Changes in N-glycosylation on specific peptide sites of serum proteins have been investigated as potential markers for diagnosis of nonalcoholic steatohepatitis (NASH)-related HCC. To accomplish this work, a novel workflow involving broad-scale marker discovery in serum followed by targeted marker evaluation of these glycopeptides were combined. The workflow involved an LC-Stepped HCD-DDA-MS/ MS method coupled with offline peptide fractionation for large-scale identification of N-glycopeptides directly from pooled serum samples (each n = 10) as well as differential determination of N-glycosylation changes between disease states. We then evaluated several potentially diagnostic N-glycopeptides among 78 individual patient samples (40 cirrhosis, 28 early stage NASH HCC, and 10 late-stage NASH HCC) by LC-Stepped HCD-PRM-MS/MS to quantitatively analyze 65 targeted glycopeptides from 7 glycoproteins. Of these targets, we found site-specific N-glycopeptides n 169 GSLFAFR_HexNAc(4)Hex(5)-NeuAc(2) and n 242 ISDGFDGIPDNVDAALALPAHSYSGR_HexNAc(5)Hex( 6)Fuc(1)NeuAc(3) from VTNC were significantly increased comparing samples from patients with NASH cirrhosis and NASH HCC (p < 0.05). When combining results of these 2 glycopeptides with AFP, the ROC curve analysis demonstrated the AUC value increased to 0.834 (95% CI, 0.748−0.921) and 0.847 (95% CI, 0.766−0.932), respectively, as compared to that of AFP alone (AUC = 0.791, 95% CI, 0.690−0.892). These 2 glycopeptides may serve as potential biomarkers for early HCC diagnosis in patients with NASH related cirrhosis.

We detected disproportionate reports of premature ovarian insufficiency (POI) and related events, including amenorrhea, menstruation irregular, FSH increased, and premature menopause, following human papillomavirus (HPV) vaccine from FDA Vaccine Adverse Event Reporting System (VAERS). The signal was detected by the methods of Bayesian Confidence Propagation Neural Network (BCPNN) and Multi-item Gamma Poisson Shrinker (MGPS). When both methods detected a positive result, a signal was generated. Besides, time-scan map is drawn based on the IC value and 95%CI of BCPNN, if the IC curve showed a steady upward trend and the 95%CI narrowed, the signal was stable and strong association.The results showed that there were not POI reports of HPV vaccine, but VAERS received a total of 2, 389, 27 POI related events for HPV2, HPV4, HPV9 respectively from the year of marketed to 2018. No signal was detected for HPV2. HPV4-POI ralated events were all detected as signals by two methods. There was only one signal of menstruation irregular for HPV9. Time scan of HPV4-POI ralated events showed those signals were stability and strong association, but not for HPV9. Our results only represent statistical association between HPV vaccine and POI related events, causal relationship needs further investigation.

A leading cause of death worldwide is sepsis that develops as a dysregulated immune response to infection. Serious infection caused by methicillin-resistant Staphylococcus aureus (MRSA) increases the difficulty of treatment in septic patients. Host-directed therapy (HDT) is an emerging approach to bacterial infections. Xuebijing injection (XBJ), a commercialized injectable prescription from traditional Chinese medicine, has been used as adjuvant therapy for sepsis with a history of 15 years. Whether it plays a protective role in severe infection caused by antibiotic-resistant bacteria is still unknown. In this study, XBJ significantly improved the survival of MRSA-induced sepsis mice. In MRSA-infected mouse model, XBJ down-regulated the expression of inflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-a, MCP-1, MIP-2, and IL-10 in sera. Besides that, it decreased the bacterial load in spleens, livers, and alleviated tissue damage of lung, liver, and kidney. The combination of XBJ with vancomycin or dexamethasone exhibited a better down-regulatory role of the inflammatory response. Then, the protective mechanism of XBJ was further investigated. XBJ inhibited heatkilled MRSA-induced IL-6 and TNF-a production in mouse macrophages. XBJ also decreased Pam3CSK4 (a synthetic tripalmitoylated lipopeptide mimicking bacterial lipoproteins)stimulated expression of IL-6, TNF-a, IL-1b, IL-12, etc. in mouse macrophages. Furthermore, XBJ down-regulated the activation of NF-kB, MAPK, and PI3K/Akt pathways in Pam3CSK4-stimulated mouse macrophages. In conclusion, our findings demonstrated that XBJ played a protective role in MRSA-challenged mice and down-regulated the inflammatory response and the activation of signaling pathways initiated by Pam3CSK4. It enlarged the clinical application of XBJ in the treatment of severe bacterial infection, e.g. caused by MRSA.

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Coal fly ash (CFA) has gained increasing societal concerns as hazardous trace elements (HTEs) in CFA might pose environmental and public health risks. To develop better management and remediation strategies, it is highly important to obtain an in-depth understanding of the occurrence and mobility of HTEs in CFA. This study systematically characterized the speciation, distribution, and mobility of Cr, Ni, and Cu in class F and class C CFA samples using scanning electron microscopy with energydispersive X-ray spectroscopy (SEM−EDX), X-ray absorption near-edge spectroscopy (XANES), and sequential chemical extraction. SEM−EDX results show that Cr, Ni, and Cu are present in a range of 2−15 μm sized particles either as discrete particles or encapsulated in the glass phase. XANES results suggest that Cr is mainly present in Fe oxides or silicates and spinel minerals; Ni mainly in Fe oxides and as NiO; and Cu mainly as Cu 2 O/CuO or in Fe oxides. Cr(III) and Cu(I) are the dominant oxidation states for Cr and Cu, respectively. Sequential extraction generally shows higher mobility of trace elements (Cr, Mn, Co, Ni, Cu, Zn, Cd, and Pb) in class C CFA, as compared to the mobility of those in class F CFA, implying potentially higher environmental risks for class C CFA.