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The detection of antimitochondrial antibodies (AMA) is the specific diagnostic marker for primary biliary cholangitis. Indeed, it is the most specific autoantibody in clinical autoimmunity, with a high titer directed response to the inner lipoyl domain of PDC-E2. The current international reference for AMA detection is based upon sera samples of PBC patients. In rheumatic diseases, i.e. rheumatoid arthritis, great efforts are placed at development of international standards. In this study, we report the development of a monoclonal chimeric IgG1 antibody as a reference for AMA testing. A monoclonal 4G6 antibody was constructed from a murine monoclonal antibody specific for the inner lipoyl domain (ILD) of PDC-E2, by combining the variable region with the constant region of human IgG1. The 4G6 antibody recognizes all AMA epitopes containing the ILD of PDC-E2, including the classical BPO recombinant antigen in all currently available diagnostic methods. The binding affinity of the 4G6 antibody to PDC-E2 and BPO antigen reaches KD value of 7.22 × 10−11 M and 4.55 × 10−11 M, which is sufficient to use as a quantitative reference for all AMA tests. The unlimited availability of the 4G6 antibody makes it a promising candidate for use as an AMA reference or assay calibrator for the international community.

ABSTRACT: Previous studies here have demonstrated that the rabbit sacculus rotundus-derived antimicrobial peptides (RSRP) could alter the intestinal mucosal immune responses in specific-pathogen-free (SPF) chickens, however, the protective effects of RSRP on chickens against infection remain questionable. In the present study, eighty SPF chickens were randomly divided into five groups and challenged with very virulent infectious bursal disease virus (vvIBDV) to determine the protective effects and its underlying mechanism of RSRP. Histopathology examination found that vvIBDV-infection caused severe damage in the bursa of Fabricius, especially the bursal lymphoid follicles underwent severe necrosis, depletion, hemorrhage, and edema. Unexpectedly, RSRP intervention significantly reduced the necrosis and depletion of lymphoid follicles in the vvIBDV-infected chickens. Moreover, RSRP treatment significantly decreased the expression of Bax (P < 0.01) as well as remarkably promoted the expression of Bcl-2 (P < 0.01), concomitantly alleviated the excessive apoptosis in the immune organs such as the bursa of Fabricius during vvIBDV infection. Notably, consistent with our previous reports that increased mast cell activation and degranulation in the bursa after vvIBDV infection, RSRP administration considerably reduced the mast cell density and the expression of tryptase, a marker for activated mast cells. Collectively, the present study indicates that rabbit sacculus rotundus-derived antimicrobial peptides could effectively protect the major immune organs including the bursa of Fabricius from the damage caused by vvIBDV infection, which provides the possibility and a promising perspective for the future application of antimicrobial peptides for poultry production.

Summary: Polycomb repressive complex 1 (PRC1) undergoes phase separation to form Polycomb condensates that are multi-component hubs for silencing Polycomb target genes. In this study, we demonstrate that formation and regulation of PRC1 condensates are consistent with the scaffold-client model, where the Chromobox 2 (CBX2) protein behaves as the scaffold while the other PRC1 proteins are clients. Such clients induce a re-entrant phase transition of CBX2 condensates. The composition of the multi-component PRC1 condensates (1) determines the dynamic properties of the scaffold protein; (2) selectively promotes the formation of CBX4-PRC1 condensates while dissolving condensates of CBX6-, CBX7-, and CBX8-PRC1; and (3) controls the enrichment of CBX4-, CBX7-, and CBX8-PRC1 in CBX2-PRC1 condensates and the exclusion of CBX6-PRC1 from CBX2-PRC1 condensates. Our findings uncover how multi-component PRC1 condensates are assembled via an intricate scaffold-client mechanism whereby the properties of the PRC1 condensates are sensitively regulated by its composition and stoichiometry.

Silicosis is one of the most frequent, rapidly developing, and lethal types of pneumoconiosis. However, our understanding of the underlying mechanisms of its pathogenesis and progress remains unclear. We investigated the fundamental processes of silicosis incidence and progression using a combination of lung function testing, histopathology, 16 S rRNA, untargeted metabolomics, and cytokine chips at different exposure times (4 or 8 weeks). The results show that silica exposure damages lung tissue reduces lung function, and increases with time. Cytokines with time-specific properties were found in lung lavage fluid: IFN-γ (4 weeks; P＜0.05), TNF-α, M-CSF, GM-CSF (8 weeks; P＜0.01). In addition, silica exposure for different periods interferes to varying degrees with the metabolism of lipids. The composition of the intestinal microbiota changed with increasing exposure time and there were time-specific: Allobaculum, Turicibacter、Jeotgalicoccu、Coprococcus 1 (4 weeks; P＜0.05), Ruminococcaceae NK4A214 group、Ruminiclostridium 5 (8 weeks; P＜0.05). We found strong associations between cytokines, gut microbiota changes, and metabolic disturbances at different exposure times. These results suggest that time-specific changes in crosstalk among cytokines, the gut microbiota, and metabolites may be a potential mechanism for silica-induced lung injury.

Ovarian cancer (OC) is a severe malignancy featuring a poor prognosis due to rapid metastasis and chemotherapy resistance. In this study, we extensively investigated the upstream and downstream mechanisms of miR-548e in regulating OC progression and cisplatin resistance. Our results indicated that ZFAS1 was highly expressed and promoted OC cell proliferation, migration, invasion, and cisplatin resistance by directly suppressing miR-548e expression. ZFAS1 co-localized with miR-548e in the cytosols of OC cells. miR-548e repressed CXCR4 expression, and elevated CXCR4 expression promoted OC cell proliferation, migration, invasion, and cisplatin resistance. Cisplatin resistance induced by ZFAS1 and CXCR4 overexpression in OC cells was mediated by their suppression on let-7a and elevation of BCL-XL/S expression. ZFAS1 knockdown and miR-548e and let-7a overexpression impaired cisplatin resistance and suppressed lung metastatic nodule formation in nude mice. In conclusion, ZFAS1 binds with miR-548e to enhance CXCR4 expression to promote OC cell proliferation and metastasis, which also enhances cisplatin resistance by suppressing let-7a and elevating BCL-XL/S protein expression.

Background/purpose: Clear aligners are popular orthodontic tools because of their relatively aesthetic appearance and convenience of use. Nevertheless, bodily tooth movements still present challenges. This study evaluated various configurations of attachments placed on the mandibular canine in terms of the efficiency of canine bodily movement and correction of tipping. Materials and methods: A finite element model of the mandible was constructed to investigate the effects of various attachment configurations on the overall bodily movement and undesirable tipping of a mandibular canine. Canine movements were categorized into four types, namely tipping and bodily movements in the mesial and distal directions. The size and shape of the attachments were fixed, but their placement and orientation were varied. Five and seven attachment configurations were evaluated for their influence on tipping and bodily movements, respectively. Results: Attachment configuration significantly influenced mandibular canine tipping. The mesial occlusal–distal cervical and mesial occlusal–mesial cervical configurations had notable effects on mesial tipping, and the mesial occlusal–mesial cervical configuration excelled in distal tipping by increasing strain by 33.1%. The mesial occlusal–mesial cervical attachment configuration consistently had superior efficiency in facilitating both mesial and distal bodily movements of the canine. Conclusion: The mesial occlusal–mesial cervical attachment configuration excelled in all four types of canine movement. Irrespective of the attachment configuration, canines tend to move overall with slight tipping due to skeletal resistance and their center of rotation. The attachment configuration is crucial to the success of clear aligner treatment and must be carefully considered in clinical practice.