The antioxidant activity and metabolomic analysis of the supernatant of Streptococcus alactolyticus strain FGM.

Strain-specific probiotics can present antioxidant activity and reduce damage caused by oxidation. Streptococcus alactolyticus strain FGM (S. alactolyticus strain FGM) isolated from the chicken cecum shows potential probiotic properties which have been previously demonstrated. However, the antioxidant properties of S. alactolyticus strain FGM remain unknown. In this view, cell-free supernatant (CFS), intact cells (IC) and intracellular extracts (CFE) of strain FGM and 3 strains of Lactobacillus (LAB) were prepared, and their scavenging capacities against DPPH, hydroxyl radicals and linoleic acid peroxidation inhibitory were compared in this study. The effects of strain FGM cell-free supernatant (FCFS) on NO production, activity of SOD and GSH-Px in RAW264.7 cells and LPS-induced RAW264.7 cells were analyzed. The metabolites in the supernatant were quantitated by N300 Quantitative Metabolome. It was shown that the physicochemical characteristics of CFS to scavenge DPPH, hydroxyl radicals, and linoleic acid peroxidation inhibitory were significantly stronger than that of IC and CFE in the strain FGM (P < 0.05), respectively 87.12% ± 1.62, 45.03% ± 1.27, 15.63% ± 1.34. FCFS had a promotional effect on RAW264.7 cells, and significantly elevated SOD and GSH-Px activities in RAW264.7 cells. 25 µL FCFS significantly promoted the proliferation of RAW264.7 cells induced by LPS, increased the activities of SOD and GSH-PX, and decreased the release of NO. Furthermore, among the differential metabolites of FCFS quantified by N300, 12 metabolites were significantly up-regulated, including lactic acid, indole lactic acid, linoleic acid, pyruvic acid etc., many of which are known with antioxidant properties. In conclusion, FCFS had good antioxidant properties and activity, which can be attributed to metabolites produced from strain FGM fermentation. It was further confirmed that S. alactolyticus strain FGM and its postbiotic have potential probiotic properties and bright application prospects in livestock and poultry breeding.

A randomized double-blind clinical trial: Comparison of oclacitinib with a traditional Chinese herbal medicine product (Dihuang Guiqin capsule) in the treatment of canine atopic dermatitis.

Canine atopic dermatitis (cAD) is a common chronic inflammatory skin disease, which seriously affects the quality of life for both dogs and their owners. Currently, the common therapeutic drugs in the clinic have disadvantages such as obvious adverse effects and high prices. Traditional Chinese herbal medicine (TCHM) has great potential for the treatment of cAD. The aim of this study is to compare the effects of different doses of the TCHM product (Dihuang Guiqin capsule) and oclacitinib in the treatment of cAD through a randomized, double-blind trial. Sixty dogs diagnosed with AD were randomly and evenly divided into four groups (n = 15). The TCHM treatment group consisted of three subgroups that received three different oral doses (20, 40, and 60 mg/kg BW), while the control group received 0.5 mg/kg BW of oclacitinib. Each group was administered twice daily for 14 consecutive days. The results showed that both TCHM and oclacitinib significantly improved cAD-induced itching (evaluated by pVAS) and skin lesions (evaluated by CADESI-04), while interleukin 31 (IL-31) concentrations decreased significantly (P < 0.05) and serum biochemical indicators returned to normal. In particular, The therapeutic effects of TCHM medium- and high-dose groups were similar to those of oclacitinib (P > 0.05). The preliminary recommended dose of Dihuang Guiqin capsule for the treatment of cAD has been determined to be 40-60 mg/kg BW twice daily for 14 consecutive days, which can be reduced to once daily as appropriate. Dihuang Guiqin capsule was safe and well tolerated, which may be a new option for the treatment of cAD.

Correlation Between MicroRNA by Extracellular Vesicle Mediated and Antiviral Effects of Interferon Omega in Feline Peripheral Blood.

