To evaluate the effects on biochemicals, antioxidants, immune responses and disease resistance of the snakehead fish, following exposure to deltamethrin at 0.061, 0.121, 0.242, 0.485 and 0.970 μg/L. ...After 28 d, the biochemical, the levels of antioxidant enzymes and immune enzymes in liver, spleen, kidney and intestine were negatively related to the concentrations of deltamethrin exposure. Likewise, the survival rates of the fish after 7 d challenge with Aeromonas veronii were negatively related. The levels of IL-1β, IL-8, TNF-α, Hsp70 and malondialdehyde in liver, spleen, kidney and intestine were positively connected to the concentrations of deltamethrin exposure. Results demonstrated that environmentally relevant concentrations (0.121, 0.242, 0.485 and 0.970 μg/L) inhibited the biochemicals, antioxidants and immune responses and disease resistance of snakehead fish.
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•Deltamethrin exposure reduce the hepatopancreas function in C. argus.•Deltamethrin exposure caused tremendous oxidative damage of C. argus.•Deltamethrin exposure significantly suppressed the immune responses of C. argus.•Deltamethrin exposure caused a decrease in resistance to pathogen infection.
Lactic acid bacteria (LAB) has been documented to promoting growth, enhancing immunity and disease resistance. In this study, we aimed to evaluate the single or conjoint effects of Lactococcus lactis ...L19 (Genbank: MT102745.1) and Enterococcus faecalis W24 (Genbank: MT102746.1) isolated from the intestine of Channa argus (C. argus) on growth performance, immune response and disease resistance of C. argus. A total of 720 apparently healthy C. argus (9.50 ± 0.03 g) were randomly divided into four equal groups. Fish were fed with a basal diet (CK) supplemented with L. lactis (L19), E. faecalis (W24), and L. lactis L19 + E. faecalis W24 (L + W) at 1.0 × 108 cfu/g basal diet for 56 days. After feeding, the final body weight (FBW), weight gain (WG), feed efficiency ratio (FER), specific growth rate (SGR) and protein efficiency ratio (PER) had significantly increased (p < 0.05), especially with L19. The results indicated that single or conjoint administration of LAB as potential probiotics can induce high levels of IgM, ACP, AKP, LZM, C3 and C4 activity in serum, which may effectively induce humoral immunity, and L19 induce even higher levels. Meanwhile, when compared to CK group, the results of qPCR showed that LAB administration significantly up-regulated (p < 0.05) the expression of IL-1β, IL-6, IL-10, TNF-α, IFN-γ, HSP70, HSP90, TGF-β in the spleen, head kidney, gill, liver and intestine of C. argus. After challenge with Aeromonas veronii, the survival rates in all LAB-fed groups were significantly higher (p < 0.05) than that of the CK group, and the L19 group showed the highest (63.3%) disease resistance. Our data indicated that L. lactis L19 and E. faecalis W24, as a feed additive at 1.0 × 108 cfu/g feed, could promote growth performance, enhance immune response and disease resistance of C. argus, with greatest effects in fish fed L. lactis L19 for 56 days. Hence, these LAB additives could be used as promising probiotics for C. argus. L19 was more effective than W24 or the mixture of the two for promoting growth performance, enhancing immune response and disease resistance of C. argus.
•Diet supplemented with single or conjoint Lactococcus lactis L19 and Enterococcus faecalis W24 enhanced the growth, humoral immunity, regulated immune-related genes expression and disease resistance against Aeromonas veroniiof Channa argus.•Lactococcuslactis L19 was more effective protection than Enterococcus faecalis W24 or the mixture of the two for promoting growth performance, enhancing immune response and disease resistance of Channa argus.
Mastitis in dairy cows affects milk quality and thereby constrains the development of the dairy industry. A clear understanding of the pathogenesis of mastitis can help its treatment. Mastitis is ...caused by the invasion of pathogenic bacteria into the mammary gland through the mammary ducts. However, recent studies suggested that an endogenous entero-mammary pathway in dairy cattle might also be playing an important role in regulating mastitis. Also, probiotic intervention regulating host gut microbes has become an interesting tool to control mastitis. This review discusses the association of gastrointestinal microbes with mastitis and the mechanism of action of probiotics in dairy cows to provide new ideas for the management of mastitis in large-scale dairy farms.
