain obscure. Methods A chronic constriction injury of the infraorbital nerve (CCI-ION) model was constructed, and pain-related behavior was observed on the 7th, 14th, 21st, and 28th days post surgery, in both vibrissa pads and hind paws. CSF from CCI-ION rats was transplanted to naïve rats through intracisternal injection, and thermal and mechanical allodynia were measured in hind paws. The alteration of inflammatory cytokines in CCI-ION’s CSF was detected using an antibody array and bioinformatic analysis. Pharmacological intervention targeting the changed cytokine in the CSF and downstream signaling was performed to evaluate its role in widespread pain. Results CCI-ION induced local pain in vibrissa pads together with widespread pain in hind paws. CCI-ION’s CSF transplantation, compared with sham CSF, contributed to vibrissa pad pain and hind paw pain in recipient rats. Among the measured cytokines, interleukin-6 (IL-6) and leptin were increased in CCI-ION’s CSF, while interleukin-13 (IL-13) was significantly reduced. Furthermore, the concentration of CSF IL-6 was correlated with nerve injury extent, which gated the occurrence of widespread pain. Both astrocytes and microglia were increased in remote segments of the CCI-ION model, while the inhibition of astrocytes in remote segments, but not microglia, significantly alleviated widespread pain. Mechanically, astroglial signal transducer and activator of transcription 3 (STAT3) in remote segments were activated by CSF IL-6, the inhibition of which significantly mitigated widespread pain in CCI-ION. Conclusion IL-6 was induced in the CSF of the CCI-ION model, triggering widespread pain via activating astrocyte STAT3 signal in remote segments. Therapies targeting IL-6/STAT3 signaling might serve as a promising strategy for the widespread pain symptom under neuropathological conditions. Graphical abstract

The continued evolution of H3 subtype avian influenza virus (AIV)—which crosses the interspecific barrier to infect humans—and the potential risk of genetic recombination with other subtypes pose serious threats to the poultry industry and human health. Therefore, rapid and accurate detection of H3 virus is highly important for preventing its spread. In this study, a method based on real-time reverse transcription recombinase-aided isothermal amplification (RT–RAA) was successfully developed for the rapid detection of H3 AIV. Specific primers and probes were designed to target the hemagglutinin (HA) gene of H3 AIV, ensuring highly specific detection of H3 AIV without cross-reactivity with other important avian respiratory viruses. The results showed that the detection limit of the RT–RAA fluorescence reading method was 224 copies/response within the 95% confidence interval, while the detection limit of the RT–RAA visualization method was 1527 copies/response within the same confidence interval. In addition, 68 clinical samples were examined and the results were compared with those of real-time quantitative PCR (RT–qPCR). The results showed that the real-time fluorescence RT–RAA and RT–qPCR results were completely consistent, and the kappa value reached 1, indicating excellent correlation. For visual detection, the sensitivity was 91.43%, the specificity was 100%, and the kappa value was 0.91, which also indicated good correlation. In addition, the amplified products of RT–RAA can be visualized with a portable blue light instrument, which enables rapid detection of H3 AIV even in resource-constrained environments. The H3 AIV RT-RAA rapid detection method established in this study can meet the requirements of basic laboratories and provide a valuable reference for the early diagnosis of H3 AIV.

With a growing global concern over food safety and animal welfare issues, the livestock and veterinary industries are undergoing unprecedented changes. These changes have not only brought challenges within each industry, but also brought unprecedented opportunities for development. In this context, the search for natural and safe products that can effectively replace traditional veterinary drugs has become an important research direction in the fields of animal husbandry and veterinary medicine. Oregano essential oil (OEO), as a natural extract, is gradually emerging in the fields of animal husbandry and veterinary medicine with its unique antibacterial, antioxidant, and multiple other biological activities. OEO not only has a wide antibacterial spectrum, effectively fighting against a variety of pathogenic microorganisms, but also, because of its natural properties, helps us to avoid traditional veterinary drugs that may bring drug residues or cause drug resistance problems. This indicates OEO has great application potential in animal disease treatment, animal growth promotion, and animal welfare improvement. At present, the application of OEO in the fields of animal husbandry and veterinary medicine has achieved preliminary results. Studies have shown that adding OEO to animal feed can significantly improve the growth performance and health status of animals and reduce the occurrence of disease. At the same time, pharmacokinetic studies in animals show that the absorption, distribution, metabolism, and excretion processes of OEO in animals shows good bioavailability. In summary, oregano essential oil (OEO), as a substitute for natural veterinary drugs with broad application prospects, is gradually becoming a research hotspot in the field of animal husbandry and veterinary medicine. In the future, we look forward to further tapping the potential of OEO through more research and practice and making greater contributions to the sustainable development of the livestock and veterinary industries.

The goose astrovirus (GAstV), a key pathogen causing visceral gout and high mortality in geese, has spread widely in China, with frequent outbreaks in recent years. Outbreaks and transmissions of this virus have been reported across China, causing considerable economic losses to the goose industry worldwide, with losses exceeding tens of billions in China alone. However, there is still no effective prevention strategy against this virus. Therefore, continuous monitoring of the genetic diversity of dominant GAstV strains is crucial for developing targeted vaccines and appropriate therapeutics. As a crucial region for goose breeding in China, Hebei Province has previously lacked reports on the epidemiology of GAstV. Hence, investigating the epidemiology of GAstV in Hebei Province is highly important. From January 2019 to December 2021, 474 samples suspected of having a GAstV infection were collected in Hebei Province in this study. Through detailed histological observations, pathological examinations, virus isolation and identification, and genetic diversity analysis, we found that GAstV-2 has become the predominant circulating genotype. However, the presence of GAstV-1 and mixed infections cannot be ignored and should receive increased attention. The findings of this study not only deepened our understanding of GAstV in waterfowl in China but also provided scientific evidence for developing effective prevention and control measures, thereby promoting the healthy development of the goose industry in China.

