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Porcine deltacoronavirus (PDCoV) and transmissible gastroenteritis coronavirus (TGEV), the two causative agents of porcine diarrhea, have been reported to be at risk of cross-species transmission, including to humans. However, the potential host range in which these two CoVs interact remains unclear. We screened 16 animal counterparts for porcine aminopeptidase N (APN), the receptor of PDCoV and TGEV, and found that APNs from eight of 17 animals could bind to the receptor-binding domains (RBDs) of PDCoV and TGEV. Furthermore, the animal APNs that could bind to the RBDs could mediate cellular infection by both viruses. Dog APN (dAPN) has been identified as the animal receptor with the highest capability to mediate the virus infection. We further resolved the complex structures of dAPN bound to the PDCoV RBD/TGEV RBD, respectively, establishing its divergent receptor-binding modes. We identified R325 of dAPN as an important residue in the PDCoV RBD-dAPN interaction, and found the central role of Q746 and T749 in dAPN in the interaction with the TGEV RBD. These findings provide the molecular basis of the potential cross-species transmission of these two porcine CoVs and shed light on future surveillance of these CoVs.

Raccoon dog was proposed as a potential host of SARS-CoV-2, but no evidence support such a notion. In our study, we investigated the binding affinities of raccoon dog ACE2 (rdACE2) to the spike (S) protein receptor binding domain (RBD) of SARS-CoV-2 prototype (PT) and its variants. It revealed that the binding affinities of RBD from SARS-CoV-2 variants were generally lower than that of the PT RBD. Through structural and functional analyses, we found amino acids H34 and M82 play pivotal roles in maintaining the binding affinity of ACE2 to different SARS-CoV-2 sub-variants. These results suggest that raccoon dogs exhibit lower susceptibility to SARS-CoV-2 compared to those animal species with a high prevalence of SARS-CoV-2 transmission.

Almost all the neutralizing antibodies targeting the receptor-binding domain (RBD) of spike (S) protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged or emerging variants, such as Omicron and its sub-variants. This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies. Here, we present one nanobody, N235, displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants, including the newly emerged Omicron and its sub-variants. Cryo-electron microscopy demonstrates N235 binds a novel, conserved, cryptic epitope in the N-terminal domain (NTD) of the S protein, which interferes with the RBD in the neighboring S protein. The neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S complex. Furthermore, a nano-IgM construct (MN235), engineered by fusing N235 with the human IgM Fc region, displays prevention via inducing S1 shedding and cross-linking virus particles. Compared to N235, MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in vitro. The intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo, suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.

Background The Tibial dyschondroplasia (TD) in fast-growing chickens is mainly caused by improper blood circulation. The exact mechanism underlying angiogenesis and vascularization in tibial growth plate of broiler chickens remains unclear. Therefore, this research attempts to study genes involved in the regulation of angiogenesis in chicken red blood cells. Twenty-four broiler chickens were allotted into a control and thiram (Tetramethyl thiuram disulfide) group. Blood samples were collected on day 2, 6 (8- and 14-days old chickens) and 15 (23 days old chickens). Results Histopathology and hematoxylin and eosin (H&E) results showed that angiogenesis decreased on the 6th day of the experiment but started to recover on the 15th day of the experiment. Immunohistochemistry (IHC) results confirmed the expressions of integrin alpha-v precursor (ITGAV) and clusterin precursor (CLU). Transcriptome sequencing analysis evaluated 293 differentially expressed genes (DEGs), of which 103 up-regulated genes and 190 down-regulated genes were enriched in the pathways of neuroactive ligand receptor interaction, mitogen-activated protein kinase (MAPK), ribosome, regulation of actin cytoskeleton, focal adhesion, natural killer cell mediated cytotoxicity and the notch signalling pathways. DEGs ( n  = 20) related to angiogenesis of chicken erythrocytes in the enriched pathways were thromboxane A2 receptor ( TBX A2 R ) , interleukin-1 receptor type 1 precursor ( IL 1 R 1) , ribosomal protein L17 ( RP L17) , integrin beta-3 precursor ( ITG B3) , ITG AV , integrin beta-2 precursor ( ITG B2) , ras-related C3 botulinum toxin substrate 2 ( RAC 2) , integrin alpha-2 ( ITG A2) , IQ motif containing GTPase activating protein 2 ( IQGAP 2) , ARF GTPase-activating protein ( GIT 1) , proto-oncogene vav ( VAV 1) , integrin alpha-IIb-like ( ITG A5) , ras-related protein Rap-1b precursor ( RAP 1B) , tyrosine protein kinase Fyn-like ( FYN ) , tyrosine-protein phosphatase non-receptor type 11 ( PTPN 11) , protein patched homolog 1 ( PTCH 1) , nuclear receptor corepressor 2 ( NCOR 2) and mastermind like protein 3 ( MAML 3) selected for further confirmation with qPCR. However, commonly DEGs were sarcoplasmic/endoplasmic reticulum calcium ATPase 3 ( ATP 2A3), ubiquitin-conjugating enzyme E2 R2 ( UBE 2 R 2), centriole cilia and spindle-associated protein ( CCSAP ), coagulation factor XIII A chain protein ( F 13A1), shroom 2 isoform X6 ( SHROOM 2), ras GTPase-activating protein 3 ( RAS A3) and CLU . Conclusion We have found potential therapeutic genes concerned to erythrocytes and blood regulation, which regulated the angiogenesis in thiram induced TD chickens. This study also revealed the potential functions of erythrocytes. Graphical abstract 1. Tibial dyschondroplasia (TD) in chickens were more on day 6, which started recovering on day 15. 2. The enriched pathway observed in TD chickens on day 6 was ribosome pathway, on day 15 were regulation of actin cytoskeleton and focal adhesion pathway. 3. The genes involved in the ribosome pathways was ribosomal protein L17 ( RP L17). regulation of actin cytoskeleton pathway were Ras-related C3 botulinum toxin substrate 2 ( RAC2 ), Ras-related protein Rap-1b precursor ( RAP 1B), ARF GTPase-activating protein ( GIT 1), IQ motif containing GTPase activating protein 2 ( IQGAP 2), Integrin alpha-v precursor ( ITG AV), Integrin alpha-2 ( ITG A2), Integrin beta-2 precursor ( ITG B2), Integrin beta-3 precursor ( ITG B3), Integrin alpha-IIb-like ( ITG A5). Focal adhesion Proto-oncogene vav (Vav-like), Tyrosine-protein kinase Fyn-like ( FYN ).