•Mastitis in dairy cows affects milk quality and thereby constrains the development of the dairy industry. A clear understanding of the pathogenesis of mastitis can help its treatment.•GI microorganisms regulate the occurrence of mastitis in dairy cows.•Probiotics can be involved in mastitis control in dairy cows by rebalancing the gastrointestinal microorganisms.
Miscarriage poses a significant threat to pregnant women globally. Recurrent miscarriages or potential poor embryonic development indicated by early drops in serum human chorionic gonadotrophin (hCG) ...are even more catastrophic for pregnant women. However, these patients receive either individualized medical intervention supported by limited evidence or no treatment at all. In this study, we report ten patients who shared at least one episode of an early decline of hCG in the first trimester and were treated with compassionate use of tumor necrosis factor-alpha inhibitor (TNFi). They were then followed up regularly with caution. Their hCG trajectory all resumed a normal pattern within one week and the obstetric outcomes were promising. No adverse fetal, neonatal, or maternal health issues have been observed. This case series supports current safety evidence of TNFi and provides new insight into its use in pregnancy when the embryo is in danger. Further well-designed clinical trials should be carried out to consolidate the evidence.
Site selection is an important and necessary issue for waste management in fast-growing regions. Because of the complexity of waste management systems, the selection of the appropriate solid waste ...landfill site requires consideration of multiple alternative solutions and evaluation criteria. Based on actual conditions of the study area, we considered economic factors, calculated criteria weights using the analytical hierarchy process (AHP), and built a hierarchy model for solving the solid waste landfill site-selection problem in Beijing, China. A geographic information system (GIS) was used to manipulate and present spatial data. All maps are graded from 1 (lowest suitability) to 5 (highest suitability) using spatial information technologies. The candidate sites were determined by aggregation based on the criteria weights. The candidate sites are divided by ‘best’, ‘good’ and ‘unsuitable’ landfill areas. Best landfill areas represent optimal sites; good landfill areas can be used as back-up candidate sites. Our work offers a siting methodology and provides essential support for decision-makers in the assessment of waste management problems in Beijing and other rapidly developing cities in developing countries.
Immune checkpoint inhibitors have some efficacy in the treatment of hepatocellular carcinoma (HCC). Programmed cell death 1 ligand 1 (PD-L1), expressed on some cancer cells, binds to the receptor ...programmed cell death 1 (PDCD1, also called PD1) on T cells to prevent their proliferation and reduce the antigen-tumor immune response. Immune cells that infiltrate some types of HCCs secrete interferon gamma (IFNG). Some HCC cells express myocyte enhancer factor 2D (MEF2D), which has been associated with shorter survival times of patients. We studied whether HCC cell expression of MEF2D regulates expression of PD-L1 in response to IFNG.
We analyzed immune cells from 20 fresh HCC tissues by flow cytometry. We analyzed 225 fixed HCC tissues (from 2 cohorts) from patients in China by immunohistochemistry and obtained survival data. We created mice with liver-specific knockout of MEF2D (MEF2DLPC-KO mice). We knocked out or knocked down MEF2D, E1A binding protein p300 (p300), or sirtuin 7 (SIRT7) in SMMC-7721, Huh7, H22, and Hepa1-6 HCC cell lines, some incubated with IFNG. We analyzed liver tissues from mice and cell lines by RNA sequencing, immunoblot, dual luciferase reporter, and chromatin precipitation assays. MEF2D protein acetylation and proteins that interact with MEF2D were identified by coimmunoprecipitation and pull-down assays. H22 cells, with MEF2D knockout or without (controls), were transplanted into BALB/c mice, and some mice were given antibodies to deplete T cells. Mice bearing orthotopic tumors grown from HCC cells, with or without knockout of SIRT7, were given injections of an antibody against PD1. Growth of tumors was measured, and tumors were analyzed by immunohistochemistry and flow cytometry.