Abstract Neuropathic pain is difficult to treat in clinical practice, and the underlying mechanisms are insufficiently elucidated. Previous studies have demonstrated that the neuronal Fc‐gamma‐receptor type I (FcγRI) of the dorsal root ganglion (DRG) mediates antigen‐specific pain. However, the mechanisms of neuronal FcγRI in neuropathic pain remain to be explored. Here, it is found that the activation of FcγRI‐related signals in primary neurons induces neuropathic pain in a rat model. This work first reveals that sciatic nerve injury persistently activates neuronal FcγRI‐related signaling in the DRG, and conditional knockout (CKO) of the FcγRI‐encoding gene Fcgr1 in rat DRG neurons significantly alleviates neuropathic pain after nerve injury. C‐reactive protein (CRP) is increased in the DRG after nerve injury, and CRP protein of the DRG evokes pain by activating neuronal FcγRI‐related signals. Furthermore, microinjection of naive IgG into the DRG alleviates neuropathic pain by suppressing the activation of neuronal FcγRI. These results indicate that the activation of neuronal CRP/FcγRI‐related signaling plays an important role in the development of neuropathic pain in chronic constriction injury (CCI) rats. The findings may provide novel insights into the neuroimmune responses after peripheral nerve injury and suggest potential therapeutic targets for neuropathic pain.

The crucial reservoir of antibiotic resistance genes (ARGs) within the chicken intestinal microbiome poses a serious threat to both animal and human health. In China, the overuse of antibiotics has significantly contributed to the proliferation of ARGs in the chicken intestinal microbiome, which is a serious concern. However, there has been relatively little research on the diversity of resistance genes in the chicken intestinal microbiome since the implementation of the National Pilot Work Program for Action to Reduce the Use of Veterinary Antimicrobial Drugs in China. The objective of this study was to analyze the diversity of antibiotic resistance genes carried by the chicken intestinal microbiome in both standard farms (SFs), which implement antibiotic reduction and passed national acceptance, and nonstandard farms (NSFs), which do not implement antibiotic reductions, in Hebei Province. Fresh fecal samples of broiler chickens were collected from SFs (n = 4) and NSF (n = 1) and analyzed using high-throughput qPCR technology. Our findings revealed that all five farms exhibited a wide range of highly abundant ARGs, with a total of 201 ARGs and 7 MGEs detected in all fecal samples. The dominant ARGs identified conferred resistance to aminoglycosides, macrolide-lincosamide-streptomycin B (MLSB), and tetracycline antibiotics. Cellular protection mechanisms were found to be the primary resistance mechanism for these ARGs. The analysis of the co-occurrence network demonstrated a significant positive correlation between the abundance of MGEs and ARGs. The SF samples showed a significantly lower relative abundance of certain ARGs than the NSF samples (p < 0.05). The results of this study show that the abundance of ARGs demonstrated a downward trend after the implementation of the National Pilot Work Program for Action to Reduce the Usage of Veterinary Antimicrobial Drugs in Hebei Province, China.

Hebei Province is an important area for breeding broiler chickens in China, but the antimicrobial resistance and prevalence of Escherichia coli (E. coli) are still unclear. A total of 180 cloacal samples from broiler farms in Hebei Province were collected and used for the isolation and identification of E. coli. The isolates were subjected to resistance phenotyping, resistance profiling, and genotyping, and some multiresistant strains were subjected to multilocus sequence typing (MLST). The results showed that 175 strains were isolated. Among both types of broiler farms, the ampicillin resistance rate was the highest, and the meropenem resistance rate was the lowest. Serious multiresistance was present in both types of broiler farms. Thirty strains of multidrug-resistant E. coli were typed by MLST to obtain a total of 18 ST types, with ST10 being the most prevalent. This study was to simply analyze the antimicrobial resistance and prevalence of E. coli in broiler chickens in Hebei Province after the implementation of the pilot work program of action to reduce the use of veterinary antimicrobials in standard farms (SFs) and nonstandard farms (NSFs). This study will provide a research basis and data support for the prevention and control of E. coli in Hebei.

IntroductionInfluenza A viruses (IAVs) are important pathogens of respiratory infections, causing not only seasonal influenza but also influenza pandemics and posing a global threat to public health. IAVs infection spreads rapidly, widely, and across species, causing huge losses, especially zoonotic IAVs infections that are more harmful. Fast and sensitive detection of IAVs is critical for controlling the spread of this disease.MethodsHere, a real-time reverse transcription recombinase-aided amplification (real-time RT-RAA) assay targeting conserved positions in the matrix protein gene (M gene) of IAVs, is successfully established to detect IAVs. The assay can be completed within 20 min at 42°C.ResultsThe sensitivity of the real-time RT-RAA assay was 142 copies per reaction at 95% probability, which was comparable to the sensitivity of the RT-qPCR assay. The specificity assay showed that the real-time RT-RAA assay was specific to IAVs, and there was no cross-reactivity with other important viruses. In addition, 100%concordance between the real-time RT-RAA and RT-qPCR assays was achieved after testing 120 clinical specimens.DiscussionThe results suggested that the real-time RT-RAA assay we developed was a specific, sensitive and reliable diagnostic tool for the rapid detection of IAVs.

Abstract Background Classical understanding of allergic conjunctivitis (ACJ) suggests that ocular itch results from a mast cell-dependent inflammatory process. However, treatments that target inflammatory mediators or immune cells are often unsatisfying in relieving the stubborn itch symptom. This suggests that additional mechanisms are responsible for ocular itch in ACJ. In this study, we aim to determine the role of neuronal FcεRIa in allergic ocular itch. Methods Calcium imaging was applied to observe the effect of IgE-immune complex in trigeminal neurons. Genomic FcεRIa knockout mice and adeno-associated virus (AAV) mediated sensory neuron FcεRIa knockdown mice were used in conjunction with behavioral tests to determine ocular itch. In addition, immunohistochemistry, Western blot and quantitative RT-PCR were used for in vitro experiments. Results We found that FcεRIα was expressed in a subpopulation of conjunctiva sensory neurons. IgE-IC directly activated trigeminal neurons and evoked acute ocular itch without detectible conjunctival inflammation. These effects were attenuated in both a global FcεRIa-knockout mice and after sensory neuronal-specific FcεRIa-knockdown in the mouse trigeminal ganglion. In an ovalbumin (OVA) induced murine ACJ model, FcεRIα was found upregulated in conjunctiva-innervating CGRP+ sensory neurons. Sensory neuronal-specific knockdown of FcεRIa significantly alleviated ocular itch in the ACJ mice without affecting the immune cell infiltration and mast cell activation in conjunctiva. Although FcεRIα mRNA expression was not increased by IgE in dissociated trigeminal ganglion neurons, FcεRIα protein level was enhanced by IgE in a cycloheximide-resistance manner, with concordant enhancement of neuronal responses to IgE-IC. In addition, incremental sensitization gradually enhanced the expression of FcεRIα in small-sized trigeminal neurons and aggravated OVA induced ocular itch. Conclusions Our study demonstrates that FcεRIα in pruriceptive neurons directly mediates IgE-IC evoked itch and plays an important role in ocular itch in a mouse model of ACJ. These findings reveal another axis of neuroimmune interaction in allergic itch condition independent to the classical IgE-mast cell pathway, and might suggest novel therapeutic strategies for the treatment of pruritus in ACJ and other immune-related disorders.

