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Scabies is a common parasitic disease in many mammalian species, caused by the infestation of Sarcoptes scabiei. There is no consistent conclusion on whether Sarcoptes mites from different hosts or geographic locations have apparent genetic divergence. In this study, we collected and morphologically identified S. scabiei from Chinese serow and goral, and we described the genetic diversity of S. scabiei and other mites based on phylogenetic analyses of the ITS2 and cox1 sequence fragments, including data available in GenBank. The mites isolated from Chinese serow and goral were S. scabiei, and they were morphologically similar. The phylogenetic trees and haplotype networks showed that S. scabiei from other locations worldwide did not cluster according to host divergence or geographical distribution. Additionally, the Fst values were - 0.224 to 0.136 and - 0.045 to 1 between S. scabiei from different hosts, including humans and domestic and wild animals, based on partial ITS and cox1 sequences. Worldwide S. scabiei samples formed three clusters (with H2, H5, and H12 at their centers) in the ITS and one cluster (with C9 at the center) in the cox1 haplotype phylogenetic network. The S. scabiei collected from Chinese serow and goral were morphologically similar and had the same genotype. A study on the genetic characteristics of S. scabiei from Chinese serow and goral together with other mites from different hosts and geographic locations around the world showed no obvious divergence. These findings indicated that scabies likely is a zoonotic disease and that the global prevalence of scabies is probably related to the worldwide trade of domestic animals.

Background: Vector-borne flaviviruses, including tick-borne encephalitis virus (TBEV), Zika virus (ZIKA), West Nile virus (WNV), yellow fever virus (YFV), dengue virus (DENV), and Japanese encephalitis virus (JEV), pose a growing threat to public health worldwide, and have evolved complex mechanisms to overcome host antiviral innate immunity. However, the underlying mechanisms of flavivirus structural proteins to evade host immune response remain elusive. Results: We show that TBEV structural protein, pre-membrane (prM) protein, could inhibit type I interferon (IFN-I) production. Mechanically, TBEV prM interacted with both MDA5 and MAVS and interfered with the formation of MDA5-MAVS complex, thereby impeding the nuclear translocation and dimerization of IRF3 to inhibit RLR antiviral signaling. ZIKA and WNV prM was also demonstrated to interact with both MDA5 and MAVS, while dengue virus serotype 2 (DENV2) and YFV prM associated only with MDA5 or MAVS to suppress IFN-I production. In contrast, JEV prM could not suppress IFN-I production. Overexpression of TBEV and ZIKA prM significantly promoted the replication of TBEV and Sendai virus. Conclusion: Our findings reveal the immune evasion mechanisms of flavivirus prM, which may contribute to understanding flavivirus pathogenicity, therapeutic intervention and vaccine development.

SARS-CoV-2, the causative agent of the COVID-19 pandemic, undergoes continuous evolution, highlighting an urgent need for development of novel antiviral therapies. Here we show a quantitative mass spectrometry-based succinylproteomics analysis of SARS-CoV-2 infection in Caco-2 cells, revealing dramatic reshape of succinylation on host and viral proteins. SARS-CoV-2 infection promotes succinylation of several key enzymes in the TCA, leading to inhibition of cellular metabolic pathways. We demonstrated that host protein succinylation is regulated by viral nonstructural protein (NSP14) through interaction with sirtuin 5 (SIRT5); overexpressed SIRT5 can effectively inhibit virus replication. We found succinylation inhibitors possess significant antiviral effects. We also found that SARS-CoV-2 nucleocapsid and membrane proteins underwent succinylation modification, which was conserved in SARS-CoV-2 and its variants. Collectively, our results uncover a regulatory mechanism of host protein posttranslational modification and cellular pathways mediated by SARS-CoV-2, which may become antiviral drug targets against COVID-19.