In human HCC specimens, we found an inverse correlation between level of MEF2D and numbers of CD4+ and CD8+ T cells; level of MEF2D correlated with percentages of PD1-positive or TIM3-positive CD8+ T cells. Knockout of MEF2D from H22 cells reduced their growth as allograft tumors in immune-competent mice but not in immune-deficient mice or mice with depletion of CD8+ T cells. When MEF2D-knockout cells were injected into immune-competent mice, they formed smaller tumors that had increased infiltration and activation of T cells compared with control HCC cells. In human and mouse HCC cells, MEF2D knockdown or knockout reduced expression of PD-L1. MEF2D bound the promoter region of the CD274 gene (encodes PD-L1) and activated its transcription. Overexpression of p300 in HCC cells, or knockout of SIRT7, promoted acetylation of MEF2D and increased its binding, along with acetylated histones, to the promoter region of CD274. Exposure of HCC cells to IFNG induced expression of p300 and its binding MEF2D, which reduced the interaction between MEF2D and SIRT7. MEF2D-induced expression of PD-L1 upon IFNG exposure was independent of interferon-regulatory factors 1 or 9. In HCC cells not exposed to IFNG, SIRT7 formed a complex with MEF2D that attenuated expression of PD-L1. Knockout of SIRT7 reduced proliferation of HCC cells and growth of tumors in immune-deficient mice. Compared with allograft tumors grown from control HCC cells, in immune-competent mice, tumors grown from SIRT7-knockout HCC cells expressed higher levels of PD-L1 and had reduced infiltration and activation of T cells. In immune-competent mice given antibodies to PD1, allograft tumors grew more slowly from SIRT7-knockout HCC cells than from control HCC cells.
Expression of MEF2D by HCC cells increases their expression of PD-L1, which prevents CD8+ T-cell–mediated antitumor immunity. When HCC cells are exposed to IFNG, p300 acetylates MEF2D, causing it to bind the CD274 gene promoter and up-regulate PD-L1 expression. In addition to promoting HCC cell proliferation, SIRT7 reduced acetylation of MEF2D and expression of PD-L1 in HCC cells not exposed to IFNG. Strategies to manipulate this pathway might increase the efficacy of immune therapies for HCC.
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The inflammatory response to chronic injury affects tissue regeneration and has become an important factor influencing the prognosis of patients. In previous stem cell treatments, it was revealed ...that stem cells not only have the ability for direct differentiation or regeneration in chronic tissue damage but also have a regulatory effect on the immune microenvironment. Stem cells can regulate the immune microenvironment during tissue repair and provide a good “soil” for tissue regeneration. In the current study, the regulation of immune cells by mesenchymal stem cells (MSCs) in the local tissue microenvironment and the tissue damage repair mechanisms are revealed. The application of the concepts of “seed” and “soil” has opened up new research avenues for regenerative medicine. Tissue engineering (TE) technology has been used in multiple tissues and organs using its biomimetic and cellular cell abilities, and scaffolds are now seen as an important part of building seed cell microenvironments. The effect of tissue engineering techniques on stem cell immune regulation is related to the shape and structure of the scaffold, the preinflammatory microenvironment constructed by the implanted scaffold, and the material selection of the scaffold. In the application of scaffold, stem cell technology has important applications in cartilage, bone, heart, and liver and other research fields. In this review, we separately explore the mechanism of MSCs in different tissue and organs through immunoregulation for tissue regeneration and MSC combined with 3D scaffolds to promote MSC immunoregulation to repair damaged tissues.