Ghost imaging is a novel imaging technique that utilizes the intensity correlation property of an optical field to retrieve information of the scene being measured. Due to the advantages of simple structure, high detection efficiency, etc., ghost imaging exhibits broad application prospects in the fields of space remote sensing, optical encryption transmission, medical imaging, and so on. At present, ghost imaging is gradually developing toward practicality, in which ghost imaging of moving targets is becoming a much-needed breakthrough link. At this stage, we can improve the imaging speed and improve the imaging quality to seek a more optimized ghost imaging scheme for moving targets. Based on the principle of moving target ghost imaging, this review summarizes and compares the existing methods for ghost imaging of moving targets. It also discusses the research direction and the technical challenges at the current stage to provide references for further promotion of the instantiation of ghost imaging applications.

Currently, it is believed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an airborne virus, and virus-containing aerosol particles have been found concurrent with the onset of COVID-19, which may contribute to the noncontact transmission of SARS-CoV-2. Exploring agents to block SARS-CoV-2 transmission is of great importance to prevent the COVID-19 pandemic. In this study, we found that inactivated Parapoxvirus ovis (iORFV), a kind of immunomodulator, could compress the proportion of small particle aerosols exhaled by Syrian golden hamsters. Notably, the concentration of SARS-CoV-2 RNA-containing aerosol particles was significantly reduced by iORFV in the early stages after viral inoculation. Importantly, smaller aerosol particles (

Since it was first identified in 1956, the H11 subvariant influenza virus has been reported worldwide. However, due to the low pathogenicity of the H11 subvariant and the absence of its widespread transmission among humans, there are only a few reports on the etiology of the H11 subvariant influenza virus. Therefore, in the present study, we isolated a strain of the H11N3 avian influenza virus (AIV) from poultry feces from the live poultry market in the southeast coastal region of China. Considering that the H11 subvariant is known to cause infections in humans and to enrich the knowledge of the H11 subvariant of the avian influenza virus, the genetics, pathogenicity, and transmissibility of the isolate were studied. The phylogenetic analysis indicated that the H11N3 isolate was of Eurasian origin and carried genes closely related to duck H7N2 and H4N6. The receptor binding analysis revealed that the H11N3 isolate only acquired a binding affinity for avian-derived receptors. In the respiratory system of mice, the isolate could directly cause infection without adaptation. In addition, the results from transmission experiments and antibody detection in guinea pigs demonstrated that H11N3 influenza viruses can efficiently transmit through the respiratory tract in mammalian models. Direct infection of the H11N3 influenza virus without adaptation in the mouse models and aerosol transmission between guinea pig models confirms its pandemic potential in mammals, underscoring the importance of monitoring rare influenza virus subtypes in future studies.

Summary: To date, intermediate hosts of SARS-CoV-2 remain obscure and controversial. Several studies have shown that SARS-CoV-2-related pangolin coronavirus (Pangolin-CoV) has a high sequence similarity to SARS-CoV-2 and might be the initial source of SARS-CoV-2; however, the biological characteristics of Pangolin-CoV are still largely unknown. In this study, we evaluated the pathogenicity and transmissibility of Pangolin-CoV in Syrian golden hamsters Mesocricetus auratus (Linnaeus, 1758) and compared it with SARS-CoV-2. Pangolin-CoV could effectively infect hamsters, showed similar tissue tropism to SARS-CoV-2 and replicated efficiently in the respiratory system and brain. The infected hamsters had no weight loss but had obvious viral shedding and lung pathological injury. Notably, Pangolin-CoV could transmit between hamsters by direct contact but not via aerosols, and the infected hamsters could exhale infectious viral aerosols (>1 μm). These results highlight the importance of continuous monitoring of coronaviruses in pangolins owing to the potential threat of Pangolin-CoV to human health.

Pseudorabies (PR) is a serious disease affecting the pig industry in China, and it is very important to understand the epidemiology of pseudorabies virus (PRV). In the present study, 693 clinical samples were collected from Bartha-K61 vaccinated pigs with symptoms of suspected PRV infection between January 2017 and December 2018. All cases were referred for full clinical autopsy with detailed examination of histopathological examination, virus isolation and genetic evolution analysis of the PRV glycoprotein E (gE) gene. In addition, PRV gE antibodies in 3,449 serum samples were detected by the enzyme-linked immunosorbent assay (ELISA). The clinical data revealed that abortion and stillbirth are the most frequent appearances in pregnant sows of those cases. Histopathological examination exhibited a variety of pathological lesions, such as lobar pneumonia, hepatitis, lymphadenitis, nephritis, and typical nonsuppurative encephalitis. A total of 248 cases tested positive for the PRV gE gene. 11 PRV variants were isolated and confirmed by gE gene sequencing and phylogenetic analysis. These strains had 97.1%-100.0% nucleotide homology with the PRV reference strains. Notably, the isolated strains were highly homologous and clustered in the same branch as HSD-1/2019, which caused human acute encephalitis. Serological tests showed that the positive rate of PRV gE antibody in the 3449 serum samples collected from the Hebei Province was 46.27%. In conclusion, PRV variant strains Are high prevalence in the Hebei Province, which not only causes huge economic losses to the breeding industry but also potentially poses a threat to public health.