Feline interferon omega (IFN-ω) has been proven to have high antiviral activity; however, its in-depth antiviral effects remain unknown. Extracellular vesicles (EVs) have been demonstrated to participate in the regulation of the immune response pathway for the body through various active substances, especially through the microRNA (miRNA) carried by them. In this study, we isolated EVs from feline peripheral blood by differential centrifugation, and further found that the content of IFN-ω in EVs increased continuously within 24 h after IFN-ω treatment, and a large number of miRNAs were significantly downregulated in EVs within 12 h after IFN-ω treatment. These significantly differentially expressed miRNAs were important for regulating changes in antiviral cytokines. This study reveals for the first time the correlation between EVs-mediated miRNA in feline peripheral blood and IFN-ω on antiviral immune response, which may provide strong data support for the development of novel antiviral nanomedicine and the research of the antiviral effects of IFN-ω.

Baicalin Protects Broilers against Avian Coronavirus Infection via Regulating Respiratory Tract Microbiota and Amino Acid Metabolism.

An increasing amount of evidence indicates that Baicalin (Bai, a natural glycosyloxyflavone compound) exhibits an antiviral effect against avian viruses. However, it remains unclear if the antiviral effect of Bai against infectious bronchitis virus (IBV) is exerted indirectly by modulating respiratory tract microbiota and/or their metabolites. In this study, we investigated the protection efficacy of Bai in protecting cell cultures and broilers from IBV infection and assessed modulation of respiratory tract microbiota and metabolites during infection. Bai was administered orally to broilers by being mixed in with drinking water for seven days. Ultimately, broilers were challenged with live IBV. The results showed that Bai treatment reduced respiratory tract symptoms, improved weight gain, slowed histopathological damage, reduced virus loads and decreased pro-inflammation cytokines production. Western blot analysis demonstrated that Bai treatment significantly inhibited Toll-like receptor 7 (TLR7), myeloid differentiation factor 88 (MyD88) and nuclear factor kappa-B (NF-κB) expression both in cell culture and cells of the trachea. Bai treatment reversed respiratory tract microbiota dysbiosis, as shown by 16S rDNA sequencing in the group of broilers inoculated with IBV. Indeed, we observed a decrease in Proteobacteria abundance and an increase in Firmicutes abundance. Metabolomics results suggest that the pentose phosphate pathway, amino acid and nicotinamide metabolism are linked to the protection conferred by Bai against IBV infection. In conclusion, these results indicated that further assessment of anti-IBV strategies based on Bai would likely result in the development of antiviral molecule(s) which can be administered by being mixed with feed or water.

Prevalence and molecular characterization of extended-spectrum ß-lactamase-producing Escherichia coli isolates from dairy cattle with endometritis in Gansu Province, China.

BACKGROUND: The present study aimed to investigate the prevalence and molecular characterization of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli) isolated from dairy cattle with endometritis in China. The prevalence of ESBL-producing E. coli in sample was detected using ChromID ESBL agar, and genotyping of the ESBL producers was performed by PCR and DNA sequencing. RESULTS: The results revealed that the proportion of positive pathogens tested was 69.76% (180/258) in samples obtained from cows diagnosed with clinical endometritis, with E. coli accounting for 170 out of the 180 positive samples. The infection rate of isolated E. coli was 39.14% (101/258), and co-infections with other pathogens were prevalent. Furthermore, among the 158 E. coli isolates, 50 strains were identified as ESBL producers, with TEM and CTX-M prevalence rates at 78.00% and 32.00%, respectively. Drug sensitivity experiments indicated that 50 isolates of ESBL- producing E. coli were multidrug resistance (MDR), with 48.0% of them exhibiting positive results for both the class 1 integron gene and five gene cassettes associated with resistance to trimethoprim (dfr1 and dfrA17) and aminoglycosides (aadA1, aadA5, and dfrA1), respectively. CONCLUSION: This investigation demonstrated a substantial prevalence and heightened level of antimicrobial resistance among ESBL-producing E. coli isolates derived from dairy cattle infected with endometritis in China.

