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Interferon (IFN) responses are central to host defense against coronavirus and other virus infections. Manganese (Mn) is capable of inducing IFN production, but its applications are limited by nonspecific distributions and neurotoxicity. Here, we exploit chemical engineering strategy to fabricate a nanodepot of manganese (nanoMn) based on Mn2+. Compared with free Mn2+, nanoMn enhances cellular uptake and persistent release of Mn2+ in a pH-sensitive manner, thus strengthening IFN response and eliciting broad-spectrum antiviral effects in vitro and in vivo. Preferentially phagocytosed by macrophages, nanoMn promotes M1 macrophage polarization and recruits monocytes into inflammatory foci, eventually augmenting antiviral immunity and ameliorating coronavirus-induced tissue damage. Besides, nanoMn can also potentiate the development of virus-specific memory T cells and host adaptive immunity through facilitating antigen presentation, suggesting its potential as a vaccine adjuvant. Pharmacokinetic and safety evaluations uncover that nanoMn treatment hardly induces neuroinflammation through limiting neuronal accumulation of manganese. Therefore, nanoMn offers a simple, safe, and robust nanoparticle-based strategy against coronavirus. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s12274-020-3243-5 and is accessible for authorized users.

Background Platinum‐based chemotherapy is effective in inducing shrinkage of primary lung cancer lesions; however, it shows finite therapeutic efficacy in patients suffering from brain metastasis (BM). The intrinsic changes of BM cells, which contribute to the poor results remain unknown. Methods Platinum drug‐sensitivity was assessed by utilizing a preclinical BM model of PC9 lung adenocarcinoma cells in vitro and in vivo. High consumption of glutathione (GSH) and two associated upregulated proteins (GPX4 and GSTM1) in BM were identified by integrated metabolomics and proteomics in cell lines and verified by clinical serum sample. Gain‐of‐function and rescue experiments were implemented to reveal the impact and mechanism of GPX4 and GSTM1 on the chemosensitivity in BM. The interaction between GPX4 and GSTM1 was examined by immunoblotting and immunoprecipitation. The mechanism of upregulation of GPX4 was further uncovered by luciferase reporter assay, immunoprecipitation, and electrophoretic mobility shift assay. Results The derivative brain metastatic subpopulations (PC9‐BrMs) of parental cells PC9 developed obvious resistance to platinum. Radically altered profiles of BM metabolism and protein expression compared with primary lung cancer cells were described and GPX4 and GSTM1 were identified as being responsible for the high consumption of GSH, leading to decreased chemosensitivity by negatively regulating ferroptosis. Besides, GSTM1 was found regulated by GPX4, which was transcriptionally activated by the Wnt/NR2F2 signaling axis in BM. Conclusions Collectively, our findings demonstrated that Wnt/NR2F2/GPX4 promoted acquired chemoresistance by suppressing ferroptosis with high consumption of GSH. GPX4 inhibitor was found to augment the anticancer effect of platinum drugs in lung cancer BM, providing novel strategies for lung cancer patients with BM., Wnt/NR2F2/GPX4 promoted acquired chemo‐resistance by suppressing ferroptosis with high consumption of GSH and GPX4 inhibitor was found to enhance the anticancer effect of platinum drugs in lung cancer BM, providing novel strategies for lung cancer patients with BM

High levels (> 100 ug/L) of arsenic are known to cause lung cancer; however, whether low (≤ 10 ug/L) and medium (10 to 100 ug/L) doses of arsenic will cause lung cancer or other lung diseases, and whether arsenic has dose-dependent or threshold effects, remains unknown. Summarizing the results of previous studies, we infer that low- and medium-concentration arsenic cause lung diseases in a dose-dependent manner. Arsenic trioxide (ATO) is recognized as a chemotherapeutic drug for acute promyelocytic leukemia (APL), also having a significant effect on lung cancer. The anti-lung cancer mechanisms of ATO include inhibition of proliferation, promotion of apoptosis, anti-angiogenesis, and inhibition of tumor metastasis. In this review, we summarized the role of arsenic in lung disease from both pathogenic and therapeutic perspectives. Understanding the paradoxical effects of arsenic in the lungs may provide some ideas for further research on the occurrence and treatment of lung diseases.

