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We report here the first gold-catalyzed nitrene transfer reaction. A gold(I) compound, supported by 4,4',4' '-tri-tert-butyl-2,2':6',2' '-terpyridine (tBu3tpy) as the ligand, efficiently catalyzes olefin aziridination with the use of the commercially available oxidant PhI(OAc)2 and sulfonamides. This system also mediates carbene insertion into benzene.

Abstract. Th1 antigen-specific T cells secrete interferon-γ, which is able to kill antigen-specific cancer cells and is helpful for cancer vaccines. The aim of the present study was to explore whether B16 cell lysates plus polyinosinic-cytidylic acid (poly I:C) can effectively inhibit the progression of melanoma in an animal model. In the present study, C57BL/6 mice were divided into three groups, with each group containing more than six mice. The groups of mice were immunized twice with B16 cell lysates plus poly I:C, B16 cell lysates, or phosphate-buffered saline only, respectively. The in vivo results demonstrated that splenocytes from the mice immunized with B16 cell lysates plus poly I:C contained higher percentages of CD3 + CD8 + T lymphocytes and CD3 + CD4 + T lymphocytes, which were detected by a fluorescence-activated cell sorter, and produced higher levels of antigen-specific splenocyte proliferation activity, as detected by MTT assay. The splenocytes from the mice immunized with B16 cell lysates in combination with poly I:C produced higher levels of interferon-γ, as detected by quantitative polymerase chain reaction and ELISA, as well as cytotoxic T lymphocyte activity when stimulated in vitro with B16 lysates. Additionally, subcutaneous immunization of the C57BL/6 mice with B16 cell lysates plus poly I:C conferred greater protection against tumor-forming B16 melanoma cells than that of the mice immunized with injection of B16 cell lysate alone. In conclusion, the cancer vaccine of B16 cell lysates plus poly I:C exerts potently protective effects that polarize responses toward Th1 and elicit antitumor immunity. IntroductionMalignant melanoma is a serious disease arising from melanocytes which threatens human health in China and worldwide (1,2). The incidence and mortality rate of malignant melanoma continues to increase at a higher rate than that of any other type of malignancy (3,4). Although melanoma is curable if detected at an early localized stage, metastatic malignant melanoma has already become a therapeutic challenge (5). Hundreds of patients with advanced stage III or IV melanoma, particularly those with metastatic disease, have participated in studies of immunological therapy having failed on chemotherapy (6). Thus, ways to prevent and treat malignant melanoma using immunological methods are urgently required. Vaccination has been used for centuries, causing mortality due to infectious disease in humans to profoundly decrease, but a number of serious global diseases with no effective vaccines remain, including acquired immunodeficiency syndrome, influenza, malaria and cancer. It is harder to produce effective immune responses when using vaccines as a treatment for cancer, compared with when using preventive cancer vaccines (7,8). The cancer vaccine for cervical tumors is the first vaccine to prevent human cancer. With the success of the cervical cancer vaccine, an increasing number of researchers have been working to identify novel and effective cancer vaccines. Thus, the aim of the present ...

Neonatal sepsis (NS) remains a major cause of morbidity and mortality in neonates, but data on the etiology and antibiotic susceptibility patterns of pathogens are limited. The aim of this study was to analyze the clinical characteristics, risk factors, and the antibiotic susceptibility patterns of pathogenic microbes associated with NS at a tertiary children's hospital in Shanghai, China. Episodes of blood culture-proven sepsis in the neonatal intensive care unit (NICU) of Children's Hospital of Fudan University from January 2013 to August 2017 were retrospectively reviewed. Collected data included demographics, perinatal risk factors, clinical symptoms, laboratory values, microbiology results and their antimicrobial susceptibility. Data for early-onset neonatal sepsis (EONS) and late-onset neonatal sepsis (LONS) were compared. The 341 of 976 culture-positive cases were selected, including 161 EONS cases (47.21% of 341) and 180 LONS cases (52.79% of 341). 635 incomplete cases were excluded. There was significant difference in risk factors between the EONS group and LONS group including birth weight, gestational age, 1-minute Apgar score, respiratory support, and the use of peripherally insertion central catheter (PICC). Clinical symptoms such as fever, feeding intolerance, abdominal distension, and neonatal jaundice, and laboratory results such as hemoglobin and lymphocyte counts also showed between-group differences. Staphylococcus epidermidis (22.87%) , Escherichia coli (9.68%), Alcaligenes xylosoxidans (9.38%) and Klebsiella pneumoniae (9.09%) remain the principal organisms responsible for neonatal sepsis. Most isolates of Gram-positive bacteria were sensitive to vancomycin, linezolid, minocycline and tigecycline, of which more than 90% were resistant to penicillin. Most isolates of Gram-negative bacteria were sensitive to amikacin and imipenem and resistant to ampicillin. Fungus was sensitive to antifungal agents. Better medical decisions, especially early detection and appropriate initial antimicrobial therapy can be made after understanding the different clinical features and pathogens of EONS and LONS.

