How the intestinal tract develops a tolerance to foreign antigens is still largely unknown. Here we report that extracellular vesicles (EVs) with TGF-β1-dependent immunosuppressive activity are produced by intestinal epithelial cells (IECs) under physiological conditions. Transfer of these EVs into inflammatory bowel disease (IBD) mice induced by dextran sulfate sodium salt decreases IBD severity by inducing regulatory T cells and immunosuppressive dendritic cells. In contrast, decreased endogenous EV production promotes IBD development. IECs produce EVs with increased levels of TGF-β1 upon IBD development in an ERK-dependent manner. Furthermore, these EVs tend to localize in the intestinal tract associated with epithelial cell adhesion molecule (EpCAM). Knockdown of EpCAM in vivo increases the severity of murine IBD, and the protective effect of EVs from IECs with decreased EpCAM on murine IBD is blunted. Therefore, our study indicates that EVs from IECs participate in maintaining the intestinal tract immune balance.

a b s t r a c tSince its outbreak in December 2019, a series of clinical trials on Coronavirus Disease 2019 have been registered or carried out. However, the significant heterogeneity and less critical outcomes of such trials may be leading to a waste of research resources. This study aimed to develop a core outcome set (COS) for clinical trials on COVID-19 in order to tackle the outcome issues. The study was conducted according to the Core Outcome Measures in Effectiveness Trials (COMET) handbook (version 1.0), a guideline for COS development. A research group was set up that included experts in respiratory and critical medicine, traditional Chinese medicine, evidence-based medicine, clinical pharmacology, and statistics, in addition to medical journal editors. Clinical trial registry websites (chictr.org.cn and clinicaltrials.gov) were searched to retrieve clinical trial protocols and outcomes in order to form an outcome pool. A total of 78 clinical trial protocols on COVID-19 were included and 259 outcomes were collected. After standardization, 132 outcomes were identified within seven different categories, of which 58 were selected to develop a preliminary outcome list for further consensus. After two rounds of Delphi survey and one consensus meeting, the most important outcomes for the different clinical classifications of COVID-19 were identified and determined to constitute the COS for clinical trials on COVID-19 (COS-COVID). The COS-COVID includes one outcome for the mild type (time to 2019-nCoV reverse transcriptionpolymerase chain reaction (RT-PCR) negativity), four outcomes for the ordinary type (length of hospital

PurposeThe purpose of this paper is to explore knowledge sharing in a Chinese context and to examine the impact of some key contextual factors that affect knowledge sharing within project teams in the Chinese construction sector.Design/methodology/approachSelf‐administered questionnaires were used in this study. Data were collected by surveying 222 managerial employees from different project teams in the construction sector in China. Regression analysis was then used to explore the relationship between different factors and the willingness to share knowledge. The potential influence of Chinese traditional cultures on this relationship was also explored.FindingsThis paper shows that within the Chinese context, explicit knowledge promotes knowledge sharing while tacit knowledge creates barriers to knowledge sharing in project teams. Moreover, trust is positively related to knowledge sharing but justice, leadership style, and empowerment do not influence whether employees will share knowledge among themselves in project teams.Originality/valueWhile it is well known that knowledge management is critical to success, few studies have examined knowledge management in a Chinese context and little is known how the Chinese generate, codify, and transfer knowledge. This paper tries to bridge this gap by examining what affects knowledge sharing in project teams in China so as to help better understand knowledge management in this important emerging market and whether China can sustain its success in economic growth with effective knowledge management.

No abstract

Invasive fungal infections kill more than 1.5 million people each year, with limited treatment options. There is no vaccine available in clinical use to prevent and control fungal infections. Our recent studies showed that a mutant of the F-box protein Fbp1, a subunit of the SCF(Fbp1) E3 ligase in Cryptococcus neoformans, elicited superior protective Th1 host immunity. Here, we demonstrate that the heat-killed fbp1Δ cells (HK-fbp1) can be harnessed to confer protection against a challenge by the virulent parental strain, even in animals depleted of CD4+ T cells. This finding is particularly important in the context of HIV/AIDS-induced immune deficiency. Moreover, we observed that HK-fbp1 vaccination induces significant cross-protection against challenge with diverse invasive fungal pathogens. Thus, our data suggest that HK-fbp1 has the potential to be a broad-spectrum vaccine candidate against invasive fungal infections in both immunocompetent and immunocompromised populations.