Influenza virus is a serious threat to global human health and public health security. There is an urgent need to develop new anti-influenza drugs. Lentinan (LNT) has attracted increasing attention in recent years. As potential protective agent, LNT has been shown to have anti-tumor, anti-inflammatory, and antiviral properties. However, there has been no further research into the anti-influenza action of lentinan in vivo, and the mechanism is still not fully understood. In this study, the anti-influenza effect and mechanism of Lentinan were studied in the Institute of Cancer Research (ICR) mouse model. The results showed that Lentinan had a high degree of protection in mice against infection with influenza A virus, delayed the emergence of clinical manifestations, improved the survival rate of mice, significantly prolonged the middle survival days, attenuated the weight loss, and reduced the lung coefficient of mice. It alleviated the pathological damage of mice infected with the influenza virus and improved blood indices. Lentinan treatment considerably inhibited inflammatory cytokine (TNF-α, IL-1β, IL-4, IL-5, IL-6) levels in the serum and lung and improved IFN-γ cytokine levels, which reduced cytokine storms caused by influenza virus infection. The underlying mechanisms of action involved Lentinan inhibiting the inflammatory response by regulating the TLR4/MyD88 signaling pathway. This study provides a foundation for the clinical application of Lentinan, and provides new insight into the development of novel immunomodulators.

Previous studies have shown that B.1.351 and other variants have extended the host range of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to mice. Sustained transmission is a prerequisite for viral maintenance in a population. However, no evidence of natural transmission of SARS-CoV-2 in wild mice has been documented to date. Here, we evaluated the replication and contact transmission of the B.1.351 variant in mice and rats. The B.1.351 variant could infect and replicate efficiently in the airways of mice and rats. Furthermore, the B.1.351 variant could not be transmitted in BALB/c or C57BL/6 mice but could be transmitted with moderate efficiency in rats by direct contact. Additionally, the B.1.351 variant did not transmit from inoculated Syrian hamsters to BALB/c mice. Moreover, the mouse-adapted SARS-CoV-2 strain C57MA14 did not transmit in mice. In summary, the risk of B.1.351 variant transmission in mice is extremely low, but the transmission risk in rats should not be neglected. We should pay more attention to the potential natural transmission of SARS-CoV-2 variants in rats and their possible spillback to humans.

The pandemic of respiratory diseases, such as coronavirus disease 2019 (COVID-19) and influenza, has imposed significant public health and economic burdens on the world. Wearing masks is an effective way to cut off the spread of the respiratory virus. However, due to cultural differences and uncomfortable wearing experiences, not everyone is willing to wear masks; there is an urgent need to find alternatives to masks. In this study, we tested the disinfection effect of a portable ionizer on pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (strain V34) and influenza A virus (strain CA04). Negative ions significantly reduced the concentration of particulate matter in the air above and effectively disinfected viruses stuck to the solid plate at the level of both nucleic acid and virus titer. The disinfection efficiency was >99.8% after 1-h exposure. Moreover, negative ions effectively disinfected aerosolized viruses; the disinfection efficiency was more than 87.77% after purification for 10 min. Furthermore, negative ions had a significant protective effect on susceptible animals exposed to viral aerosols. When the negative ionizer was switched from off to on, the inhalation 50% infective dose (ID50) for golden hamsters challenged with SARS-CoV-2 rose from 9.878 median tissue culture infective dose (TCID50) [95% confidence interval (CI), 6.727–14.013 TCID50] to 43.891 TCID50 (95% CI, 29.31–76.983 TCID50), and the inhalation ID50 for guinea pigs challenged with influenza A virus rose from 6.696 TCID50 (95% CI, 3.251–9.601 TCID50) to 28.284 TCID50 (95% CI, 19.705–40.599 TCID50). In the experiment of transmission between susceptible animals, negative ions 100% inhibited the aerosol transmission of SARS-CoV-2 and influenza A virus. Finally, we tested the safety of negative ion exposure. Balb/c mice exposed to negative ions for 4 weeks showed no abnormalities in body weight, blood routine analysis, and lung pathology. Our study demonstrates that air ions can be used as a safe and effective means of blocking respiratory virus transmission and contribute to pandemic prevention and control.

Since December 2019, coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a great challenge to the world's public health system. Nosocomial infections have occurred frequently in medical institutions worldwide during this pandemic. Thus, there is an urgent need to construct an effective surveillance and early warning system for pathogen exposure and infection to prevent nosocomial infections in negative-pressure wards. In this study, visualization and construction of an infection risk assessment of SARS-CoV-2 through aerosol and surface transmission in a negative-pressure ward were performed to describe the distribution regularity and infection risk of SARS-CoV-2, the critical factors of infection, the air changes per hour (ACHs) and the viral variation that affect infection risk. The SARS-CoV-2 distribution data from this model were verified by field test data from the Wuhan Huoshenshan Hospital ICU ward. ACHs have a great impact on the infection risk from airborne exposure, while they have little effect on the infection risk from surface exposure. The variant strains demonstrated significantly increased viral loads and risks of infection. The level of protection for nurses and surgeons should be increased when treating patients infected with variant strains, and new disinfection methods, electrostatic adsorption and other air purification methods should be used in all human environments. The results of this study may provide a theoretical reference and technical support for reducing the occurrence of nosocomial infections.