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Genetic engineering (GE) technology is widely used in plant modification. However, the results of modification may not exactly meet the expectations. Herein, we propose a new multi-omics method for GE plant evaluation based on the optimized use of the metID algorithm. Using this method, we found that flavonoid accumulation was at the expense of the great sacrifice of Lphenylalanine in GE tomatoes for the first time. Meanwhile, the ceramide series of sphingolipid is synthesized de novo from L-serine, and ceramides are the primary source of vesicles coated with flavonoids and secreted from the endoplasmic reticulum. Therefore, the accumulation of the ceramide series of sphingolipid changed the cell component of intracellular organelles. Furthermore, the improvement of the method allows us to identify more metabolites related to dysregulated pathways.

The acquisition of metastasis potential is a critical point for malignant tumors. Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) is a potential tumor suppress gene and frequently down-regulated in malignant tumors. It has been implicated that overexpression of MDA-7 led to proliferation inhibition in many types of human tumor. Invasion is an important process which is potential to promote tumor metastasis. However, the role and potential molecular mechanism of mda-7/IL-24 to inhibit the invasion of human melanoma cancer is not fully clear. In this report, we identified a solid role for mda-7/IL-24 in invasion inhibition of human melanoma cancer LiBr cells, including decreasing of adhesion and invasion in vitro, blocking cell cycle, down-regulating the expression of ICAM-1, MMP-2/9, CDK1, the phosphorylation of ERK and Akt, NF-κB and AP-1 transcription activity. Meanwhile, there was an increased expression of PTEN in mda-7/IL-24 over-expression LiBr cells. Our results demonstrated that mda-7/IL-24 is a potential invasion suppress gene, which inhibits the invasion of LiBr cells by the down-regulation of ICAM-1, MMP-2/9, PTEN, and CDK1 expression. The molecular pathways involved were the MAPK/ERK, PI3K-Akt, NF-κB, and AP-1. These findings suggest that mda-7/IL-24 may be used as a possible therapeutic strategy for human melanoma cancer.

Melanoma is a malignant tumor. The acquisition of stemness by melanoma cells aggravates the malignant transformation, which can be regulated by microRNAs (miRNAs, miR). MiR-363-3p is a key tumor-related miRNA, but its role in stemness and melanoma cells is still unknown. Presently, miR-363-3p induced by hypoxia inducible factor (HIF)-2α has a positive role in melanoma cell stemness. The levels of miR-363-3p and HIF-2α are upregulated in melanoma cell lines. Overexpression of HIF-2α significantly increased levels of miR-363-3p. However, both HIF-2α knockdown and miR-363-3p inhibition decreased the levels of stemness markers (CD133, CD271, Jarid1B and Nanog). Furthermore, the levels of miR-363-3p and HIF-2α were upregulated in fluorescence activated cell sorting (FACS)-sorted CD271 high/+ cells. Whereas, miR-363-3p depletion reduced the proportion and the ability of the CD271 high/+ cells to form spheroids, decreased the levels of CD133, CD271, Jarid1B and Nanog with restrained proliferative activity of CD271 high/+ cells. Additionally, miR-363-3p was confirmed a key downstream effector of HIF-2α. Intriguingly, cyclin-dependent kinase inhibitor 1A [CDKN1A, p21(Cip1/Waf1)], a key inhibitor of S-phase DNA synthesis and cell cycle progression, was confirmed a target gene of miR-363-3p by luciferase reporter gene assay. The protein levels of CD133, CD271, Jarid1B and Nanog were upregulated with enhanced proliferative activity of CD271 high/+ cells by inhibition of p21 in melanoma cells. In conclusion, miR-363-3p is induced by HIF-2α to promote stemness of melanoma cells via inhibiting p21. The present study provides novel insights and indicates that HIF-2α/miR-363-3p/p21 signaling may be a potential target in melanoma research and therapy.