Several nairo-like viruses have been discovered in ticks in recent years, but their relevance to public health remains unknown. Here, we found a patient who had a history of tick bite and suffered from a febrile illness was infected with a previously discovered RNA virus, Beiji nairovirus (BJNV), in the nairo-like virus group of the order Bunyavirales. We isolated the virus by cell culture assay. BJNV could induce cytopathic effects in the baby hamster kidney and human hepatocellular carcinoma cells. Negative-stain electron microscopy revealed enveloped and spherical viral particles, morphologically similar to those of nairoviruses. We identified 67 patients as BJNV infection in 2017–2018. The median age of patients was 48 years (interquartile range 41–53 years); the median incubation period was 7 days (interquartile range 3–12 days). Most patients were men (70%), and a few (10%) had underlying diseases. Common symptoms of infected patients included fever (100%), headache (99%), depression (63%), coma (63%), and fatigue (54%), myalgia or arthralgia (45%); two (3%) patients became critically ill and one died. BJNV could cause growth retardation, viremia and histopathological changes in infected suckling mice. BJNV was also detected in sheep, cattle, and multiple tick species. These findings demonstrated that the newly discovered nairo-like virus may be associated with a febrile illness, with the potential vectors of ticks and reservoirs of sheep and cattle, highlighting its public health significance and necessity of further investigation in the tick-endemic areas worldwide.

The Ascaridoidea family and Heterakoidea family are the most common and typical representative of large parasites. Although our understanding of these parasites' diversity has expanded by analyses of some mitochondrial genes, there is limited information on these species' evolutionary rates. Here we determined ten complete mitogenome sequences of five subfamilies of Ascaridoidea and one subfamily of Heterakoidea. The phylogenetic tree divided the Ascaridoidea into six monophyletic major clades, and the divergence time of Heterakoidea family and Ascaridoidea family can be placed during the early Carboniferous Period (300-360 Mya). The reconstruction of the ancestral state showed that the gene orders of all species in Ascaridoidea were conserved, and the Heterakoidea had obvious genome rearrangement. The conserved blocks between them were divided into five and the main types are tandem-duplication/random loss (TDRL). These results will help to better understand the gene rearrangements and evolutionary position of ascaris species.

The recent boom of autonomous driving nowadays has made object detection in traffic scenes a hot topic of research. Designed to classify and locate instances in the image, this is a basic but challenging task in the computer vision field. With its powerful feature extraction abilities, which are vital for object detection, deep learning has expanded its application areas to this field during the past several years and thus achieved breakthroughs. However, even with such powerful approaches, traffic scenarios have their own specific challenges, such as real-time detection, changeable weather, and complex lighting conditions. This survey is dedicated to summarizing research and papers on applying deep learning to the transportation environment in recent years. More than 100 research papers are covered, and different aspects such as key generic object detection frameworks, categorized object detection applications in traffic scenario, evaluation metrics, and classified datasets are included. Some open research fields are also provided. We believe that it is the first survey focusing on deep learning-based object detection in traffic scenario.

The overall infection rate of Pentatrichomonas hominis in Siberian tigers in northeast China is 31.3%. All the P. hominis identified in Siberian tigers belonged to genotype CC1.

Helminth diseases have long been a threat to the health of humans and animals. Roundworms are important organisms for studying parasitic mechanisms, disease transmission and prevention. The study of parasites in the giant panda is of importance for understanding how roundworms adapt to the host. Here, we report a high-quality chromosome-scale genome of Baylisascaris schroederi with a genome size of 253.60 Mb and 19,262 predicted protein-coding genes. We found that gene families related to epidermal chitin synthesis and environmental information processes in the roundworm genome have expanded significantly. Furthermore, we demonstrated unique genes involved in essential amino acid metabolism in the B. schroederi genome, inferred to be essential for the adaptation to the giant panda-specific diet. In addition, under different deworming pressures, we found that four resistance-related genes (glc-1, nrf-6, bre-4 and ced-7) were under strong positive selection in a captive population. Finally, 23 known drug targets and 47 potential drug target proteins (essential homologues linked to lethal phenotypes) were identified. The genome provides a unique reference for inferring the early evolution of roundworms and their adaptation to the host. Population genetic analysis and drug sensitivity prediction provide insights revealing the impact of deworming history on population genetic structure of importance for disease prevention.