Migraine is a highly disabling primary headache associated with a high socioeconomic burden and a generally high prevalence. The clinical management of migraine remains a challenge. This study was undertaken to identify potential serum biomarkers of migraine. Using Liquid Chromatography coupled to Mass Spectrometry (LC-MS), the metabolomic profile of migraine was compared with healthy individuals. Principal component analysis (PCA) and Orthogonal partial least squares-discriminant analysis (orthoPLS-DA) showed the metabolomic profile of migraine is distinguishable from controls. Volcano plot analysis identified 10 serum metabolites significantly decreased during migraine. One of these was serotonin, and the other 9 were amino acids. Pathway analysis and enrichment analysis showed tryptophan metabolism (serotonin metabolism), arginine and proline metabolism, and aminoacyl-tRNA biosynthesis are the three most prominently altered pathways in migraine. ROC curve analysis indicated Glycyl-l-proline, N-Methyl-dl-Alanine and l-Methionine are potential sensitive and specific biomarkers for migraine. Our results show Glycyl-l-proline, N-Methyl-dl-Alanine and l-Methionine may be as specific or more specific for migraine than serotonin which is the traditional biomarker of migraine. We propose that therapeutic manipulation of these metabolites or metabolic pathways may be helpful in the prevention and treatment of migraine.

BACKGROUND Nitrobenzene (NB) is a persistent environmental pollutant difficult to degrade. The aim of this study was to accelerate the reduction of NB by immobilization of nanoscale zero-valent iron (NZVI) on an organobentonite (CTMA-Bent). RESULTS Batch experiments indicated that NB was almost completely reduced by the immobilized iron sample (NZVI/CTMA-Bent), with aniline as the dominant reduction product. While only 60% of NB was reduced by the bare NZVI, and aniline accounted for only half of the NB reduced. Kinetic studies confirmed that the reaction of NB with NZVI was accelerated through CTMA-Bent adsorption. XPS investigations suggested that the improved recycling of the NZVI/CTMA-Bent composite is related to less ferric (hydr)oxides formed during the reaction. CONCLUSION Immobilization of NZVI on the organobentonite CTMA-Bent proved to be an effective method for quick and complete conversion of NB to biodegradable aniline. This novel method to remove recalcitrant organic pollutants may promote the industrial application of NZVI technique in environmental remediation. © 2013 Society of Chemical Industry

Lactic acid bacteria that can produce alpha-galactosidase are a promising solution for improving the nutritional value of soy-derived products. For their commercial use in the manufacturing process, it is essential to understand the catabolic mechanisms that facilitate their growth and performance. In this study, we used comparative proteomic analysis to compare catabolism in an engineered isolate of Lactobacillus plantarum P-8 with enhanced raffinose metabolic capacity, with the parent (or wild-type) isolate from which it was derived. When growing on semi-defined medium with raffinose, a total of one hundred and twenty-five proteins were significantly up-regulated (>1.5 fold, P P de novo fatty acid biosynthesis and modification of existing lipid membrane phospholipid acyl chains. Interestingly, aspartate and glutamate metabolism was associated with this acid response. Higher intracellular aspartate and glutamate levels in the engineered isolate compared with the parent isolate were confirmed by further chemical analysis. Our study will underpin the future use of this engineered isolate in the manufacture of soymilk products.

In order to explore whether NF-κB activation correlates to the prognosis, chemoresistance, and sex hormone receptors status in ovarian serous carcinoma, we analyzed the expression of NF-κB, ER, and PR by immunohistochemistry in 72 cases of ovarian serous carcinoma, investigated the association among these markers, and evaluated their relations to clinicopathologic factors and prognosis. The positive rates were 88.9% for NF-κB cytoplasmic expression, 45.8% for NF-κB nuclear expression, 41.7% for ER, and 29.2% for PR. NF-κB nuclear expression was positively correlated with the 4th edition WHO grade (P=0.045) and tumor stage (P=0.001). NF-κB cytoplasmic expression was associated with preoperative serum CA125 level (P=0.015) and ascites (P=0.042). Neither cytoplasmic nor nuclear staining of NF-κB showed any association with survival. PR expression was correlated with tumor stage (P=0.023) and omental metastasis (P=0.022). Omental metastasis occurred more frequently in ER-/PR- tumors (P=0.009). No correlation between NF-κB expression and ER, PR expression was observed. In conclusion, in ovarian serous carcinoma, NF-κB nuclear expression correlated with the 4th edition WHO grade and PR was a favorable prognostic factor for ovarian serous carcinoma.

