Purpose Adoptive transfer of natural killer (NK) cells combined with tumor-specific monoclonal antibodies (mAbs) has therapeutic potential for malignancies. We determined if large numbers of activated NK (aNK) cells can be grown ex vivo from peripheral blood mononuclear cells (PBMC) of children with high-risk neuroblastoma using artificial antigen-presenting cells (aAPC). Experimental Design Irradiated K562-derived Clone 9.mbIL21 aAPC were co-cultured with PBMC, and propagated NK cells were characterized with flow cytometry, cytotoxicity assays, Luminex® multi-cytokine assays, and a NOD/SCID mouse model of disseminated neuroblastoma. Results Co-culturing patient PBMC with aAPC for 14 days induced 2,363±443-fold expansion of CD56+CD3−CD14− NK cells with 83±4% purity (n=10). Results were similar with PBMC from normal donors (n=5). Expression of DNAM-1, NKG2D, FcγRIII/CD16 and CD56 increased 6±3, 10±2, 21±20, and 18±3-fold respectively on day 14 compared to day 0, demonstrating activation of NK cells. In vitro, aNK cells were highly cytotoxic against neuroblastoma cell lines, and killing was enhanced with GD2-specific monoclonal antibody ch14.18. When mediating cytotoxicity with ch14.18, release of TNFα, GM-CSF, IFNγ, sCD40L, CCL2/MCP-1, CXCL9/MIG, and CXCL11/I-TAC by aNK cells increased 4-, 5- 6-, 15-, 265-, 917- and 363-fold (151 to 9,121 pg/mL), respectively, compared to aNK cells alone. Survival of NOD/SCID mice bearing disseminated neuroblastoma improved when treated with thawed and immediately intravenously infused cryopreserved aNK cells compared to un-treated mice and was further improved when ch14.18 was added. Conclusion Propagation of large numbers of aNK cells that maintain potent anti-neuroblastoma activities when cryopreserved supports clinical testing of adoptive cell therapy with ch14.18.
Large-scale treatment of oily water arising from frequent marine oil spills presents a major challenge to scientists and engineers. Although the recently emerged phase-selective organogelators (PSOG) do offer very best promises for oil spill treatment, there still exists a number of technical barriers to overcome collectively, including gelators’ high solubility, high gelling ability, general applicability toward crude oil of various types, rapid gelation with room temperature operation, low toxicity, and low cost. Here, a denovo-designed unusually robust molecular gelling scaffold is used for facile construction of a PSOG library and for rapid identification of PSOGs with the most sought-after practical traits. The identified gelators concurrently overcome the existing technical hurdles, and for the first time enable instant room-temperature gelation of crude oil of various types in the presence of seawater. Remarkably, these excellent gelations were achieved with the use of only 0.058–0.18 L of environmentally benign carrier solvents and 7–35 g of gelator per liter of crude oil. Significantly, 2 out of 20 gelators could further congeal crude oil in the powder form at room temperature, highlighting another excellent potential of the developed modularly tunable system in searching for more powerful powder-based gelators for oil spill treatment.
A novel nanostructure of perpendicular ultrathin MoSe2 nanosheets directly grown on graphene was produced by a facile hydrothermal method in the presence of CTAB. The vertically-oriented and ultrathin MoSe2 nanosheets distribute uniformly on the surface of graphene, and the nanosheets are typically 2-3 layers, which is confirmed by TEM and red shift of the A1g Raman peak. In comparison with pure MoSe2 and MoSe2 nanospheres on graphene, vertically oriented MoSe2 nanosheets on graphene show enhanced organic dye adsorption ability and photocatalytic performance in the degradation of MB, RhB and MO under dark conditions and visible light irradiation. The excellent photocatalytic activity may be contributed by the unique perpendicular MoSe2 nanosheets with fully exposed active edges and hybridized with graphene for reduced electron-hole pair recombination.
On an industrial scale, the production of caminobutyric acid (GABA) from the cheaper sodium L-glutamate (L-MSG) is a valuable process. By entrapping Lactobacillus brevis cells with higher glutamate decarboxylase (GAD) activity into Ca-alginate gel beads, the biotransformation conditions of L-MSG to GABA were optimized with the immobilized cells. The cells obtained from a 60-h culture broth showed the highest biotransformation efficiency from L-MSG to GABA. The optimal cell density in gel beads, reaction pH and temperature were 11.2 g dry cell weight (DCW) l -1 , 4.4 and 40°C respectively. The thermal stability of immobilized cells was significantly higher than free cells. Under the optimized reaction conditions, the yield of GABA reached above 90% during the initial five batches and the yield still remained 56% in the tenth batch. Continuous production of GABA was realized with a higher yield by incorporating cell re-cultivation using the packed bed reactor.
OBJECTIVE: The aim of this study was to investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) in subjects who underwent a routine health checkup. We intended to establish a clinical association between NAFLD and MS as well as to compare the diagnostic criteria of MS based on the definitions set forth by the International Diabetes Federation (IDF), the US National Cholesterol Education Program Adult Treatment Panel III (2001) (NCEP/ATP‐III) and the Metabolic Syndrome Study Group of Chinese Diabetes Society (CDS). METHODS: Weight, height, waist circumference, hip circumference, percentage of body fat, blood pressure and ultrasound of liver were performed on subjects undergoing routine health checkup. Serum triglyceride, total cholesterol, high density lipoprotein cholesterol and fasting plasma glucose level were measured. RESULTS: A total of 2394 subjects were included in this analysis and 437 had NAFLD. The prevalence of MS in the whole sample according to IDF, NCEP/ATP‐III and CDS definitions was 11.11%, 8.48% and 5.30%, respectively. The total degree of agreement between IDF, NCEP/ATP‐III and CDS definition was 87.76%. The prevalence of MS in NAFLD subjects is much higher than that in non‐NAFLD subjects. The prevalence of NAFLD in MS subjects is also much higher than that in non‐MS subjects. CONCLUSION: The prevalence of MS varied depending on the diagnostic criteria used. NAFLD was strongly associated with the MS, although it remains unknown whether NAFLD is a cause or effect of MS.
Many ancestry informative SNP (AISNP) panels have been published. Ancestry resolution in them varies from three to eight continental clusters of populations depending on the panel used. However, none of these panels differentiates well among East Asian populations. To meet this need, we have developed a 74 AISNP panel after analyzing a much larger number of SNPs for Fst and allele frequency differences between two geographically close population groups within East Asia. The 74 AISNP panel can now distinguish at least 10 biogeographic groups of populations globally: Sub-Saharan Africa, North Africa, Europe, Southwest Asia, South Asia, North Asia, East Asia, Southeast Asia, Pacific and Americas. Compared with our previous 55-AISNP panel, Southeast Asia and North Asia are two newly assignable clusters. For individual ancestry assignment, the likelihood ratio and ancestry components were analyzed on a different set of 500 test individuals from 11 populations. All individuals from five of the test populations - Yoruba (YRI), European (CEU), Han Chinese in Henan (CHNH), Rondonian Surui (SUR) and Ticuna (TIC) - were assigned to their appropriate geographical regions unambiguously. For the other test populations, most of the individuals were assigned to their self-identified geographical regions with a certain degree of overlap with adjacent populations. These alternative ancestry components for each individual thus help give a clearer picture of the possible group origins of the individual. We have demonstrated that the new AISNP panel can achieve a deeper resolution of global ancestry.
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