The Amur leopard, one of nine recently recognized subspecies of leopard, is still the most threatened by a stochastic procession of extinction. Evaluation of the potential danger to the conservation of the Amur leopard originating from disease urgently needs to be studied. Unfortunately, research on the potential risk to Amur leopards caused by disease is rare. In terms of parasitic diseases that affect this species, even basic data for parasitic fauna are absent. The aim of this study is to acquire this knowledge to improve the general understanding of Amur leopard parasites. Seven parasite species, including 3 nematodes (Toxocara cati, a capillarid-type parasite, and a Metastrongyloidea-type parasite), 2 cestodes (Spirometra sp. and Taenia sp.), 1 trematode (Paragonimus sp.), and 1 protozoan (Cystoisospora felis), were found in this research. Toxocara cati occurred most frequently, followed by Spirometra sp.

Mesenchymal stem cells (MSCs) are multipotent adult stem cells and can be isolated from many tissues of the body. Due to their potentials to treat various diseases and be applied in animal breeding, MSCs have been isolated and identified regarding their biological properties. Common hippos (Hippopotamus amphibius) are a vulnerable species and yet the cryopreservation of their genetic materials is scare. In this study, we successfully established two MSC lines (UC-MSCs and AT-MSCs) from the umbilical cord and adipose tissue of a neonatal common hippo and comparatively described their features. Both UC-MSCs and AT-MSCs showed fibroblastoid morphology and could be continuously passaged for over 17 passages without dramatic signs of senescence. The cell cultures had normal chromosome composition, say, 17 pairs of autosomes and 1 pair of X chromosomes. UC-MSCs and AT-MSCs displayed similar gene expression profiles. They were positive for CD45, CD73, CD90 and CD105 and negative for HLA-DR. They demonstrated stemness maintenance by expression of classical stem cell markers. UC-MSCs and AT-MSCs manifested different differentiation potentials into other cell lineages. In summary, these two cell lines demonstrated the essential properties of mesenchymal stem cells and might play a role in the future research.

In recent years, the emerging highly pathogenic avian influenza (HPAI) A(H5N8) virus has been reported with features of widely spread, an expanding host range, and cross-species transmission, attracting wide attention. The domestic duck plays a major role in the epidemiological cycle of the HPAI H5N8 virus, but little is known concerning innate immune responses during influenza infection in duck species. In this study, we used two wild-bird-origin viruses, H5N8 and H4N6, to conduct duck infection experiments, and detect the load of the two viruses, and retinoic acid-inducible gene I (RIG-I) and interferon β (IFN-β) in the host’s natural immune response. Through comparison, it is found that the expression levels of RIG-I and IFN-β are both fluctuating. The innate immunity starts rapidly within 6 h after infection and is inhibited by the virus to varying degrees. The expression of RIG-I and IFN-β decreased on 1–2 days post-infection (dpi). The HPAI H5N8 virus has a stronger inhibitory effect on RIG-I than the low pathogenic avian influenza (LPAI) H4N6 virus and is the strongest in the lungs. After infection with HPAI H5N8 virus, 2 dpi, viral RNA replicates in large amounts in the lungs. It has been proven that RIG-I and IFN-β play an important role in the innate immune response of ducks to HPAI H5N8 virus infection, especially in the lungs. The main battlefield of RIG-I and IFN-β after infection with the LPAI H4N6 virus is in the rectum. Both viruses have been effectively controlled after 7 dpi. These results will help to understand the transmission mechanisms of avian influenza virus in wild ducks and help effectively prevent and control avian influenza.

