Antibodies to SARS Coronavirus in Civets

Using three different assays, we examined 103 serum samples collected from different civet farms and a market in China in June 2003 and January 2004. While civets on farms were largely free from SARS-CoV infection, ≈80% of the animals from one animal market in Guangzhou contained significant levels of antibody to SARS-CoV, which suggests no widespread infection among civets resident on farms, and the infection of civets in the market might be associated with trading activities under the conditions of overcrowding and mixing of various animal species

Mst1-Mediated Phosphorylation of Nur77 Improves the Endometrial Receptivity in Human and Mice

Background: Successful embryo implantation requires the attachment of a blastocyst to the receptive endometrial epithelium, which was disturbed in the women with recurrent implantation failure (RIF). Endometrial β3-integrin was the most important adhesion molecule contributing to endometrial receptivity in both humans and mice. Nur77 has been proven indispensable for fertility in mice, here we explore the role of Nur77 on embryo-epithelial adhesion and potential treatment to embryo implantation failure. Methods: The expression and location of Mst1 and Nur77 in endometrium from fertile women and RIF patients were examined by IHC, qRT-PCR and Western blotting. In vitro kinase assay following with LC-MS/MS were used to identify the phosphorylation site of Nur77 activated by Mst1. The phosphorylated Nur77 was detected by phos-tag SDS-PAGE assay and specific antibody against phospho-Nur77-Thr366. The effect of embryo-epithelium interaction was determined in the BeWo spheroid or mouse embryo adhesion assay, and delayed implantation mouse model. RNA-seq was used to explore the mechanism by which Nur77 derived peptide promotes endometrial receptivity. Findings: Endometrial Mammalian sterile 20 (STE20)-like kinase 1 (Mst1) expression level was decreased in the women with RIF than that in the fertile control group, while Mst1 activation in the epithelial cells promoted trophoblast-uterine epithelium adhesion. The effect of Nur77 mediated trophoblast-uterine epithelium adhesion was facilitated by active Mst1. Mechanistically, mst1 promotes the transcription activity of Nur77 by phosphorylating Nur77 at threonine 366 (T366), and consequently increased downstream target β3-integrin expression. Furthermore, a Nur77-derived peptide containing phosphorylated T366 markedly promoted mouse embryo attachment to Ishikawa cells ([4 (2-4)] vs [3 (2-4)]) and increased the embryo implantation rate (4 vs 1.4) in a delayed implantation mouse model by regulating integrin signalling. Finally, it is observed that the endometrial phospho-Nur77 (T366) level is decreased by 80% in the women with RIF. Interpretation: In addition to uncovering a potential regulatory mechanism of Mst1/Nur77/β3-integrin signal axis involved in the regulation of embryo-epithelium interaction, our finding provides a novel marker of endometrial receptivity and a potential therapeutic agent for embryo implantation failure. Funding: National Key Research and Development Program of China (2018YFC1004400), the National Natural Science Foundation of China (82171653, 82271698, 82030040, 81971387 and 30900727), and National Institutes of Health grants (R01HL103869)

RESEARCH ON APPLYING ANALYTIC HIERARCHY PROCESS APPROACH TO TECHNOLOGY ROADMAPPING

Abstract: Technology roadmapping is a tool for technology planning which has been caused more and more attention in both academic and industrial fields. In this paper, firstly, we summarize the technical problems emerging within technology roadmapping. Then, we demonstrate a methodology based on the Analytic Hierarchy Process (AHP) to address the decision making problems in evaluating technology alternatives in technology roadmap. Finally, we present a process which is easily implemental approach to technology roadmapping.

PPARG Could Work as a Valid Therapeutic Strategy for the Treatment of Lung Squamous Cell Carcinoma

Previous studies showed that PPAR-gamma (PPARG) ligands might serve as potential therapeutic agents for nonsmall cell lung cancer (NSCLC). However, a few studies reported the specific relationship between PPARG and lung squamous cell carcinoma (LSCC). Here, we made an effort to explore the relationship between PPARG and LSCC. First, we used mega-analysis and partial mega-analysis to analyze the effects of PPARG on LSCC by using 12 independent LSCC expression datasets (285 healthy controls and 375 LSCC cases). Then, literature-based molecular pathways between PPARG and LSCC were established. After that, a gene set enrichment analysis (GSEA) was conducted to study the functionalities of PPARG and PPARG-driven triggers within the molecular pathways. Finally, another mega-analysis was constructed to test the expression changes of PPARG and its driven targets. The partial mega-analysis showed a significant downregulated expression of PPARG in LSCC (LFC=−1.08, p value=0.00073). Twelve diagnostic markers and four prognostic markers were identified within multiple PPARG-LSCC regulatory pathways. Our results suggested that the activation of PPARG expression may inhibit the development and progression of LSCC through the regulation of LSCC upstream regulators and downstream marker genes, which were involved in tumor cell proliferation and protein polyubiquitination/ubiquitination

The application of podocyte antigen PLA2R and anti-PLA2R antibody in the diagnosis and treatment of membranous nephropathy

The application of podocyte antigen M-type phospholipase A2 receptor (PLA2R, GAg) and serum anti-PLA2R antibody (SAb) in predicting the prognosis of membrane nephropathy (MN) was controversial. 328 biopsy-proven MN patients were divided into three phenotypes, 182 MN patients with GAg+/SAb+, 118 MN patients with GAg+/SAb-, and 28 MN patients with GAg-/SAb-. The baseline clinicopathological characteristics, therapy response, and prognosis were compared among the three groups. Cox regression analysis was performed to assess predictors of remission. Anti-PLA2R antibody was analyzed by receiver operating characteristic curve to find the optimal titer for MN diagnosis. Lower eGFR (p = 0.009), higher UPCR (p p p = 0.015 and p = 0.023, respectively). No significant difference was observed among the three groups in terms of complete remission, relapse, and developing ESRD. SAb+ status was an independent predictor for no remission (hazard ratio 1.378, 95% confidence interval 1.023 to 1.855; p = 0.035). The optimal cutoff value for anti-PLA2R antibody to predict MN was 2.055 RU/mL (sensibility 0.802, specificity 0.970). GAg+/SAb+ MN patients were related to more severe clinical manifestations and more requisition of immunosuppressive treatment. Positive anti-PLA2R antibody was an independent predictor for no remission. An anti-PLA2R antibody above 2.055 RU/mL can be a suggestive indicator of MN diagnosis in patients with proteinuria.</p