H7N9 avian influenza viruses have caused severe harm to the global aquaculture industry and human health. For further understanding of the characteristics of prevalence and hemagglutinin evolution of ...H7N9 avian influenza viruses, we generated the global epidemic map of H7N9 viruses from 2013 to 2022, constructed a phylogenetic tree, predicted the glycosylation sites and compared the selection pressure of the hemagglutinin. The results showed that although H7N9 avian influenza appeared sporadically in other regions worldwide, China had concentrated outbreaks from 2013 to 2017. The hemagglutinin genes were classified into six distinct lineages: A, B, C, D, E and F. After 2019, H7N9 viruses from the lineages B, E and F persisted, with the lineage B being the dominant. The hemagglutinin of highly pathogenic viruses in the B lineage has an additional predicted glycosylation site, which may account for their persistent pandemic, and is under more positive selection pressure. The most recent ancestor of the H7N9 avian influenza viruses originated in September 1991. The continuous evolution of hemagglutinin has led to an increase in virus pathogenicity in both poultry and humans, and sustained human-to-human transmission. This study provides a theoretical basis for better prediction and control of H7N9 avian influenza.
Dual-permeability flow and stress sensitivity effect are two fundamental issues that have been widely investigated in transient pressure analysis for horizontal wells. However, few attempts have been ...made to simulate the combined effects of dual-permeability flow and stress-dependent fracture permeability on the pressure transient dynamics of a horizontal well in a naturally fractured gas reservoir. In this approach, an analytical model is proposed to integrate the complexities of pressure-dependent PVT properties, dual-permeability flow behavior, and stress-dependent fracture permeability characteristics. The nonlinearity of the mathematical model is weakened by using Pedrosa’s transform formulation. Then, the Laplace integral transformation and separation of variables are applied to solve the model. Based on the solution of the mathematical model, a series of new-type curves are drawn to make a precise observation of different flow regimes. The main differences between the proposed model and the traditional models are discussed, and the effects of the permeability modulus of fractures, storability ratio, interporosity flow factor, and skin factor on transient pressure response are also examined. The results show that there are obvious differences in transient pressure dynamic curves between the proposed model and traditional models. The stress sensitivity effect plays a significant role in the intermediate flow period and the late-time pseudoradial flow period. The dual-permeability flow behavior mainly affects the early transient and interporosity flow stages. The proposed model can accurately simulate the transient pressure behaviors of a horizontal well in a naturally fractured gas reservoir with a dual-permeability flow and stress sensitivity effect. The novel model can be used to interpret pressure signals with accurate matching results and more reasonable interpreted parameters.
(
) is closely associated with the occurrence of puerperal metritis in dairy cows.
carries some the virulence and multi-drug resistant genes, which pose a serious threat to the health of postpartum ...cows. In this study,
was isolated and identified from the uterine contents of postpartum cows with puerperal metritis in the Ningxia region of China, and its phylogenetic subgroups were determined. Meanwhile, virulence and drug resistance genes carried by
and drug sensitivity were detected, and the characteristics of virulence and drug resistance genes distribution in
phylogroups were further analyzed. The results showed that the isolation rate of
in puerperal metritis samples was 95.2%.
was mainly divided into phylogroups B2 and D, followed by groups A and B1, and was more connected to O157:H7, O169:H4, and ECC-1470 type strains. The virulence genes were mainly dominated by
(100%),
(100%),
(97%),
(96%),
(95%),
(93.9%), and
(93%), and the resistance genes were dominated by
(99%),
(71.7%),
(66.7%), and
(53.5%). Additionally, it was observed that the virulence and resistance gene phenotypes could be divided into two subgroups, with subgroup B2 and D having the highest distributions. Drug sensitivity tests also revealed that the
was most sensitive to the fluoroquinolones enrofloxacin, followed by macrolides, aminoglycosides, tetracyclines, β-lactams, peptides and sulfonamides, and least sensitive to lincosamides. These results imply that pathogenic
, which induces puerperal metritis of dairy cows in the Ningxia region of China, primarily belongs to the group B2 and D, contains multiple virulence and drug resistance genes, Moreover,
has evolved resistance to several drugs including penicillin, lincomycin, cotrimoxazole, and streptomycin. It will offer specific guidelines reference for the prevention and treatment of puerperal metritis in dairy cows with
infections in the Ningxia region of China.
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