Development of a colloidal gold immunochromatographic assay strip using monoclonal antibody for rapid detection of porcine deltacoronavirus

Porcine deltacoronavirus (PDCoV) cause diarrhea and dehydration in newborn piglets and has the potential for cross-species transmission. Rapid and early diagnosis is important for preventing and controlling infectious disease. In this study, two monoclonal antibodies (mAbs) were generated, which could specifically recognize recombinant PDCoV nucleocapsid (rPDCoV-N) protein. A colloidal gold immunochromatographic assay (GICA) strip using these mAbs was developed to detect PDCoV antigens within 15 min. Results showed that the detection limit of the GICA strip developed in this study was 103 TCID50/ml for the suspension of virus-infected cell culture and 0.125 μg/ml for rPDCoV-N protein, respectively. Besides, the GICA strip showed high specificity with no cross-reactivity with other porcine pathogenic viruses. Three hundred and twenty-five fecal samples were detected for PDCoV using the GICA strip and reverse transcription-quantitative real-time PCR (RT-qPCR). The coincidence rate of the GICA strip and RT-qPCR was 96.9%. The GICA strip had a diagnostic sensitivity of 88.9% and diagnostic specificity of 98.5%. The specific and efficient detection by the strip provides a convenient, rapid, easy to use and valuable diagnostic tool for PDCoV under laboratory and field conditions

Biomimetic Metal-Organic Nanoparticles Prepared with a 3D-Printed Microfluidic Device as a Novel Formulation for Disulfiram-Based Therapy Against Breast Cancer

Disulfiram (DSF) is currently tested in several clinical trials for cancer treatment in combination with cop-per (Cu) ions. Usually, DSF and Cu are administered in two separate formulations. In the body, DSF andCu ions form diethyldithiocarbamate copper complex [Cu(DDC)2] which has potent antitumor activities.However, the “two formulation” approach often achieved low Cu(DDC)2 concentration at tumor regions and resulted in compromised anticancer efficacy. Therefore, preformed Cu(DDC)2 complex administered in a single formulation will have better anticancer efficacy. However, the poor aqueous solubility of Cu(DDC)2 is a significant challenge for its clinical use. In this work, a biomimetic nanoparticle formulation of Cu(DDC)2 was produced with a novel SMILE (Stabilized Metal Ion Ligand complex) method developed in our laboratory to address the drug delivery challenges. The Metal-organic Nanoparticle (MON) is composed of Cu(DDC)2 metal-organic complex core and surface decorated bovine serum albumin (BSA). Importantly, we designed a 3D-printed microfluidic device to further improve the fabrication of BSA/Cu(DDC)2 MONs. This method could precisely control the MON preparation process and also has great potential for large scale production of Cu(DDC)2 MON formulations. We also used a computational modeling approach to simulate the MON formation process in the microfluidic device. The optimized BSA/Cu(DDC)2 MONs demonstrated good physicochemical properties. The MONs also showed potent antitumor activities in the breast cancer cell monolayers as well as the 3D-cultured tumor spheroids. The BSA/Cu(DDC)2 MONs also effectively inhibited the growth of tumors in an orthotopic 4T1 breast tumor model. This current study provided a novel method to prepare a biomimetic MON formulation for DSF/Cu cancer therapy .© 2019 Elsevier Ltd. All rights reserved

Association between methionine sulfoxide and risk of moyamoya disease

ObjectiveMethionine sulfoxide (MetO) has been identified as a risk factor for vascular diseases and was considered as an important indicator of oxidative stress. However, the effects of MetO and its association with moyamoya disease (MMD) remained unclear. Therefore, we performed this study to evaluate the association between serum MetO levels and the risk of MMD and its subtypes.MethodsWe eventually included consecutive 353 MMD patients and 88 healthy controls (HCs) with complete data from September 2020 to December 2021 in our analyzes. Serum levels of MetO were quantified using liquid chromatography-mass spectrometry (LC–MS) analysis. We evaluated the role of MetO in MMD using logistic regression models and confirmed by receiver-operating characteristic (ROC) curves and area under curve (AUC) values.ResultsWe found that the levels of MetO were significantly higher in MMD and its subtypes than in HCs (p < 0.001 for all). After adjusting for traditional risk factors, serum MetO levels were significantly associated with the risk of MMD and its subtypes (p < 0.001 for all). We further divided the MetO levels into low and high groups, and the high MetO level was significantly associated with the risk of MMD and its subtypes (p < 0.05 for all). When MetO levels were assessed as quartiles, we found that the third (Q3) and fourth (Q4) MetO quartiles had a significantly increased risk of MMD compared with the lowest quartile (Q3, OR: 2.323, 95%CI: 1.088–4.959, p = 0.029; Q4, OR: 5.559, 95%CI: 2.088–14.805, p = 0.001).ConclusionIn this study, we found that a high level of serum MetO was associated with an increased risk of MMD and its subtypes. Our study raised a novel perspective on the pathogenesis of MMD and suggested potential therapeutic targets