Revealing the Effect of the [CoO]6 Microstructure in Pseudocapacitance by Controlled Delithium of LiCoO2.

Revealing the in-depth structure-property relationship and designing specific capacity electrodes are particularly important for supercapacitors. Despite many efforts made to tune the composition and electronic structure of cobalt oxide for pseudocapacitance, insight into the [CoO]6 octahedron from the microstructure is still insufficient. Herein, we present a tunable [CoO]6 octahedron microstructure in LiCoO2 by a chemical delithiation process. The c-strained strain of the [CoO]6 octahedron is induced to form higher valence Co ions, and the (003) crystalline layer spacing increases to allow more rapid participation of OH- in the redox reaction. Interestingly, the specific capacity of L0.75CO2 is nearly four times higher than that of LiCoO2 at 10 mA g-1. The enhanced activity originated from the asymmetric strain [CoO]6 octahedra, resulting in enhanced electronic conductivity and Co-O hybridization for accelerated redox kinetics. This finding provides new insights into the modification strategy for pseudocapacitive transition metal oxides.

Synergistic anti-infectious bronchitis virus activity of Phillygenin combined Baicalin by modulating respiratory microbiota and improving metabolic disorders.

Phillygenin (PHI) and Baicalin (Bai) are the major chemical ingredients extracted from Forsythia suspensa and Scutellaria baicalensis, respectively. The mixture of Forsythia suspensa and Scutellaria baicalensis according to the theories of Traditional Chinese Veterinary Medicine, compounded formulation can effectively exert heat-clearing and detoxifying effect, but the synergistic anti-IBV activity of PHI combined with Bai was unclear. Here, the protection of PHI combined with Bai on avian infectious bronchitis virus (IBV) M41 infection and the change of respiratory microbiota and metabolomics profiles in broilers that infected with IBV were investigated. According to the experimental findings, the combination of PHI and Bai effectively alleviated broilers' slowing-growth weight and respiratory symptoms. This was accompanied by a reduction in viral copies and histopathological changes, as well as an increase of antiviral protein (G3BP1) level in tracheas and anti-IBV antibody levels in serum. In addition, 16s RNA sequencing revealed that IBV infection significantly changed respiratory microbiota composition at different taxonomic levels and respiratory metabolism composition in broilers. Interestingly, PHI combined with Bai modulated the composition of respiratory microfloras, especially the abundance of Firmicutes and Lactobacillaceae were upregulated, as well as the abundance of Proteobacteria was downregulated. The metabolomics results indicated that PHI combined with Bai involved in glucose, lipids, amino acids and nucleotide metabolism during IBV infection. In summary, PHI combined with Bai exhibited a synergistic effect on preventing infectious bronchitis (IB), with the protection being closely associated with the composition of respiratory microbiota and metabolites. Therefore, adding the mixture of PHI and Bai to the chicken drinking water is recommended to prevent and control IB in clinical.

Cordyceps militaris Solid Medium Extract Alleviates Lipoteichoic Acid-Induced MH-S Inflammation by Inhibiting TLR2/NF-κB/NLRP3 Pathways.