Lectin affinity chromatography was miniaturized into a microfluidic format, which results in improvement of performance, as compared to the conventional method. A lectin affinity monolith column was prepared in the microchannel of a microfluidic chip. The porous monolith was fabricated by UV-initiated polymerization of ethylene dimethacrylate (EDMA) and glycidyl methacrylate (GMA) in the presence of porogeneities, followed by immobilization of pisum sativum agglutinin (PSA) on the monolith matrix. Using electroosmosis as the driven force, lectin affinity chromatographies of three kinds of glycoprotein, turkey ovalbumin (TO), chicken ovalbumin (CO), and ovomucoid (OM), were carried out on the microfluidic system. All the glycoproteins were successfully separated into several fractions with different affinities toward the immobilized PSA. The integrated system reduces the time required for the lectin affinity chromatography reaction to ∼3%, thus, the overall analysis time from 4 h to 400 s. Only 300 pg of glycoprotein is required for the whole separation process. Moreover, troublesome operations for lectin affinity chromatography are simplified.The carbohydrate moiety of a glycoprotein may affect the immunogeneity, half-life, bioactivity, and stability of a potential therapeutic product. 1 Protein glycosylation can occur at two or more positions in the amino acid sequence, and the glycans at even a single position may be heterogeneous or may be missing from some molecules. This leads to the populations of glycosylated variants of a single protein, usually referred to as glycoforms, whose relative proportions are found to be reproducible and not random. However, the glycoforms may be affected by several factors, including the environment in which the protein is glycosylated, the manufacturing process, and the isolation procedures. 2 Therefore, glycoform separation and resolution are critical to understand the structure, function, and heterogeneity of the glycosyl groups on proteins. 3 Lectins by definition are multivalent proteins of nonimmune origin that bind to sugars rather specifically and agglutinate cells. 4 The ability of lectins to probe variations in carbohydrate structures on cell surface glycoproteins and glycolipids has made them a paradigm for protein/carbohydrate recognition. Immobilized lectins have been used to select glycoprotein from biological extracts on the basis of the glycosylation found in the protein. 5 Lectin column has also been particularly useful in characterization of glycoforms and oligosaccharides from glycoproteins. 4,6-9 Highmannose-type, complex-type, and hybrid-type sugar chains have been fractionated by using immobilized lectin columns in series, each with a different binding affinity for the various glycoforms. 10 Fractionation within a class can be accomplished by gradient elution of a specific column with increasing concentrations of a displacing agent. 11 Lectin affinity chromatography (LAC) 5,6 is one of the most useful techniques. LAC can separate the glycoforms in...

Dexamethasone can reduce the endotoxin level and inflammatory mediators and down-regulate NF-kappaB protein expression of ileum mucosa, and ileum mucosa epithelial cell apoptosis induction was involved as well. The tissue microarrays technique is of advantage in SAP study.

Circular RNAs are a new class of non-coding RNAs that have been shown to play critical roles in the development and progression of renal cell carcinoma (RCC). However, little is known about the functional mechanisms and therapeutic role of ciRS-7 in RCC. A series of in vitro and in vivo experiments were performed to investigate the functional mechanism and therapeutic role of ciRS-7, such as real-time quantitative PCR, CCK-8, wound healing, transwell, colony formation, Edu, tumor xenograft and lung metastasis in NSG mice. RNA pull-down, dual luciferase reporter, fluorescence in situ hybridization (FISH) and rescue assays were used to determine the relationship between ciRS-7, miR-139-3p and TAGLN. In addition, we constructed PBAE/si-ciRS-7 nanocomplexes with PBAE material to evaluate the therapeutic effect of the nanocomplexes on tumor in vivo. ciRS-7 was highly expressed in RCC tumor tissues and cell lines, and high ciRS-7 expression correlated with tumor size, high Fuhrman grade and poor survival. Depletion of ciRS-7 significantly inhibited RCC cell proliferation, invasion, tumor growth and metastasis in vivo, while overexpression of ciRS-7 had the opposite effect. Mechanistically, ciRS-7 acts as a "ceRNA" for miR-139-3p to prevent TAGLN degradation and promoting RCC progression and metastasis via the PI3K/AKT signaling pathway. In addition, miR-139-3p mimics or inhibitor could reverse the altered malignant tumor behavior caused by ciRS-7 overexpression or silencing. Furthermore, the PBAE/siciRS-7 nanocomplexes could significantly inhibit RCC tumor progression and metastasis in vivo. ciRS-7 acts as a tumor promoter by regulating the miR-139-3p/TAGLN axis and activating the PI3K/AKT signaling pathway to promote RCC progression and metastasis. Drug development of PBAE/si-ciRS-7 nanocomplexes targeting ciRS-7 may represent a promising gene therapeutic strategy for RCC.