Highly pathogenic influenza A(H5N8) viruses have caused several worldwide outbreaks in birds and are able cross the species barrier to infect humans, posing a substantial threat to public health. After the first detection of H5N8 viruses in deceased swans in Inner Mongolia, we performed early warning and active monitoring along swan migration routes in central China. We isolated and sequenced 42 avian influenza viruses, including 40 H5N8 viruses, 1 H5N2 virus, and 1 H9N2 virus, in central China. Our H5N8 viruses isolated in swan stopover sites and wintering grounds showed high nucleotide homologies in the whole genome, revealing a common evolutionary source. Phylogenetic analysis revealed that the H5 viruses of clade 2.3.4.4b prevalent in 2020 have further diverged into two sub-clades: b1 and b2. The phylogeographic analysis also showed that the viruses of sub-clade b2 most likely originated from poultry in Russia. Notably, whooper swans were found to be responsible for the introduction of sub-clade b2 viruses in central China; whooper and tundra swans play a role in viral spread in the Yellow River Basin and the Yangtze River Basin, respectively. Our findings highlight swans as an indicator species for transborder spreading and monitoring of the H5N8 virus.

A 2-year surveillance study of influenza A viruses in migratory birds was conducted to understand the subsequent risk during the migratory seasons in Dandong Yalu River Estuary Coastal Wetland National Nature Reserve, Liaoning Province, China, a major stopover site on the East Asian-Australasian flyway. Overall, we isolated 27 influenza A viruses with multiple subtypes, including H3N8 (n=2), H4N6 (n=2), H4N7 (n=2), H7N4 (n=9), H7N7 (n=1), H10N7 (n=7), and H13N6 (n=4). Particularly, a novel reassortant influenza A(H7N4) virus was first identified in a woman and her backyard poultry flock in Jiangsu Province, China, posing a serious threat to public health. Here, we describe the genetic characterization and pathogenicity of the nine influenza A(H7N4) isolates. Phylogenetic analysis indicated that complex viral gene flow occurred among Asian countries. We also demonstrated a similar evolutionary trajectory of the surface genes of the A(H7N4) isolates and Jiangsu human-related A(H7N4) viruses. Our A(H7N4) isolates exhibited differing degrees of virulence in mice, suggesting a potential risk to other mammalian species, including humans. We revealed multiple mutations that might affect viral virulence in mice. Our report highlights the importance and needs for the long-term surveillance of avian influenza virus in migratory birds, combined with domestic poultry surveillance along migratory routes and flyways, and thereby develop measures to manage potential health threats. Importance The H7 subtype avian influenza viruses, such as H7N2, H7N3, H7N4, H7N7, and H7N9, were documented being capable of infecting humans, and the H7 subtype low pathogenic avian influenza viruses are capable of mutating into highly pathogenic avian influenza; therefore, they pose a serious threat to public health. Here, we investigated the evolutionary history, molecular characteristics, and pathogenicity of shorebird-origin influenza A(H7N4) viruses, showing a similar evolutionary trajectory with Jiangsu human A(H7N4) viruses in HA and NA genes. Moreover, our isolates exhibited variable virulence (including moderate virulence) in mice, suggesting a potential risk to other mammalian species, including humans.

Background The evolution of parasites is often directly affected by the host's environment. Studies on the evolution of the same parasites in different hosts are extremely attractive and highly relevant to our understanding of divergence and speciation. Methods Here we performed whole genome sequencing of Parascaris univalens from different Equus hosts (horses, zebras and donkeys). Phylogenetic and selection analysis was performed to study the divergence and adaptability of P. univalens. Results At the genetic level, multiple lines of evidence support that P. univalens were mainly separated into two clades (Horse-derived and Zebra & Donkey-derived). This divergence began at 300-1000 years ago, and we found that most of the key enzymes related to glycolysis were under strong positive selection in zebra & donkey-derived roundworms, but lipid related metabolism system was under positive selection in the horse-derived roundworms, indicating that the adaptive evolution of metabolism may drive the divergence in past few centuries. In addition, we found that some drug-related genes have a significantly higher degree of selection in different populations. Conclusions This work reports evidence that the host’s diet drives the divergence of roundworms for the first time, and also supports that divergence is a continuous and dynamic process, and continuous monitoring of the effects of differences in nutritional and drug history on rapid evolution of roundworms are conducive to further understanding host-parasite interactions.