The aim of this study was to investigate the inhibitory effects of Cordyceps militaris solid medium extract (CME) and cordycepin (COR) on LTA-induced inflammation in MH-S cells and their mechanisms of action. In this study, the establishment of an LTA-induced MH-S inflammation model was determined, the CCK-8 method was used to determine the safe concentration range for a drug for COR and CME, the optimal concentration of COR and CME to exert anti-inflammatory effects was further selected, and the expression of inflammatory factors of TNF-α, IL-1ß, IL-18, and IL-6 was detected using ELISA. The relative expression of TNF-α, IL-1ß, IL-18, IL-6, IL-10, TLR2 and MyD88 mRNA was detected using RT-PCR, and the IL-1ß, IL-18, TLR2, MyD88, NF-κB p-p65, NLRP3, pro-caspase-1, Caspase-1 and ASC protein expression in the cells were detected using Western blot; immunofluorescence assay detected the expression of Caspase-1 in MH-S cells. The results revealed that both CME and COR inhibited the levels of IL-1ß, IL-18, IL-6, and TNF-α in the supernatants of LTA-induced MH-S cells and the mRNA expression levels of IL-1ß, IL-18, IL-6, TNF-α, TLR2 and MyD88, down-regulated the LTA-induced IL-1ß, IL-18, TLR2 in MH-S cells, MyD88, NF-κB p-p65/p65, NLRP3, ASC, pro-caspase-1, and caspase-1 protein expression levels, and inhibited LTA-induced caspase-1 activation in MH-S cells. In conclusion, CME can play a therapeutic role in LTA-induced inflammation in MH-S cells via TLR2/NF-κB/NLRP3, and may serve as a potential drug for bacterial pneumonia caused by Gram-positive bacteria.

Integrative Transcriptomics and Proteomics Analysis Reveals Immune Response Process in Bovine Viral Diarrhea Virus-1-Infected Peripheral Blood Mononuclear Cells.

Bovine viral diarrhea virus (BVDV) causes bovine viral diarrhea-mucosal disease, inflicting substantial economic losses upon the global cattle industry. Peripheral blood mononuclear cells (PBMCs) are the central hub for immune responses during host-virus infection and have been recognized as crucial targets for BVDV infection. In order to elucidate the dynamics of host-BVDV-1 interaction, this study harnessed RNA-seq and iTRAQ methods to acquire an extensive dataset of transcriptomics and proteomics data from samples of BVDV-1-infected PBMCs at the 12-h post-infection mark. When compared to mock-infected PBMCs, we identified 344 differentially expressed genes (DEGs: a total of 234 genes with downregulated expression and 110 genes with upregulated expression) and 446 differentially expressed proteins (DEPs: a total of 224 proteins with downregulated expression and 222 proteins with upregulated expression). Selected DEGs and DEPs were validated through quantitative reverse transcriptase-polymerase chain reaction and parallel reaction monitoring. Gene ontology annotation and KEGG enrichment analysis underscored the significant enrichment of DEGs and DEPs in various immunity-related signaling pathways, including antigen processing and presentation, complement and coagulation cascades, cytokine-cytokine receptor interaction, and the NOD-like receptor signaling pathway, among others. Further analysis unveiled that those DEGs and DEPs with downregulated expression were predominantly associated with pathways such as complement and coagulation cascades, the interleukin-17 signaling pathway, cytokine-cytokine receptor interaction, the PI3K-Akt signaling pathway, the tumor necrosis factor signaling pathway, and the NOD-like receptor signaling pathway. Conversely, upregulated DEGs and DEPs were chiefly linked to metabolic pathways, oxidative phosphorylation, complement and coagulation cascades, and the RIG-I-like receptor signaling pathway. These altered genes and proteins shed light on the intense host-virus conflict within the immune realm. Our transcriptomics and proteomics data constitute a significant foundation for delving further into the interaction mechanism between BVDV and its host.

Polymer Chainmail: Steric Hindrance and Charge Compensation of Anion-Doped PEDOT to Boost Stress Deformation of Compressible Supercapacitor.

Conducting polymers with high theoretical capacitance and deformability are among the optimal candidates for compressible supercapacitor electrode materials. However, achieving both mechanical and electrochemical stabilities in a single electrode remains a great challenge. To address this issue, the "Polymer Chainmail" is proposed with reversible deformation capability and enhances stability because of the steric hindrance and charge compensation effect of doped anions. As a proof of concept, four common anions are selected as dopants for Poly(3,4-ethylenedioxythiophene) (PEDOT), and their effects on the adsorption and diffusion of H+ on PEDOT are verified using density functional theory calculations. Owing to the film formation effect, the PF 6 - ${{\rm{PF}}_6^- }$ doped PEDOT/nitrogen-doped carbon foam exhibits good mechanical properties. Furthermore, the composite demonstrates excellent rate performance and stability due to suitable anion doping. This finding provides new insights into the preparation of electrochemically stable conductive polymer-based compressible electrode materials.