Background Tibial dyschondroplasia (TD) is a bone disorder in which dead chondrocytes accumulate as a result of apoptosis and non-vascularization in the tibial bone of broiler chickens. The pathogenicity of TD is under extensive research but is yet not fully understood. Several studies have linked it to apoptosis and non-vascularization in the tibial growth plate (GP). We conceived the idea to find the differentially expressed genes (DEGs) in chicken erythrocytes which vary in expression over time using a likelihood-ratio test (LRT). Thiram was used to induce TD in chickens, and then injected Ex-FABP protein at 0, 20, and 50 μg . kg -1 to evaluate its therapeutic effect on 30 screened immunity and angiogenesis-related genes using quantitative PCR (qPCR). The histopathology was also performed in TD chickens to explore the shape, circularity, arrangements of chondrocytes and blood vessels. Results Clinical lameness was observed in TD chickens, which decreased with the injection of Ex-FABP. Histopathological findings support Ex-FABP as a therapeutic agent for the morphology and vascularization of affected chondrocytes in TD chickens. qPCR results of 10 immunity ( TLR 2, TLR 3, TLR 4, TLR 5, TLR 7, TLR 15, IL -7, MyD 88, MHC II, and TRAF 6) and 20 angiogenesis-related genes ( ITGAV , ITGA 2, ITGB 2, ITGB 3, ITGA 5, IL1R 1, TBXA2 R, RPL 17, F13A 1, CLU , RAC 2, RAP1 B, GIT 1, FYN , IQGAP 2, PTCH 1, NCOR 2, VAV-like , PTPN 11, MAML 3) regulated when Ex-FABP is injected to TD chickens. Conclusion Immunity and angiogenesis-related genes can be responsible for apoptosis of chondrocytes and vascularization in tibial GP. Injection of Ex-FABP protein to thiram induced TD chickens decrease the chondrocytes damage and improves vascularization.

The green synthesis of silver nanoparticles (SNPs) using medicinal plants provides a sustainable and eco-friendly approach to nanoparticle production with promising biomedical potential. In this study, Ricinus communis and Aloe barbadensis aqueous leaf extracts were employed as reducing and stabilizing agents to synthesize R. communis SNPs (RcSNPs) and A. barbadensis SNPs (AbSNPs). The nanoparticles were characterized using ultraviolet–visible spectroscopy, dynamic light scattering, Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, and differential scanning calorimetry to evaluate their physicochemical and thermal properties. RcSNPs and AbSNPs were predominantly spherical, with average sizes of 15–20 nm and 23–28 nm, respectively, and exhibited stability up to ~90 °C. Biological evaluations demonstrated potent antimicrobial, antioxidant, anti-inflammatory, anti-tyrosinase, and cytotoxic activities. Notably, RcSNPs and AbSNPs induced apoptosis through mitochondrial pathway modulation and showed superior cytotoxicity compared to crude plant extracts and several previously reported SNPs. These findings indicate that phytochemical-mediated SNPs not only provide a green route of synthesis but also exhibit multifunctional bioactivities, which may support their potential applications as antimicrobial, antioxidant, depigmenting, and anticancer agents in biomedical and pharmaceutical fields.