Abstract Background As a classic innate immunity pathway, Toll-like receptor 4 (TLR4) signaling has been intensively investigated for its function of pathogen recognition. The receptor is located not only on immune cells but also on sensory neurons and spinal glia. Recent studies revealed the involvement of neuronal TLR4 in different types of pain. However, the specific role of TLR4 signaling in the pain symptom of endometriosis (EM) remains obscure. Methods The rat endometriosis model was established by transplanting uterine horn tissue into gastrocnemius. Western blotting and/or immunofluorescent staining were applied to detect high mobility group box 1 (HMGB1), TLR4, myeloid differentiation factor-88 adaptor protein (MyD88), and nuclear factor kappa-B-p65 (NF-κB-p65) expression, as well as the activation of astrocyte and microglia. The antagonist of TLR4 (LPS-RS-Ultra, LRU) and MyD88 homodimerization inhibitory peptide (MIP) were intrathecally administrated to assess the behavioral effects of blocking TLR4 signaling on endometriosis-related pain. Results Mechanical hyperalgesia was observed at the graft site, while HMGB1 was upregulated in the implanted uterine tissue, dorsal root ganglion (DRG), and spinal dorsal horn (SDH). Compared with sham group, upregulated TLR4, MyD88, and phosphorylated NF-κB-p65 were detected in the DRG and SDH in EM rats. The activation of astrocytes and microglia in the SDH was also confirmed in EM rats. Intrathecal application of LRU and MIP alleviated mechanical pain on the graft site of EM rats, with decreased phosphorylation of NF-κB-p65 in the DRG and reduced activation of glia in the SDH. Conclusions HMGB1-TLR4-MyD88 signaling pathway in the DRG and SDH may involve in endometriosis-related hyperpathia. Blockade of TLR4 and MyD88 might serve as a potential treatment for pain in endometriosis.

Constraining the rise in atmospheric oxygen through the early Earth is important to understand the evolution of complex life. Here, the authors find that a major rise in atmospheric oxygen level occurred after the Great Oxidation Event, followed by pO2 within 1% of present atmospheric level through most of the Proterozoic Eon (2.4 to 0.65 Ga).

Orf is an important zoonotic disease caused by the Orf virus (ORFV) which can cause contagious pustular dermatitis in goats and sheep. Orf is widespread in most sheep-raising countries in the world, causing huge economic losses. Although diagnostic methods for ORFV infection already exist, it is still necessary to develop a time-saving, labor-saving, specific, low-cost and visual diagnostic method for rapid detection of ORFV in the field and application in grassroots laboratories. This study establishes a DNA extraction–free, real-time, visual recombinase–aided amplification (RAA) method for the rapid detection of ORFV. This method is specific to ORFV and does not cross-react with other common DNA viruses. The detection limits of the real-time RAA and visual judgment of the RAA assay at 95% probability were 13 and 21 copies per reaction for ORFV, respectively. Compared with qPCR, the sensitivity and specificity of the real-time RAA assay were 100%, and those of the visual RAA assay were 92.31% and 100.0%, respectively. The DNA extraction–free visual detection method of RAA established in this study can meet the needs of rapid onsite detection and grassroots laboratories and has important reference value and significance for the early diagnosis of diseased animals.

The frequent emergence of SARS-CoV-2 variants thwarts the prophylactic and therapeutic countermeasures confronting COVID-19. Among them, the Delta variant attracts widespread attention due to its high pathogenicity and fatality rate compared with other variants. However, with the emergence of new variants, studies on Delta variants have been gradually weakened and ignored. In this study, a replication-competent recombinant virus carrying the S protein of the SARS-CoV-2 Delta variant was established based on the vesicular stomatitis virus (VSV), which presented a safe alternative model for studying the Delta variant. The recombinant virus showed a replication advantage in Vero E6 cells, and the viral titers reach 107.3 TCID50/mL at 36 h post-inoculation. In the VSV-vectored recombinant platform, the spike proteins of the Delta variant mediated higher fusion activity and syncytium formation than the wild-type strain. Notably, the recombinant virus was avirulent in BALB/c mice, Syrian hamsters, 3-day ICR suckling mice, and IFNAR/GR−/− mice. It induced protective neutralizing antibodies in rodents, and protected the Syrian hamsters against the SARS-CoV-2 Delta variant infection. Meanwhile, the eGFP reporter of recombinant virus enabled the visual assay of neutralizing antibodies. Therefore, the recombinant virus could be a safe and convenient surrogate tool for authentic SARS-CoV-2. This efficient and reliable model has significant potential for research on viral-host interactions, epidemiological investigation of serum-neutralizing antibodies, and vaccine development.

Background: There is a growing need to offer appropriate services to persons with mild cognitive impairment (MCI) and dementia who are faced with depression and anxiety distresses beyond traditional pharmacological treatment. Dance-based interventions as multi-dimensional interventions address persons' physical, emotional, social, and spiritual aspects of well-being. However, no meta-analysis of randomized controlled treatment trials (RCTs) has examined the effectiveness of dance-based interventions on depression and anxiety among persons with MCI and dementia, and the results of RCTs are inconsistent. The study aimed to examine the effectiveness of dance-based interventions on depression (a primary outcome) and anxiety (a secondary outcome) among persons with MCI and dementia.Methods: A systematic review with meta-analysis was conducted. The inclusion criteria were: population: people of all ages with MCI and dementia; intervention: dance-based interventions; control group: no treatment, usual care, or waiting list group; outcome: depression and anxiety; study design: published or unpublished RCTs. Seven electronic databases (Cochrane, PsycINFO, Web of Science, PubMed, EBSCO, CNKI, WanFang) were searched from 1970 to March 2021. Grey literature and reference lists from relevant articles were also searched and reviewed. The Cochrane “Risk of Bias” tool was used to assess study quality. RevMan 5.4 was used for meta-analysis and heterogeneity was investigated by subgroup and sensitivity analysis. GRADE was applied to assess the evidence quality of depression and anxiety outcomes.Results: Five randomized controlled trials were identified. Sample sizes ranged from 21 to 204. The risk of bias was low, except for being rated as high or unclear for most included studies in two domains: allocation concealment, blinding participants and personnel. Meta-analysis of depression outcome showed no heterogeneity (I2 = 0%), indicating that the variation in study outcomes did not influence the interpretation of results. There were significant differences in decreasing depression in favor of dance-based interventions compared with controls [SMD = −0.42, 95% CI (−0.60, −0.23), p < 0.0001] with a small effect size (Cohen's d = 0.3669); Compared with the post-intervention data, the follow-up data indicated diminishing effects (Cohen's d = 0.1355). Dance-based interventions were more effective in reducing depression for persons with dementia than with those having MCI, and were more effective with the delivery frequency of 1 h twice a week than 35 min 2–3 times a week. Also, one included RCT study showed no significant benefit on anxiety rating scores, which demonstrated small effect sizes at 6 weeks and 12 weeks (Cohen's d = 0.1378, 0.1675, respectively). GRADE analysis indicated the evidence quality of depression was moderate, and the evidence quality of anxiety was low.Conclusions: Dance-based interventions are beneficial to alleviate depression among persons with MCI and dementia. More trials of high quality, large sample sizes are needed to gain more profound insight into dance-based interventions, such as their effects of alleviating anxiety, and the best approaches to perform dance-based interventions.

