Two homologous meroterpenoid gene clusters consisting of contiguous genes encoding polyketide synthase (PKS), prenyltransferase (PT), terpenoid cyclase (TC) and other tailoring enzymes were identified from two phylogenetically distinct fungi through computational analysis. Media optimization guided by reverse-transcription PCR (RT-PCR) enabled two strains to produce eight new and two known meroterpenoids (1-10). Using gene inactivation, heterologous expression, and biochemical analyses, we revealed a new polyketide-terpenoid assembly line that utilizes a pair of PKSs to synthesize 2,4-dihydroxy-6-alkylbenzoic acid, followed by oxidative decarboxylation, farnesyl transfer, and terpene cyclization to construct the meroterpenoid scaffold. In addition, two of the isolated meroterpenoids (3 and 17 d) showed immunosuppressive bioactivity. Our work reveals a new strategy for meroterpenoid natural products discovery, and reveals the biosynthetic pathway for compounds 1-10.

Aluminum-containing adjuvants have been used for nearly 100 years to enhance immune responses in billions of doses of vaccines. To date, only a few adjuvants have been approved for use in humans, among which aluminum-containing adjuvants are the only ones widely used. However, the medical need for potent and safe adjuvants is currently continuously increasing, especially those triggering cellular immune responses for cytotoxic T lymphocyte activation, which are urgently needed for the development of efficient virus and cancer vaccines. Manganese is an essential micronutrient required for diverse biological activities, but its functions in immunity remain undefined. We previously reported that Mn2+ is important in the host defense against cytosolic dsDNA by facilitating cGAS-STING activation and that Mn2+ alone directly activates cGAS independent of dsDNA, leading to an unconventional catalytic synthesis of 2′3′-cGAMP. Herein, we found that Mn2+ strongly promoted immune responses by facilitating antigen uptake, presentation, and germinal center formation via both cGAS-STING and NLRP3 activation. Accordingly, a colloidal manganese salt (Mn jelly, MnJ) was formulated to act not only as an immune potentiator but also as a delivery system to stimulate humoral and cellular immune responses, inducing antibody production and CD4+/CD8+ T-cell proliferation and activation by either intramuscular or intranasal immunization. When administered intranasally, MnJ also worked as a mucosal adjuvant, inducing high levels of secretory IgA. MnJ showed good adjuvant effects for all tested antigens, including T cell-dependent and T cell-independent antigens, such as bacterial capsular polysaccharides, thus indicating that it is a promising adjuvant candidate.

Genome mining targeting unique type II PKS and NRPS led to the identification of a novel class of glycopeptides named kitacinnamycins.

In China compared to the United States, donations are made by younger donors and donors give infrequently and make smaller WB donations. To help ensure supply adequacy, continued efforts are needed to have donors give larger volumes of WB in China.

The novel and well-defined supramolecular amphiphilic star-branched copolymer poly((caprolactone)-star-(poly(2-N,N-dimethylamino)ethylmethacrylate) 7 (PCL-(PDMAEMA) 7 ) with a porphyrin core was prepared via the combination of ring-opening polymerization (ROP), atom transfer radical polymerization (ATRP), and supramolecular host-guest inclusion complexation. After reaction of PDMAEMA with excess 1,3-propane sultone, the quaternized star-PCL-(PDMAEMA) 7 was obtained. The amphiphilic star-PCL-(PDMAEMA) 7 and quaternized star-PCL-(PDMAEMA) 7 can selfassemble into spherical nano-micelles by directly dissolving in water. This thermoresponsive micelles solution shows a transition from a lower critical solution temperature (LCST) of star-PCL-(PDMAEMA) 7 to an upper critical solution temperature (UCST) of quaternized star-PCL-(PDMAEMA) 7 , indicating that the LCST-UCST transition of micellar solutions can be accomplished by the transition of PDMAEMA to quaternized PDMAEMA. Due to the presence of porphyrin molecules in the micelles core, the micelle solutions present obvious fluorescence and the fluorescent intensity can be adjusted by altering the temperatures. For the star-PCL-(PDMAEMA) 7 micelle solution, the fluorescent intensity decreases with the increase of temperature, while the fluorescent intensity increases with the increase of temperature for the quaternized star-PCL-(PDMAEMA) 7 micelle solution, indicating unique temperature-fluorescence responsive behavior.

No abstract

The residual risk for transfusion-transmitted HCV infection is still relatively high in China. Incorporating NAT technology into blood donor screening would be estimated to reduce the residual risk of HCV infections eightfold over current EIA screening.

PurposeThe purpose of this study was to investigate the function of Zinc finger protein 488 (ZNF488) in nasopharyngeal carcinoma (NPC).Materials and MethodsThe endogenous expression of ZNF488 in NPC tissues, normal nasopharyngeal epithelium tissues and NPC cell lines were detected by quantitative reverse transcription polymerase chain reaction. ZNF488 over-expressing and knock-down NPC cell line models were established through retroviral vector pMSCV mediated over-expression and small interfering RNA (siRNA) mediated knock-down. The invasion and migration capacities were evaluated by wound healing and transwell invasion assays in ZNF488 over-expressing and control cell lines. Soft-agar colony formation and a xenograft experiment were performed to study tumorigenic ability in vitro and in vivo. Immunofluorescence and western blotting analysis were used to examine protein changes followed by ZNF488 over-expression. Microarray analysis was performed to explore gene expression profilings, while luciferase reporter assay to evaluate the transcriptive activity of Tcf/Lef.ResultsZNF488 was over-expressed in NPC tissues compared with normal tissues, especially higher in 5-8F and S18, which are well-established high metastatic NPC clones. Functional studies indicate that over-expression of ZNF488 provokes invasion, whereas knock-down of ZNF488 alleviates invasive capability. Moreover, over-expression of ZNF488 promotes NPC tumor growth both in vitro and in vivo. Our data further show that over-expression of ZNF488 induces epithelial mesenchymal transition (EMT) by activating the WNT/β-catenin signaling pathway.ConclusionOur data strongly suggest that ZNF488 acts as an oncogene, promoting invasion and tumorigenesis by activating the Wnt/β-catenin pathway to induce EMT in NPC.