Background The evolution of parasites is often directly affected by the host's environment. Studies on the evolution of the same parasites in different hosts are of great interest and are highly relevant to our understanding of divergence. Methods Here we performed whole-genome sequencing of Parascaris univalens from different Equus hosts (horses, zebras and donkeys). Phylogenetic and selection analyses were performed to study the divergence and adaptability of P. univalens. Results At the genetic level, multiple lines of evidence indicate that P. univalens is mainly separated into two clades (horse-derived and zebra & donkey-derived). This divergence began 300–1000 years ago, and we found that most of the key enzymes related to glycolysis were under strong positive selection in zebra & donkey-derived roundworms, whereas the lipid-related metabolic system was under positive selection in horse-derived roundworms, indicating that the adaptive evolution of metabolism has occurred over the past few centuries. In addition, we found that some drug-related genes showed a significantly higher degree of selection in diverse populations. Conclusions This work reports the adaptive evolution and divergence trend of P. univalens in different hosts for the first time. Its results indicate that the divergence of P. univalens is a continuous, dynamic process. Furthermore, the continuous monitoring of the effects of differences in nutritional and drug histories on the rapid evolution of roundworms is conducive to further understanding host-parasite interactions.

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of ongoing global pandemic of COVID-19, may trigger immunosuppression in the early stage and overactive immune response in the late stage of infection; However, the underlying mechanisms are not well understood. Here we demonstrated that the SARS-CoV-2 nucleocapsid (N) protein dually regulated innate immune responses, i.e., the low-dose N protein suppressed type I interferon (IFN-I) signaling and inflammatory cytokines, whereas high-dose N protein promoted IFN-I signaling and inflammatory cytokines. Mechanistically, the SARS-CoV-2 N protein dually regulated the phosphorylation and nuclear translocation of IRF3, STAT1, and STAT2. Additionally, low-dose N protein combined with TRIM25 could suppress the ubiquitination and activation of retinoic acid-inducible gene I (RIG-I). Our findings revealed a regulatory mechanism of innate immune responses by the SARS-CoV-2 N protein, which would contribute to understanding the pathogenesis of SARS-CoV-2 and other SARS-like coronaviruses, and development of more effective strategies for controlling COVID-19.

Cryptosporidium spp. is a protozoan having the potential to cause zoonosis in humans and animals. Despite the zoonotic importance of this protozoan parasite, limited data are available about its prevalence in zoo felids in North-Eastern China. Hence, the current study was designed to determine the occurrence and molecular characterization of Cryptosporidium spp. from the fecal samples of captive zoo felids. Fecal samples (N = 244) were collected from different felids from five different zoos of North-Eastern China. 18S rRNA gene was amplified from the genomic DNA using species specific primers in nested polymerase chain reaction (nPCR) and Cryptosporidium parvum and Cryptosporidium spp. was found. The overall prevalence of Cryptosporidium was 9.43% (23/244). The 18S rRNA gene similarity analysis showed that 6 Cryptosporidium isolates were Cryptosporidium parvum and the remaining 17 Cryptosporidium isolates were resembling to a Cryptosporidium spp., which is similar to Cryptosporidium NEV10. Phylogenetic tree was constructed based on 18S rRNA of Cryptosporidium spp. The similarity of Cryptosporidium parvum was with its other isolates in China, India, Iran, Iraq, Turkey, Czech Republic, Spain and USA while Cryptosporidium NEV10 alike had a close relationship with Turkish isolates. In conclusion, Cryptosporidium was prevailing in feline animals of China zoo and zoo officials are directed to consider their control policy as it can be a cause of zoonosis.