Abstract Background Influenza A virus (IAV) continues to pose serious threats to public health. The current prophylaxis and therapeutic interventions for IAV requires frequent changes due to the continuous antigenic drift and antigenic shift of IAV. Emerging evidence indicates that the host microRNAs (miRNAs) play critical roles in intricate host-pathogen interaction networks. Cellular miRNAs may directly target virus to inhibit its infection and be developed as potential anti-virus drugs. Methods In this study, we established a broad-spectrum anti-IAV miRNA screening method using miRanda software. The screened miRNAs were further verified by luciferase assay, viral protein expression assay and virus replication assay. Results Five cellular miRNAs (miR-188-3p, miR-345-5p, miR-3183, miR-15-3p and miR-769-3p), targeting 99.96, 95.31, 92.9, 94.58 and 97.24% of human IAV strains recorded in NCBI, respectively, were chosen for further experimental verification. Finally, we found that miR-188-3p downregulated PB2 expression at both mRNA and protein levels by directly targeted the predicted sites on PB2 and effectively inhibited the replication of IAV (H1N1, H5N6 and H7N9) in A549 cells. Conclusions This is the first report screening cellular miRNAs that broad-spectrum inhibiting IAV infection. These findings suggested that cellular miR-188-3p could be used for RNAi-mediated anti-IAV therapeutic strategies.

Inspired by human vision, retina-like imaging has the feature of rotation and scaling invariance, which is beneficial for target tracking and recognition. However, there is a limitation that the center of field of view (FOV) should match with the target centroid. Currently, there is no effective method to quantitatively estimate the effects from this mismatch. To solve the issue, a novel evaluation method is proposed by applying the log-polar transform and Fourier transform. Then reconstruct the target image by exchanging magnitude and phase information between the target image and its rotated or scaled counterpart. Using two current methods of digital image processing, scale-invariant feature transform (SIFT) and biaxial projection similarity analysis (BPS), as evaluation criteria, the proposed method performs efficiently for all eccentric angles. Simulation results show that for a specific target, the invariance of rotation and scaling works effectively for a value above 0.69.

Abstract Ice accretion on wind turbine blades is one of the major faults affecting the operational safety and power generation efficiency of wind turbines. Current icing detection methods are based on either meteorological observing system or extra condition monitoring system. Compared with current methods, icing detection using the intrinsic supervisory control and data acquisition (SCADA) data of wind turbines has plenty of potential advantages, such as low cost, high stability, and early icing detection ability. However, there have not been deep investigations in this field at present. In this paper, a novel intelligent wind turbine blade icing detection method based on the wind turbine SCADA data is proposed. This method consists of three processes: SCADA data preprocessing, automatic feature extraction, and ensemble icing detection model construction. Specifically, deep autoencoders network is employed to learn multilevel fault features from the complex SCADA data adaptively. And the ensemble technique is utilized to make full use of all the extracted features from different hidden layers of the deep autoencoders network to build the ensemble icing detection model. The effectiveness of the proposed method is validated using the data collected from actual wind farms. The experimental results reveal that the proposed method is able to not only adaptively extract valuable fault features from the complex SCADA data, but also obtains higher detection accuracy and generalization capability compared with conventional machine learning models and individual deep learning model.

COVID-19 was officially declared a global pandemic disease on 11 March 2020, with severe implications for healthcare systems, economic activity, and human life worldwide. Fast and sensitive amplification of the severe acute respiratory syndrome virus 2 (SARS-CoV-2) nucleic acids is critical for controlling the spread of this disease. Here, a real-time reverse transcription recombinase-aided amplification (RT-RAA) assay, targeting conserved positions in the nucleocapsid protein gene (N gene) of SARS-CoV-2, was successfully established for SARS-CoV-2. The assay was specific to SARS-CoV-2, and there was no cross-reaction with other important viruses. The sensitivity of the real-time RT-RAA assay was 142 copies per reaction at 95% probability. Furthermore, 100% concordance between the real-time RT-RAA and RT-qPCR assays was achieved after testing 72 clinical specimens. Further linear regression analysis indicated a significant correlation between the real-time RT-RAA and RT-qPCR assays with an R2 value of 0.8149 (p < 0.0001). In addition, the amplicons of the real-time RT-RAA assay could be directly visualized by a portable blue light instrument, making it suitable for the rapid amplification of SARS-CoV-2 in resource-limited settings. Therefore, the real-time RT-RAA method allows the specific, sensitive, simple, rapid, and reliable detection of SARS-CoV-2.

Avian influenza viruses (AIVs) have the potential for cross-species transmission and pandemics. In recent years, clade 2.3.4.4 H5N6 AIVs are prevalent in domestic poultry, posing a threat to the domestic poultry industry and public health. In this study, two strains of H5N6 AIVs were isolated from chickens in Hebei, China, in 2019: A/chicken/Hebei/HB1907/2019(H5N6) and A/chicken/Hebei/HB1905/2019(H5N6). Phylogenetic analysis showed that both viral HA genes clustered in the 2.3.4.4h clade. Receptor binding analysis showed that the HB1905 strain preferentially binds to α-2,3-linked sialic acid (SA) receptors, while the HB1907 strain preferentially binds to α-2,3- and α-2,6-linked sialic acid (SA) receptors. During early infection, the HB1907 strain is highly replicable in MDCK cells, more so than the HB1905 strain. Pathogenicity assays in mice showed that both viruses could replicate in the lungs without prior adaptation, with HB1907 being more highly pathogenic in mice than the HB1905 strain. Significantly, both the HB1905 and HB1907 strains can be transmitted through direct contact among guinea pigs, but the transmission efficiency of the HB1907 strain through contact between guinea pigs is much greater than that of the HB1905 strain. These results strengthen the need for ongoing surveillance and early warning of H5N6 AIVs in poultry.