G protein plays an important role in signaling pathways and is involved in various signal transduction systems in plant. A full-length cDNA encoding a putative G protein γ subunit (Gγ), designated as BnGG2, was isolated from Brassica napus L. BnGG2 is predicted to encode a precursor protein of 100 amino acid residues. The expression of BnGG2 in different B. napus tissues and developmental stages was analyzed by using real-time PCR. The results showed that BnGG2 expression level was high at the 7-day-old seedling stage, the bolting stage, and the fruiting stage. Moreover, BnGG2 was analyzed under four different plant hormones. All of the four tested hormones, abscisic acid (ABA), gibberellins acid 3 (GA3), brassinosteroid (BR) and indole-3-acetic acid (IAA), triggered an induction of BnGG2 expression at different hormone concentrations. The expression of BnGG2 was significantly induced by the high concentrations of ABA, BR, and IAA. The expression of BnGG2 was also induced by low GA3 concentrations and inhibited by high GA3 concentrations. In addition, BnGG2 was responsive to different abiotic stresses. The BnGG2 was up-regulated in salt and drought stress and down-regulated in heat and cold stress. These results suggested that BnGG2 plays an important role in plant hormone signaling pathways and may be also involved in plant defense systems against environmental stresses in B. napus.

G protein plays an important role in signaling pathways and is involved in various signal transduction systems in plant. A full-length cDNA encoding a putative G protein γ subunit (Gγ), designated as BnGG2, was isolated from Brassica napus L. BnGG2 is predicted to encode a precursor protein of 100 amino acid residues. The expression of BnGG2 in different B. napus tissues and developmental stages was analyzed by using real-time PCR. The results showed that BnGG2 expression level was high at the 7-day-old seedling stage, the bolting stage, and the fruiting stage. Moreover, BnGG2 was analyzed under four different plant hormones. All of the four tested hormones, abscisic acid (ABA), gibberellins acid 3 (GA3), brassinosteroid (BR) and indole-3-acetic acid (IAA), triggered an induction of BnGG2 expression at different hormone concentrations. The expression of BnGG2 was significantly induced by the high concentrations of ABA, BR, and IAA. The expression of BnGG2 was also induced by low GA3 concentrations and inhibited by high GA3 concentrations. In addition, BnGG2 was responsive to different abiotic stresses. The BnGG2 was up-regulated in salt and drought stress and down-regulated in heat and cold stress. These results suggested that BnGG2 plays an important role in plant hormone signaling pathways and may be also involved in plant defense systems against environmental stresses in B. napus.

G protein plays an important role in signal pathways and involved in various signal transduction systems in plant. A full-length cDNA encoding a putative G protein α subunit (Gα), designated as BnGA1, was isolated from Brassica napus. The expression of BnGA1 in different B. napus tissues and developmental stags was analyzed using real-time PCR. The results showed that BnGA1 expressed was high in root, cotyledon and shoot apex. Stage expression pattern analysis revealed that BnGA1 expressed strongly at the 7th day, the bolting stage and fruiting stage. In addition, the expression of BnGA1 was analyzed under different concentrations of four plant hormones. The expression of BnGA1 was significantly induced by the high concentrations of abscisic acid (ABA) and brassinosteroid (BR). The expression of BnGA1 was also induced by low gibberellins acid 3 (GA(3)) concentrations and higher GA(3) concentrations inhibit the expression of BnGA1. However, the expression of BnGA1 did not significantly regulated by exogenous indole-3-acetic acid (IAA). Moreover, the expression of BnGA1 under different abiotic stresses was analyzed at different time points. The BnGA1 was up-regulated in salt and drought stress and down-regulated in heat and cold stress. These expression results suggested that BnGA1 play an important role in plant hormones signal pathways and BnGA1 may be involved in plant defense system against environmental stresses in B. napus.

F-box protein family is characterized by an F-box motif that has been shown to be critical for the controlled degradation of regulatory proteins. In plant, F-box protein plays an important role in signal pathways and involved in various signal transduction systems. A full-length cDNA encoding a putative F-box protein, designated as BnSLY1, was isolated from Brassica napus. The full-length cDNA of BnSLY1 was 809 bp containing a 438 bp open reading frame encoding a precursor protein of 138 amino acid residues. Comparative and bioinformatic analyses revealed that BnSLY1 showed high degree of homology with F-box proteins from other plant species and contained F-box, GGF and LSL conserved motifs. The expression of BnSLY1 under exogenous gibberellins acid-3 (GA3), abscisic acid (ABA) and GA biosynthetic inhibitor paclobutrazol (PAC) was analyzed using real-time PCR. The results showed that the expression of BnSLY1 was down-regulated after GA3 treatment and prominently induced by ABA in the low concentrations. Moreover, BnSLY1 was also induction in the high concentrations of PAC. These results suggest that the expression of BnSLY1 was regulated by the exogenous GA3, ABA and PAC and may be related to endogenous level of GA in B. napus.