The evolution of parasites is often directly affected by the host's environment or behavior. Studies on the evolution of the same parasites in different hosts are extremely attractive and highly relevant to our understanding of divergence and speciation. Here we presented the first molecular evidence of divergence of Equus roundworms in different hosts (horses, zebras and donkeys). At the genetic level, Equus roundworms were mainly separated into two clades (Horse-derived and Zebra & Donkey-derived). This divergence began at 600–1500 years ago, which interestingly coincided with the domestication history of horses. We found that most of the key enzymes related to glycolysis were under strong positive selection in zebra & donkey-derived roundworms, indicating that the evolution of the metabolic level was one of the main reasons for the divergence. In addition, we conducted a selective scan of resistance-related genes and found that the three populations were under different degrees of selection. This prompted us to pay attention to the possible impact of drugs on divergence, not just the drug resistance. This work supports that divergence or speciation is a continuous and dynamic process, and continuous monitoring of environmental factors is conducive to further understanding the adaptive evolution of roundworms.

Mesenchymal stem cells (MSCs) are multipotent adult stem cells and can be isolated from many tissues of the body. Due to their potentials to treat various diseases and be applied in animal breeding, MSCs have been isolated and identified regarding their biological properties. Common hippos (Hippopotamus amphibius) are a vulnerable species and yet the cryopreservation of their genetic materials is scare. In this study, we successfully established two MSC cultures (UC-MSCs and AT-MSCs) from the umbilical cord and adipose tissue of a neonatal common hippo and comparatively described their features. Both UC-MSCs and AT-MSCs showed fibroblastoid morphology and could be continuously passaged for over 17 passages without dramatic signs of senescence. The cell cultures had normal chromosome composition, say, 17 pairs of autosomes and 1 pair of X chromosomes. UC-MSCs and AT-MSCs displayed similar gene expression profiles. They were positive for CD34, CD45, CD73, CD90 and CD105 and negative for HLA-DR. They demonstrated stemness maintenance by expression of classical stem cell markers. UC-MSCs and AT-MSCs manifested different differentiation potentials into other cell lineages. In summary, these two cell cultures demonstrated the essential properties of mesenchymal stem cells and might play a role in the future research.

The blue fox (Vulpes lagopus), a fur-bearing animal, is an important component of the breeding industry in China. Semen quality is a key factor for the reproductive process and the breeding effectiveness of the farmed blue fox. However, bacterial contamination in semen samples utilized in artificial fertilization is very common. The β-defensins, a class of important antimicrobial peptides in mammals, could protect the reproductive system of male animals from bacterial invasion, maintain the stability of the genital tract microenvironment and improve semen quality. In this study, molecular cloning and bioinformatics analysis were conducted to analyze the protein structure and function of blue fox β-defensin 108 (Vulpes lagopus beta-defensin 108, vBD108) and 122 (Vulpes lagopus beta-defensin 122, vBD122). To evaluate the bacteriostatic effect of recombinant vBDs (Vulpes lagopus beta-defensins) protein, varying concentrations (0, 25, 50, 100, 200 µg/mL) were taken to evaluate the effects on Escherichia coli and Staphylococcus aureus at different times (0, 2, 4, 6, 8, 12 h). The results showed that vBD108 and vBD122 existed in different forms in protein structure and had antibacterial activity. Both proteins, at 50 µg/mL, had efficacious bacteriostatic activity. This study shows that recombinant vBD108 and vBD122 proteins have good antibacterial activity in vitro. This implies a potential role in improving semen quality and hygienic measures in the process of artificial insemination as an extender of semen dilution with antibacterial activity.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen of current COVID-19 pandemic, and insufficient production of type I interferon (IFN-I) is associated with the severe forms of the disease. Membrane (M) protein of SARS-CoV-2 has been reported to suppress host IFN-I production, but the underlying mechanism is not completely understood. In this study, SARS-CoV-2 M protein was confirmed to suppress the expression of IFNβ and interferon-stimulated genes induced by RIG-I, MDA5, IKKϵ, and TBK1, and to inhibit IRF3 phosphorylation and dimerization caused by TBK1. SARS-CoV-2 M could interact with MDA5, TRAF3, IKKϵ, and TBK1, and induce TBK1 degradation via K48-linked ubiquitination. The reduced TBK1 further impaired the formation of TRAF3–TANK–TBK1-IKKε complex that leads to inhibition of IFN-I production. Our study revealed a novel mechanism of SARS-CoV-2 M for negative regulation of IFN-I production, which would provide deeper insight into the innate immunosuppression and pathogenicity of SARS-CoV-2.