Throughout the last decade, H5N6 avian influenza viruses (AIVs) circulating in poultry and infecting humans have caused increasing global concerns that they might become a pandemic threat to global health. Since AIVs could occasionally cause asymptomatic infections in geese, virus monitoring in such a host should be critical to the control of cross-species infection. In addition, previous studies showed that clade 2.3.4.4h H5N6 AIVs could infect mammals without adaptation. However, the pathogenicity and transmissibility of goose-origin clade 2.3.4.4h H5N6 AIVs in mammals remain unknown. In this study, two H5N6 AIVs were isolated from a domestic chicken (A/chicken/Hebei CK05/2019 (H5N6)) and a goose (A/goose/Hebei/GD07/2019(H5N6)). This study is the first to evaluate the pathogenicity and transmissibility of goose-origin clade 2.3.4.4h H5N6 AIVs in mammals by comparison with chicken-origin 2.3.4.4h H5N6 AIVs. The CK05 virus had an affinity for α-2,3-receptors, while the GD07 virus had an affinity for both α-2,3-and α-2,6-receptors. The GD07 virus had a higher replication capacity in vitro and more severe pathogenicity in mice than the CK05 virus. The CK05 virus could not be transmitted effectively among guinea pigs, whereas the GD07 virus could be transmitted through direct contact among guinea pigs. The results of this study indicated the potential health threat of clade 2.3.4.4h H5N6 AIVs to mammals and emphasized the importance of continuous monitoring of H5N6 AIVs, especially in waterfowl.

Prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides protective immunity against reinfection. However, whether prior infection blocks SARS-CoV-2 transmission is not yet clear. Here, we evaluated the impact of prior infection on SARS-CoV-2 transmission in Syrian hamsters. Our results showed that prior infection significantly reduced SARS-CoV-2 replication in Syrian hamsters, but sterilizing immunity was not achieved. Prior infection blocked the airborne transmission of SARS-CoV-2 from previously infected Syrian hamsters to naïve Syrian hamsters and previously infected Syrian hamsters. Moreover, prior infection substantially reduced the efficiency of direct contact transmission between previously infected Syrian hamsters. However, prior infection had limited impact on SARS-CoV-2 transmission from previously infected Syrian hamsters to naïve Syrian hamsters via direct contact in the early course of infection. Human reinfection and SARS-CoV-2 transmission between a previously infected population and a healthy population would be likely, and a higher vaccination coverage rate was needed to reach herd immunity. Our work will aid the implementation of appropriate public health and social measures to control coronavirus infectious disease 2019 (COVID-19) pandemic.

Environmental transmission of viruses to humans has become an early warning for potential epidemic outbreaks, such as SARS-CoV-2 and influenza virus outbreaks. Recently, an H7N9 virus, A/environment/Hebei/621/2019 (H7N9), was isolated by environmental swabs from a live poultry market in Hebei, China. We found that this isolate could be transmitted by direct contact and aerosol in mammals. More importantly, after 5 passages in mice, the virus acquired two adaptive mutations, PB1-H115Q and B2-E627K, exhibiting increased virulence and aerosol transmissibility. These results suggest that this H7N9 virus might potentially be transmitted between humans through environmental or airborne routes.

The whole world is suffering from the coronavirus disease 2019 (COVID-19) pandemic, induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through angiotensin-converting enzyme 2 (ACE2). Neurological manifestations in COVID-19 patients suggested the invasion of SARS-CoV-2 into the central nervous system. The present study mapped the expression level of ACE2 in 12 brain regions through immunohistochemistry and detected ACE2 in endothelial cells and non-vascular cells. The comparison among brain regions found that pons, visual cortex, and amygdala presented a relatively high level of ACE2. In addition, this study demonstrates that the protein level of ACE2 was downregulated in the basal nucleus, hippocampus and entorhinal cortex, middle frontal gyrus, visual cortex, and amygdala of the brain with Alzheimer’s disease (AD) pathology. Collectively, our results suggested that ACE2 was expressed discriminatorily at different human brain regions, which was downregulated in the brain with AD pathology. This may contribute to a comprehensive understanding of the neurological symptoms caused by SARS-CoV-2 and provide clues for further research on the relationship between COVID-19 and AD.

Neuropeptide Y (NPY) signaling plays an essential role in gating the pruritic afferent information in the spinal cord. Recent studies revealed that the aging process down-regulated the expression of NPY in the central nervous system. We propose that the lack of spinal NPY may be involved in certain types of pruritus in the elderly population. This study was designed to investigate the role of NPY in aging-induced itch using the senile mouse model. The expression of NPY in the spinal dorsal horn was compared between young (2 months old) and aged (24 months old) mice. Western blotting and immunohistochemistry showed that the expression of NPY was significantly reduced in the spinal dorsal horn in aged mice. In addition, a neuronal maker of apoptosis, TUNEL, was detected in the NPY positive neurons only in the aged spinal cord. Behavioral assay indicated that light mechanical stimulus evoked significantly more scratching in the aged than in the young mice, whereas chemical-evoked itch and pain-related behaviors were not altered. Intrathecal injection of either NPY or LP-NPY, a NPY receptor 1 (NPY1R) agonist, significantly alleviated the mechanically evoked itch in aged mice without altering the responses to chemical pruritogens. Our study suggested that downregulation of spinal NPY in the aged mice might play a role in the higher incidence of the mechanically evoked itch than that in the young mice. Therapies targeting the NPY system might serve as a potential strategy for alleviating the pruritic symptoms among the elderly population.

With the development of modern pig raising technology, the increasing density of animals in pig houses leads to the accumulation of microbial aerosols in pig houses. It is an important prerequisite to grasp the characteristics of bacteria in aerosols in different pig houses to solve the problems of air pollution and disease prevention and control in different pig houses. This work investigated the effects of growth stages on bacterial aerosol concentrations and bacterial communities in pig houses. Three traditional types of closed pig houses were studied: farrowing (FAR) houses, weaning (WEA) houses, and fattening (FAT) houses. The Andersen six-stage sampler and high-volume air sampler were used to assess the concentrations and size distribution of airborne bacteria, and 16S rRNA gene sequencing was used to identify the bacterial communities. We found that the airborne bacterial concentration, community richness, and diversity index increased with pig age. We found that Acinetobacter, Erysipelothrix, Streptococcus, Moraxella, and Aerococcus in the microbial aerosols of pig houses have the potential risk of causing disease. These differences lead us to believe that disinfection strategies for pig houses should involve a situational focus on environmental aerosol composition on a case-by-case basis.

