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NLRC5 has been reported to be involved in antiviral immunity; however, the underlying mechanism remains poorly understood. Here, we investigated the functional role of NLRC5 in the infection of a flavivirus, dengue virus (DENV). We found that the expression of NLRC5 was strongly induced by virus infection and IFNB or IFNG stimulation in different cell lines. Overexpression of NLRC5 remarkably suppressed DENV infection, whereas knockout of NLRC5 led to a significant increase in DENV infection. Mechanistic study revealed that NLRC5 interacted with the viral nonstructural protein 3 (NS3) protease domain and mediated degradation of NS3 through a ubiquitin-dependent selective macroautophagy/autophagy pathway. We demonstrated that NLRC5 recruited the E3 ubiquitin ligase CUL2 (cullin 2) to catalyze K48-linked poly-ubiquitination of the NS3 protease domain, which subsequently served as a recognition signal for cargo receptor TOLLIP-mediated selective autophagic degradation. Together, we have demonstrated that NLRC5 exerted an antiviral effect by mediating the degradation of a multifunctional protein of DENV, providing a novel antiviral signal axis of NLRC5-CUL2-NS3-TOLLIP. This study expands our understanding of the regulatory network of NLRC5 in the host defense against virus infection. [ABSTRACT FROM AUTHOR]

Curcumin (Cur) is a natural active phenolic compound extracted from the root of Curcuma Longa L. It has anti‐inflammatory, anti‐tumor and other pharmacological activities, and is commonly used to treat ulcerative colitis (UC). However, it is not clear whether curcumin regulates the function and differentiation of Breg cells to treat UC. In this study, mice with chronic colitis were induced by dextran sulfate sodium (DSS), and treated with curcumin for 12 days. Curcumin effectively improved the body weight, colonic weight, colonic length, decreased colonic weight index and pathological injury score under colonoscopy in mice with chronic colitis, and significantly inhibited the production of IL‐1β, IL‐6, IL‐33, CCL‐2, IFN‐γ, TNF‐α, and promoted the secretion of IL‐4, IL‐10, IL‐13 and IgA. Importantly, curcumin markedly upregulated CD3−CD19+CD1d+, CD3−CD19+CD25+, CD3−CD19+Foxp3+Breg cells level and significantly down‐regulated CD3−CD19+PD‐L1+, CD3−CD19+tim‐1+, CD3−CD19+ CD27+ Breg cells level. In addition, our results also showed that curcumin observably inhibited TLR2, TLR4, TLR5, MyD88, IRAK4, p‐IRAK4, NF‐κB P65, IRAK1, TRAF6, TAB1, TAB2, TAK1, MKK3, MKK6, p38MAPK, p‐p38MAPK and CREB expression in TLR/MyD88 signaling pathway. These results suggest that curcumin can regulate the differentiation and function of Breg cell to alleviate DSS‐induced colitis, which may be realized by inhibiting TLR/MyD88 pathway. [ABSTRACT FROM AUTHOR]

Freeze-drying (FD) is often used for therapeutic proteins and other biological drugs to extend their shelf life, but it usually reduces the activity and stability of the protein and has a longer drying cycle. A microwave-assisted freeze-drying (MFD) was proposed to produce immunoglobulin of yolk (IgY) preparations. The effects of FD and MFD on the immunological activity and structure of IgY with different amounts of trehalose were investigated. Results showed that lyophilization led to a partial loss of secondary structure in IgY, which resulted in the activity loss. As the trehalose content increased from 0% to 5%, the activity retention of MFD samples increased from 20.31% to 75.57%, which was comparable to FD samples (from 23.57% to 67.78%). However, MFD had a shorter drying cycle when compared with FD. MFD can be a potential alternative to FD as a common therapeutic protein drying method. [ABSTRACT FROM AUTHOR]