During a helminthological study of waterfowl in China, a new species (Cloacotaenia cygnimorbus sp. nov.) of hymenolepidid cestodes (tapeworm) was found in the small intestine of whooper swan (Cygnus cygnus, Linnaeus, 1758). The rudimentary rostellum and four unarmed muscular suckers, proglottids with distinct craspedote and three spherical testes were coincident with the characters of Cloacotaenia or Hymenolepis, but phylogenetic analysis of 28S rRNA and cox1 gene revealed that the new species is Cloacotaenia rather than Hymenolepis. Its morphology was also clearly differentiated from C. megalops in the arrangement of its testes in a triangle instead of in line and the cirrus unarmed rather than spined. Compared with C. megalops, the new species has more elongated neck, much larger mature proglottids and much smaller testes, cirrus sac, ovary, vitellarium and uterine proglottid. In addition, it infected the host intestine not the cloacae. Phylogenetic analysis of cox1 gene of the new species shows that it had a level of sequence variation (10.52–23.06%) with the sequences of C. megalops. The considerable morphological and molecular differences between those two parasites support C. cygnimorbus sp. nov. as a new species.

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing global pandemic of COVID-19, may trigger immunosuppression in the early stage and a cytokine storm in the late stage of infection, however, the underlying mechanisms are not well understood. Here we demonstrated that the SARS-CoV-2 nucleocapsid (N) protein dually regulated innate immune responses, i.e., the low-dose N protein suppressed type I interferon (IFN-I) signaling and inflammatory cytokines, whereas high-dose N protein promoted IFN-I signaling and inflammatory cytokines. Mechanistically, the SARS-CoV-2 N protein interacted with the tripartite motif protein 25 (TRIM25), thereby dually regulating the phosphorylation and nuclear translocation of IRF3, STAT1 and STAT2. Additionally, low-dose N protein combined with TRIM25 could suppress retinoic acid-inducible gene I (RIG-I) ubiquitination and activation. Our findings revealed a regulatory mechanism of innate immune responses by the SARS-CoV-2 N protein, which would contribute to understanding the pathogenesis of SARS-CoV-2 and other SARS-like coronaviruses, and development of more effective strategies for controlling COVID-19.

Background Fecundity is important for farm blue fox (Vulpes lagopus), who with asthenospermia have be a problem in some of farms in China. A key symptom of asthenospermia is decreased sperm motility. The decreased secreting beta-defensin108 (vBD108) of blue fox is speculated be related to asthenospermia. To clarify this idea, the mRNA expression of vBD108 in testis and epididymis of blue foxes with asthenospermia were detected and compared to the healthy one. The antibody was prepared and analyzed by immunohistochemistry. Results The vBD108 in testis and epididymis was found both in blue fox with asthenospermia and healthy group by the method of immunohistochemistry. The expression of vBD108 mRNA in testes (P P Conclusions These results suggested that vBD108 deficiency may related to blue fox asthenospermia. Meanwhile, the study on the blue fox vBD108 provides a hopeful direction to explore the pathogenesis of blue fox asthenospermia in the future.