Unlike traditional optical imaging schemes, computational ghost imaging (CGI) provides a way to reconstruct images with the spatial distribution information of illumination patterns and the light intensity collected by a single-pixel detector or bucket detector. Compared with stationary scenes, the relative motion between the target and the imaging system in a dynamic scene causes the degradation of reconstructed images. Therefore, we propose a time-variant retina-like computational ghost imaging method for axially moving targets. The illuminated patterns are specially designed with retina-like structures, and the radii of foveal region can be modified according to the axial movement of target. By using the time-variant retina-like patterns and compressive sensing algorithms, high-quality imaging results are obtained. Experimental verification has shown its effectiveness in improving the reconstruction quality of axially moving targets. The proposed method retains the inherent merits of CGI and provides a useful reference for high-quality GI reconstruction of a moving target.

Objective Influenza season occurs every year in China, but its presentation was unusual in the period from December 2017 to early 2018. During this period, influenza activity was increasing across the country and was much greater than during the same period in previous years, with great harm to people’s health. Methods In this study, we isolated two human influenza virus strains—A/Hebei/F076/2018(H1N1) and B/Hebei/16275B/2018—from patients with severe influenza in Hebei, China, during the flu season in January 2018, and explored their genetic characteristics, pathogenicity, and transmissibility. Results A/Hebei/F076/2018(H1N1) belongs to the human-like H1N1 influenza virus lineage, whereas B/Hebei/16275B/2018 belongs to the Victoria lineage and is closely related to the World Health Organization reference strain B/Brisbane/60/2008. Pathogenicity tests revealed that A/Hebei/F076/2018(H1N1) replicated much more strongly in mice, with mice exhibiting 40% mortality, whereas B/Hebei/16275B/2018 was not lethal. Both viruses could be transmitted through direct contact and by the aerosol route between guinea pigs, but the H1N1 strain exhibited higher airborne transmissibility. Conclusions These results may contribute to the monitoring of influenza mutation and the prevention of an influenza outbreak.

Single-pixel imaging, with the advantages of a wide spectrum, beyond-visual-field imaging, and robustness to light scattering, has attracted increasing attention in recent years. Fourier single-pixel imaging (FSI) can reconstruct sharp images under sub-Nyquist sampling. However, the conventional FSI has difficulty balancing imaging quality and efficiency. To overcome this issue, we proposed a novel approach called complementary Fourier single-pixel imaging (CFSI) to reduce the number of measurements while retaining its robustness. The complementary nature of Fourier patterns based on a four-step phase-shift algorithm is combined with the complementary nature of a digital micromirror device. CFSI only requires two phase-shifted patterns to obtain one Fourier spectral value. Four light intensity values are obtained by loading the two patterns, and the spectral value is calculated through differential measurement, which has good robustness to noise. The proposed method is verified by simulations and experiments compared with FSI based on two-, three-, and four-step phase shift algorithms. CFSI performed better than the other methods under the condition that the best imaging quality of CFSI is not reached. The reported technique provides an alternative approach to realize real-time and high-quality imaging.

The properties of the human eye retina, including space-variant resolution and gaze characters, provide many advantages for numerous applications that simultaneously require a large field of view, high resolution, and real-time performance. Therefore, retina-like mechanisms and sensors have received considerable attention in recent years. This paper provides a review of state-of-the-art retina-like imaging techniques and applications. First, we introduce the principle and implementing methods, including software and hardware, and describe the comparisons between them. Then, we present typical applications combined with retina-like imaging, including three-dimensional acquisition and reconstruction, target tracking, deep learning, and ghost imaging. Finally, the challenges and outlook are discussed to further study for practical use. The results are beneficial for better understanding retina-like imaging.

Since 2013, H7N9 and H5N6 avian influenza viruses (AIVs) have caused sporadic human infections and deaths and continued to circulate in the poultry industry. Since 2014, H7N6 viruses which might be reassortants of H7N9 and H5N6 viruses, have been isolated in China. However, the biological properties of H7N6 viruses are unknown. Here, we characterize the receptor binding preference, pathogenicity and transmissibility of a H7N6 virus A/chicken/Hubei/00095/2017(H7N6) (abbreviated HB95), and a closely related H7N9 virus, A/chicken/Hubei/00093/2017(H7N9) (abbreviated HB93), which were isolated from poultry in Hubei Province, China, in 2017. Phylogenetic analyses demonstrated that the hemagglutinin (HA) gene of HB95 is closely related to those of HB93 and human-origin H7N9 viruses, and that the neuraminidase (NA) gene of HB95 shared the highest nucleotide similarity with those of H5N6 viruses. HB95 and HB93 had binding affinity for human-like α2, 6-linked sialic acid receptors and were virulent in mice without prior adaptation. In addition, in guinea pig model, HB93 was transmissible by direct contact, but HB95 was transmissible via respiratory droplets. These results revealed the potential threat to public health posed by H7N6 influenza viruses and emphasized the need for continued surveillance of the circulation of this subtype in poultry.

Computational ghost imaging (CGI), with the advantages of wide spectrum, low cost, and robustness to light scattering, has been widely used in many applications. The key issue is long time correlations for acceptable imaging quality. To overcome the issue, we propose parallel retina-like computational ghost imaging (PRGI) method to improve the performance of CGI. In the PRGI scheme, sampling and reconstruction are carried out by using the patterns which are divided into blocks from designed retina-like patterns. Then, the reconstructed image of each block is stitched into the entire image corresponding to the object. The simulations demonstrate that the proposed PRGI method can obtain a sharper image while greatly reducing the time cost than CGI based on compressive sensing (CSGI), parallel architecture (PGI), and retina-like structure (RGI), thereby improving the performance of CGI. The proposed method with reasonable structure design and variable selection may lead to improve performance for similar imaging methods and provide a novel technique for real-time imaging applications.