Dietary supplementation with different alternative to in-feed antibiotic improves growth performance of broilers during specific phases.

The effects of substituting Bacillus subtilis, Astragalus membranaceus, and enzymes for aureomycin to improve the growth performance of broilers during specific phases were studied to develop alternatives to in-feed antibiotics and decrease drug residues in meat food and antibiotic resistance. Six hundred one-day-old broilers were randomly assigned to 5 groups. Broilers in the control group were supplied with basal diets (CT), and those in the remaining 4 groups were supplied with feed containing aureomycin premix (AU), B. subtilis powder (BS), A. membranaceus root powder (AM), and enzyme compound powder (EN), respectively. Compared to the control group, broilers in the other groups exhibited better growth performance during different phases. Microbial analysis of cecal contents suggested that treatment with BS or EN significantly increased the abundance of Lactobacillus or Bifidobacteria but inhibited Escherichia coli or Clostridium welchii; however, these bacteria were suppressed by AU treatment except C. welchii. The digestibility of the feed in vitro was significantly enhanced by adding BS or EN to the feed, consistent with findings for growth performance. In conclusion, dietary supplementation with 3 additives could improve the growth performance of broilers during specific phases. Future studies should focus on designing suitable schedules to partially replace in-feed antibiotics.

Genome Analysis and Safety Assessment of Achromobacter marplatensis Strain YKS2 Strain Isolated from the Rumen of Yaks in China.

Achromobacter marplatensis strain YKS2 isolated from the yak rumen has the feature of producing cellulose. This study aims to analyze the genome and safety of strain YKS2 in vivo, considering its future research and application prospects. The genome of strain YKS2 was sequenced and used for genomic in silico studies. The administration of strain YKS2 in three doses was carried out on mice for 3 days of oral and 7 days of clinical observation tests. The BW, FI, organ indices, gut microbiota, and histological appearances of organs and intestines, along with hematological parameters and serum biochemistry, were measured in mice. The chromosome size of strain YKS2 was 6,588,568 bp, with a GC content of 65.27%. The 6058 coding sequences of strain YKS2 without plasmid were predicted and annotated and have multiple functions. The mice in all groups were alive, with good mental states and functional activities. Compared with the control group, there was no significant difference in the three dose groups on BW, FI, hematological parameters (WBC, LYM, etc.), and serum biochemistry (ALB, ALT, etc.). No abnormalities were observed in the main visceral organs, intestinal tissue, and V/C value in groups. However, the IEL number of duodenum and gut microbiota diversity (Shannon's index) in the high-dose group was significantly higher than in the control group (p < 0.05). Besides, the low dose of strain YKS2 also significantly affected the bacterial abundance of Firmicutes, Actinobacteria, and desulphurizing Bacteroidetes at the phylum level. There was no significant effect at genus levels in groups. In conclusion, the study revealed the genome and potential functional genes of strain YKS2, which is beneficial to understanding the features of the A. marplatensis strain and proved strain YKS2 to be without acute toxicity to mice. However, a long-term feeding toxicity experiment in vivo should be performed to further ensure its potential application value strain in the animal industry.

Asiatic acid and andrographolide reduce hippocampal injury through suppressing neuroinflammation caused by Salmonella typhimurium infection.