The 1957 H2N2 influenza pandemic virus [A(H2N2)pdm1957] has disappeared from humans since 1968, while H2N2 avian influenza viruses (AIVs) are still circulating in birds. It is necessary to reveal the recurrence risk and potential cross-species infection of these AIVs from avian to mammals. We find that H2 AIVs circulating in domestic poultry in China have genetic and antigenic differences compared to the A(H2N2)pdm1957. One H2N2 AIV has a dual receptor-binding property similar to that of the A(H2N2)pdm1957. Molecular and structural studies reveal that the N144S, and N144E or R137M substitutions in hemagglutinin (HA) enable H2N2 avian or human viruses to bind or preferentially bind human-type receptor. The H2N2 AIV rapidly adapts to mice (female) and acquires mammalian-adapted mutations that facilitated transmission in guinea pigs and ferrets (female). These findings on the receptor-binding, infectivity, transmission, and mammalian-adaptation characteristics of H2N2 AIVs provide a reference for early-warning and prevention for this subtype. The authors identify one emerging H2N2 AIV, reveal the molecular basis of human-type receptor binding of the H2N2 AIV and pandemic strains, and evaluate the public risk of H2N2 AIV by its infection, transmission and mammalian-adaptation features.

Pseudorabies virus (PRV) variants have caused substantial economic losses in the swine industry in China since 2011. To surveil the genetic variation in PRV field strains, here, two novel variant strains of PRV were isolated from Shanxi Province in central China and were designated SX1910 and SX1911. To identify the genetic characteristics of the two isolates, their complete genomes were sequenced, and phylogenetic analysis and sequence alignment revealed that field PRV variants have undergone genetic variations; notably, the protein-coding sequences UL5, UL36, US1 and IE180 exhibited extensive variation and contained one or more hypervariable regions. Furthermore, we also found that the glycoproteins gB and gD of the two isolates had some novel amino acid (aa) mutations. Importantly, most of these mutations were located on the surface of the protein molecule, according to protein structure model analysis. We constructed a mutant virus of SX1911 with deletion of the gE and gI genes via CRISPR/Cas9. When tested in mice, SX1911-ΔgE/gI-vaccinated mice were protected within a comparable range to Bartha-K61-vaccinated mice. Additionally, a higher dose of inactivated Bartha-K61 protected the mice from lethal SX1911 challenge, while a lower neutralization titer, higher viral load and more severe microscopic lesions were displayed in Bartha-K61-vaccinated mice. These findings highlight the need for continuous monitoring of PRV and novel vaccine development or vaccination program design for PRV control in China.

PCR-based techniques play a crucial role in genotyping and genetic screening in fungal biology. Rapid access to nucleic acids for these reactions can significantly improve the efficiency of fungal analysis, especially when multiple samples need to be tested. In this study, we introduced a simple and rapid method for detecting small amounts of fungal DNA or RNA, named the One-Step method, and confirmed its applicability across various experimental scenarios for fungal detection. The method involves scraping a small quantity of spores or mycelium into sterile water, followed by heat shock, vortexing, and centrifugation to obtain a supernatant that serves as a template for the PCR reaction. Notably, nucleic acids were successfully extracted using the One-Step method from four different genera of fungi-Neurospora crassa, Aspergillus fumigatus, Fusarium oxysporum, and Schizosaccharomyces pombe, as well as from two mycovirus-containing strains, yielding reliable results in PCR identification. However, the nucleic acids of Cryptococcus neoformans were not successfully extracted using the One-Step method, possibly due to the challenge of cleaving its polysaccharide capsule. Taken together, the One-Step method significantly reduces nucleic acids extraction time while enhancing strain screening efficiency in four different fungi, indicating a broad applicability in fungal biology.

(1) The aim of this study was to elucidate the role of the Gallus gallus avian β-defensin 11 (AvBD11) in the immune response induced by the avian influenza virus H9N2. (2) AvBD11 was expressed using E. coli, and the effects of different concentrations of AvBD11 on cytokine expression in the ex vivo and in vivo erythrocytes of chickens infected with the avian influenza subtype H9N2 were detected by using fluorescence quantification. (3) The results showed that cytokine expression varied among the test groups compared to the control group in the in vitro assay at 2, 6, and 10 h. Lipopolysaccharide induced TNF factor (LITAF) and Interferon-γ (IFN-γ) were significantly increased in the AvBD11 group with the addition of the final concentration of 15 μg/mL at 6 h. At 10 h, Interleukin-1β (IL-1β) and IFN-γ were both more significantly increased in the 15 and 10 μg/mL groups than in the H9N2 group alone. In the in vivo test, IFN-γ and Interleukin-10 (IL-10) were significantly increased in the high-dose group than in the H9N2 group at 3 d and 7 d. (4) In conclusion, the ability of AvBD11 to induce the expression of more cytokines by chicken erythrocytes in a short period of time suggests that it is not only an antimicrobial peptide but also a possible immunomodulator.