Simple Summary: CXC chemokines are small molecules and secretory peptides, which are significantly associated with cancer progression. Aberrant expression of CXC chemokines is always observed in cancer patients. An increasing number of studies have reported that CXC chemokines play essential roles in tumor angiogenesis, tumor-promoting inflammation, and metastasis, which favor cancer promotion. The expression level of CXC chemokines is closely associated with the clinicopathological characteristics and outcomes of cancer. The specific roles of CXC chemokines and corresponding signaling pathways in cancer progression are summarized in this review. Furthermore, we have discussed the potential application of CXC chemokines for cancer targeted therapy and personalized treatment. CXC chemokines are small chemotactic and secreted cytokines. Studies have shown that CXC chemokines are dysregulated in multiple types of cancer and are closely correlated with tumor progression. The CXC chemokine family has a dual function in tumor development, either tumor-promoting or tumor-suppressive depending on the context of cellular signaling. Recent evidence highlights the pro-tumorigenic properties of CXC chemokines in most human cancers. CXC chemokines were found to play pivotal roles in promoting angiogenesis, stimulating inflammatory responses, and facilitating tumor metastases. Enhanced expression of CXC chemokines is always signatured with inferior survival and prognosis. The levels of CXC chemokines in cancer patients are in dynamic change according to the tumor contexts (e.g., chemotherapy resistance and tumor recurrence after surgery). Thus, CXC chemokines have great potential to be used as diagnostic and prognostic biomarkers and therapeutic targets. Currently, the molecular mechanisms underlying the effect of CXC chemokines on tumor inflammation and metastasis remain unclear and application of antagonists and neutralizing antibodies of CXC chemokines signaling for cancer therapy is still not fully established. This article will review the roles of CXC chemokines in promoting tumorigenesis and progression and address the future research directions of CXC chemokines for cancer treatment. [ABSTRACT FROM AUTHOR]

Our objective was to identify the optimal method to assess reduced muscle mass (RMM) using the Global Leadership Initiative on Malnutrition (GLIM) approach and investigate the roles of the GLIM approach in nutrition assessment and survival prediction in colorectal cancer (CRC) patients. During a median follow-up period of 4.2 (4.0, 4.4) years, a development cohort of 3612 CRC patients with a mean age of 64.09 ± 12.45 years was observed, as well as an external validation cohort of 875 CRC patients. Kaplan–Meier curves and multivariate Cox regression were adopted to analyze the association between GLIM-diagnosed malnutrition and the overall survival (OS) of CRC patients. A nomogram predicting individualized survival was constructed based on independent prognostic predictors. The concordance index, calibration curve, and decision curve were applied to appraise the discrimination, accuracy, and clinical efficacy of the nomogram, respectively. Patients diagnosed with severe malnutrition based on either the mid-arm muscle circumference (MAMC) or body weight-standardized hand grip strength (HGS/W) method had the highest mortality hazard ratio (HR, 1.51; 95% CI, 1.34–1.70; p < 0.001). GLIM-defined malnutrition was diagnosed in 47.6% of patients. Severe malnutrition was an independent mortality risk factor for OS (HR, 1.25; 95% CI, 1.10–1.42; p < 0.001). The GLIM nomogram showed good performance in predicting the survival of CRC patients and was clinically beneficial. Our findings support the effectiveness of GLIM in diagnosing malnutrition and predicting OS in CRC patients. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel ratio fluorescence sensor was developed by simply mixing. • The sensor is used to detect Pb2+ with high specificity and sensitivity. • Portable detection platform integrated with smartphone-assisted ratiometric fluorescence sensor for visual on-site detection of lead(Ⅱ). Lead ion (Pb2+) pollution seriously threatens the quality of aquatic products. In this study, a ratiometric fluorescence sensor consisting of tangerine fluorescent Mn:ZnS QDs (T-QDs) and blue fluorescent Fe-MOF (B-MOF) was developed for selective recognition of Pb2+. Upon exposure to Pb2+, the fluorescence of T-QDs was quenched while the fluorescence of B-QDs was slightly changed, causing the changes of fluorescence colors from tangerine to blue with a detection limit (LOD) of 3.79 nmol/L. The sensor also had the strengths of low cost, easy to operate, excellent sensitivity and selectivity. Significantly, a portable detection platform integrated with the sensor was constructed to achieve on-site visual detection. As expected, the detection platform was successfully applied for testing Pb2+ with the LOD of 7.78 nmol/L. The strategy may not only provide a great capacity for on-site monitoring of Pb2+ in aquatic products but also expand application in environmental pollution detection. [ABSTRACT FROM AUTHOR]