Damage caused by Salmonella is not only limited to the gastrointestinal tract, but also occurs in the central nervous system (CNS). The aim of this study was to explore the protective effects of asiatic acid (AA) and andrographolide (AD) on the CNS through simulating common infection in mice by oral administration of Salmonella typhimurium (S. typhimurium). The results showed that the neurons in the hippocampus of mice were damaged after S. typhimurium invaded CNS in mice, and the inflammation was increased, which was manifested by the increased expression of inflammatory factors interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, interferon (IFN)-γ and IL-12b and the activation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes. The damage and inflammatory response of mouse hippocampal neurons were effectively reduced by AA or AD pretreatment. Furthermore, we observed the significant activation of microglia after S. typhimurium infection. AA and AD attenuated S. typhimurium -induced hippocampal injury by reducing the inflammatory response on microglia. The findings suggest that the AA and AD protect CNS from injury caused by S. typhimurium infection through inhibiting over expression of multiple neuroinflammatory mediators and NLRP3 inflammasome in mice.

Molecular Characteristics, Functional Definitions, and Regulatory Mechanisms for Cross-Presentation Mediated by the Major Histocompatibility Complex: A Comprehensive Review.

The major histocompatibility complexes of vertebrates play a key role in the immune response. Antigen-presenting cells are loaded on MHC I molecules, which mainly present endogenous antigens; when MHC I presents exogenous antigens, this is called cross-presentation. The discovery of cross-presentation provides an important theoretical basis for the study of exogenous antigens. Cross-presentation is a complex process in which MHC I molecules present antigens to the cell surface to activate CD8+ T lymphocytes. The process of cross-representation includes many components, and this article briefly outlines the origins and development of MHC molecules, gene structures, functions, and their classical presentation pathways. The cross-presentation pathways of MHC I molecules, the cell lines that support cross-presentation, and the mechanisms of MHC I molecular transporting are all reviewed. After more than 40 years of research, the specific mechanism of cross-presentation is still unclear. In this paper, we summarize cross-presentation and anticipate the research and development prospects for cross-presentation.

High mobility group box-1 regulates expression of EGFR, VEGF, StAR and TIMP1/2 in bovine granulosa cells through a mechanism involving TLR2/NF-κB.

Innate immunity is involved in ovarian activity through aseptic inflammation and tissue repair. High-mobility group box-1 (HMGB1) is related to placental inflammation and a driver of inflammation throughout pregnancy. The aim of this study was to investigate the interaction of HMGB1 with TLR2 in bovine ovarian granulosa cells, and the effects of HMGB1 on bovine ovarian granulosa cells in vitro. The viability of granulosa cells were not affected by HMGB1 with the concentration less than 5 µg/mL. The mRNA levels of TLR2, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), the steroidogenic acute regulatory protein (StAR), tissue inhibitors of matrix (TIMP1/2) of ovarian granulosa cells were upregulated by HMGB1(P < 0.05). The protein levels of TLR2, TLR1 and phosphorylation-NF-κB (p-NF-κB) p65 in ovarian granulosa cells increased in 5 µg/mL HMGB1 group (P < 0.05), and TLR2 decreased in siRNA-2 group (P < 0.05). IL-6 of ovarian granulosa cells was increased by 1 µg/mL and 5 µg/mL HMGB1 (P < 0.05). These results implicate that HMGB1 has interaction with TLR2, TLR1 and p-NF-κB p65 in ovarian granulosa cells, which lead to nuclear translocation of NF-κB p65 and the secretion of interleukin-6 (IL-6). HMGB1 regulates the expression of EGFR, VEGF, StAR, TIMP1/2 and the secretion of IL-6 in ovarian granulosa cells of dairy cows through activating the TLR2/NF-κB signaling pathway, which may be interfere with ovarian physiological activity.

Uridine affects amino acid metabolism in sow-piglets model and increases viability of pTr2 cells.