Chinese Cerebrovascular Neurosurgery Society and Chinese Interventional & Hybrid Operation Society, of Chinese Stroke Association Clinical Practice Guidelines for Management of Brain Arteriovenous Malformations in Eloquent Areas

Aim: The aim of this guideline is to present current and comprehensive recommendations for the management of brain arteriovenous malformations (bAVMs) located in eloquent areas.Methods: An extended literature search on MEDLINE was performed between Jan 1970 and May 2020. Eloquence-related literature was further screened and interpreted in different subcategories of this guideline. The writing group discussed narrative text and recommendations through group meetings and online video conferences. Recommendations followed the Applying Classification of Recommendations and Level of Evidence proposed by the American Heart Association/American Stroke Association. Prerelease review of the draft guideline was performed by four expert peer reviewers and by the members of Chinese Stroke Association.Results: In total, 809 out of 2,493 publications were identified to be related to eloquent structure or neurological functions of bAVMs. Three-hundred and forty-one publications were comprehensively interpreted and cited by this guideline. Evidence-based guidelines were presented for the clinical evaluation and treatment of bAVMs with eloquence involved. Topics focused on neuroanatomy of activated eloquent structure, functional neuroimaging, neurological assessment, indication, and recommendations of different therapeutic managements. Fifty-nine recommendations were summarized, including 20 in Class I, 30 in Class IIa, 9 in Class IIb, and 2 in Class III.Conclusions: The management of eloquent bAVMs remains challenging. With the evolutionary understanding of eloquent areas, the guideline highlights the assessment of eloquent bAVMs, and a strategy for decision-making in the management of eloquent bAVMs

Investigations into a putative role for the novel BRASSIKIN pseudokinases in compatible pollen-stigma interactions in Arabidopsis thaliana.

BACKGROUND: In the Brassicaceae, the early stages of compatible pollen-stigma interactions are tightly controlled with early checkpoints regulating pollen adhesion, hydration and germination, and pollen tube entry into the stigmatic surface. However, the early signalling events in the stigma which trigger these compatible interactions remain unknown. RESULTS: A set of stigma-expressed pseudokinase genes, termed BRASSIKINs (BKNs), were identified and found to be present in only core Brassicaceae genomes. In Arabidopsis thaliana Col-0, BKN1 displayed stigma-specific expression while the BKN2 gene was expressed in other tissues as well. CRISPR deletion mutations were generated for the two tandemly linked BKNs, and very mild hydration defects were observed for wild-type Col-0 pollen when placed on the bkn1/2 mutant stigmas. In further analyses, the predominant transcript for the stigma-specific BKN1 was found to have a premature stop codon in the Col-0 ecotype, but a survey of the 1001 Arabidopsis genomes uncovered three ecotypes that encoded a full-length BKN1 protein. Furthermore, phylogenetic analyses identified intact BKN1 orthologues in the closely related outcrossing Arabidopsis species, A. lyrata and A. halleri. Finally, the BKN pseudokinases were found to be plasma-membrane localized through the dual lipid modification of myristoylation and palmitoylation, and this localization would be consistent with a role in signaling complexes. CONCLUSION: In this study, we have characterized the novel Brassicaceae-specific family of BKN pseudokinase genes, and examined the function of BKN1 and BKN2 in the context of pollen-stigma interactions in A. thaliana Col-0. Additionally, premature stop codons were identified in the predicted stigma specific BKN1 gene in a number of the 1001 A. thaliana ecotype genomes, and this was in contrast to the out-crossing Arabidopsis species which carried intact copies of BKN1. Thus, understanding the function of BKN1 in other Brassicaceae species will be a key direction for future studies