Background: As an important nucleoside precursor in salvage synthesis pathway of uridine monophosphate, uridine (UR) is the most abundant nucleotide in sow milk. This study aimed to investigate the effects of maternal UR supplementation during second trimester of gestation on reproductive performance and amino acid metabolism of Sows. Results: Results showed that compared to CON group, the average number of stillborn piglets per litter was significantly reduced (P < 0.05) with higher average piglet weight at birth in UR group (P = 0.083). Besides, dietary UR supplementation significantly increased TP in sow serum, BUN content in cord serum, and TP and ALB in newborn piglet serum (P < 0.05); but decreased AST level in sow serum and BUN level in piglet serum (P < 0.05). Importantly, free amino acids profile in sow serum newborn piglet serum and colostrum was changed by maternal UR supplementation during day 60 of pregnancy, as well as the expression of amino acids transporter (P < 0.05). In addition, from 100 to 2,000 µM UR can increased the viability of pTr2 cells. The UR exhibited higher distribution of G1/M phase of cell cycle at 400 µM compared with 0 µM, and reduced S-phases of cell cycle compared with 0 and 100µM (P < 0.05). Conclusion: Supplementation of uridine during day 60 of pregnancy can improve reproductive performance, regulate amino acid metabolism of sows and their offspring, and increase the viability of pTr2 cells.

Differential proteomic of plasma provides a new perspective on scientific diagnosis and drug screening for dampness heat diarrhea in calves.

Dampness heat diarrhea (DHD) is one of the most common syndromes of calf diarrhea. Its complex etiology and lack of objective diagnostic criteria bring great challenges to the diagnosis and treatment of this disease. This study aims to screen some prospective diagnostic biomarkers or therapeutic targets for calves with DHD by investigating the differential protein profiles of plasma between DHD calves and clinically healthy calves by mass spectrometry-based proteomic. A total of 120 DHD calves and 90 clinically healthy calves were divided into two groups randomly, 30 DHD calves and 30 clinically healthy calves in the test group, and 90 DHD calves and 60 clinically healthy calves in the validation group. In the test group, a total of 52 proteins were differentially expressed between calves with DHD and clinically healthy calves, 13 proteins were significantly increased and 39 proteins were significantly decreased. The differentially expressed proteins were associated with the intestinal immune network of IgA production, caffeine metabolism, purine metabolism, and PI3K signaling pathway. In the validation group, 13 proteins were selected from 52 differential expression proteins for parallel reaction monitoring validation to verify their associations with DHD calves. The targeted proteomic results showed that fibronectin precursor (FN1) and apolipoprotein C-IV precursor (APOC4) were significantly associated with DHD in calves, and they were downregulated in sick calves. In conclusion, the differential expression of plasma proteins was associated with DHD pathogenesis in calves, and the FN1 and APOC4 might be the potential clinical biomarkers for diagnosis of DHD in calves, and the intestinal immune network of IgA production, caffeine metabolism, purine metabolism, and PI3K signaling pathway are the candidate targets to treat DHD in calves. Our finding provides a reference for further investigating the pathogenesis, developing techniques of diagnosis, and screening treatment drugs for DHD in calves.

Asiatic Acid Attenuates Inflammation Induced by Salmonella via Upregulating LncRNA TVX1 in Microglia.

Salmonella typhimurium (S.T) induces damage to the central nervous system; however, the role of Asiatic acid (AA) in this is still unknown. Microglia play a role as macrophages to recognize the invaded pathogenic microbes in the brain. The aim of this study was to investigate the protective effect and mechanism of AA on the central nervous system through an in vitro model of S.T infection in microglia. We pre-treated microglia with AA before S.T infection and explored the anti-infection mechanism of AA by sequencing, quantitative reverse transcription PCR (RT-qPCR), and Western blotting. Long non-coding RNA (lncRNA) sequencing demonstrated that inflammation is a major factor in S.T infection of microglia. RT-qPCR data demonstrated that AA inhibited S.T-induced increases in the mRNA levels of the pro-inflammatory factors interleukin (IL)-1ß, IL-6, and IL-18. Western blotting demonstrated that AA inhibited S.T-induced activation of the nuclear factor (NF)-κB pathway and activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome. Expression of the lncRNA TVX1 in microglia was decreased by S.T infection and increased by pretreatment with AA. Inhibition of TVX1 expression reversed the anti-inflammatory effect of AA, and overexpression of TVX1 in microglia suppressed S.T-induced inflammation. In conclusion, AA attenuated S.T-induced microglial inflammation by upregulating the expression of the lncRNA TVX1.

Antiviral activity and underlying mechanisms of baicalin against avian infectious bronchitis virus in vitro.

Baicalin, a flavonoid compound extracted from the dry root of Scutellaria baicalensis Georgi, has been shown to have anti-inflammation, anti-viral, anti-bacterial, and immunomodulatory activity. However, the effect of baicalin against avian infectious bronchitis virus (IBV) remains unknown. The purpose of this study was to investigate the anti-IBV activity and underlying mechanism of baicalin in vitro. The results showed that baicalin has a direct virucidal effect but no prophylactic effect on IBV infection. The mRNA and protein of IBV N were decreased significantly when IBV-infected cells were treated with baicalin during the multiple stages of the virus replication cycle, including viral adsorption, invasion, internalization, and release. Stress granule (SG) formation resulted from the increase of G3BP1 and the phosphorylation of the PKR/eIF2α due to the treatment of IBV-infected cells with baicalin. The inhibitory activity of baicalin on IBV replication was increased when G3BP1 expression was inhibited, and the down-regulation of G3BP1 expression occurred when the expression of PKR and eIF2α was inhibited. These findings revealed that baicalin activates phosphorylation of the PKR/eIF2α pathway and induces SG formation by targeting G3BP1, initiating the antiviral response to suppress IBV replication in Vero cells. The results suggest that baicalin is a promising candidate drug to treat or prevent IBV infection.RESEARCH HIGHLIGHTS Baicalin inhibits IBV replication by reducing IBV N protein and mRNA.Baicalin disturbs multiple stages of the IBV life cycle.Baicalin activates PKR/eIF2α pathway and induces stress granule formation to exert anti-IBV response.

Prevalence characteristic of BVDV in some large scale dairy farms in Western China.

The aim of this study was to analyze the prevalence characteristic of Bovine viral diarrhea virus (BVDV) in some large scale dairy farms in Western China. BVDV was detected in 30 samples of bulk tank milk (BTM) collected from 30 large dairy farms in 7 provinces of western China, 93.33% (28/30) of the farms were infected with BVDV, and S/P ratio was over 0.3 in 28 positive farms. The individual status was further estimated in the dairy farm (No. 10) with the highest positive rate (S/P ratio = 1.37) and the dairy farm (No. 17) with the lowest positive rate (S/P ratio = 0.39). Two hundred cows were, respectively, selected from calf, young cows and lactating cows in farm No. 10 and farm No. 17 and the serum sample of each enrolled cow was collected. The individual positive rate of serum antibody (Ab) was 87.17% (523/600) in farm No. 10 and 31.33% (188/600) in farm No. 17. The individual positive ratio of serum antibody in calves, young cows and lactating cows were 41.75 % (167/400), 58.75% (235/400) and 77.25% (309/400), respectively. BTM Ab of farm No. 10 has an S/P ratio more than 1.0, which indicated there were emergent or persistent infection (PI) cases, and further test showed that PI cases were 0.51% in farm No. 10. Pathogens were positive in 42.34% (163/385) of nasal mucus samples collected from cows with respiratory symptom, and BVDV cases were 57 in 163 positive samples. Three strains of NCP BVDV-1, one strain of CP BVDV-1, one strain of NCP BVDV-2 and one strain of CP BVDV-2 were successfully isolated. Phylogenetic analysis revealed that the subtypes of BVDV currently prevalent in western China were BVDV-1a, BVDV-1m, BVDV-1q and BVDV-2. The findings suggested that the BVDV infection is serious in some Large Scale Dairy Farms in Western China.