Latest ArticlesNuclear RNA export into the cytoplasm is one of the key steps in protein expression to realize biological functions. Despite the broad availability of nucleic acid dyes, tracking and quantifying the highly dynamic process of RNA export in live cells is challenging. When dye-labeled RNA enters the cytoplasm, the dye molecules are released upon degradation of the RNA, allowing them to re-enter the cell nucleus. As a result, the ratio between the dye exported with RNA into the cytoplasm and the portion staying inside the nucleus cannot be determined. To address this common limitation, we report the design of a smart probe that can only check into the nucleus once. When adding to cells, this probe rapidly binds with nuclear RNAs in live cells and reacts with intrinsic H2S. This reaction not only activates the fluorescence for RNA tracking but also changes the structure of probe and consequently its intracellular localization. After disassociating from exported RNAs in cytoplasm, the probe preferentially enters lysosomes rather than cell nucleus, enabling real-time quantitative measurement of nuclear RNA exports. Using this probe, we successfully evaluated the effects of hormones and cancer drugs on nuclear RNA export in live cells. Interestingly, we found that hormones inhibiting RNA exports can partially offset the effect of chemotherapy.
Hollow fiber microfiltration (MF) and ultrafiltration (UF) membrane processes have been extensively used in water purification and biotechnology. However, complicated filtration hydrodynamics wield a negative influence on fouling mitigation and stability of hollow fiber MF/UF membrane processes. Thus, establishing a mathematical model to understand the membrane processes is essential to guide the optimization of module configurations and to alleviate membrane fouling. Here, we present a comprehensive overview of the hollow fiber MF/UF membrane filtration models developed from different theories. The existing models primarily focus on membrane fouling but rarely on the interactions between the membrane fouling and local filtration hydrodynamics. Therefore, more simplified conceptual models and integrated reduced models need to be built to represent the real filtration behaviors of hollow fiber membranes. Future analyses considering practical requirements including complicated local hydrodynamics and nonuniform membrane properties are suggested to meet the accurate prediction of membrane filtration performance in practical application. This review will inspire the development of high-efficiency hollow fiber membrane modules.
With an intensive understanding of the mechanism of immune system, developing a therapeutic tumor vaccine is one of the most perspective strategy of cancer immunotherapy. In this study, we report a facile approach to prepare graphene oxide (GO)-based therapeutic cancer-nanovaccine. The model antigen (ovalbumin, OVA) and adjuvant (CpG ODN), are conjugated with GO-PEI nanosheet through electrostatic interaction. The addition of PEG can improve biocompatibility and prevent nanoparticle aggregation. The prepared GO-based nanovaccine, GO-PEI-OVA-PEG-CpG, exhibits good biocompatibility and low toxicity both in vivo and in vitro. More importantly, it can efficiently induce the maturation of dendritic cells (DCs), the enhancement of antigen cross-presentation ability, and the amplification of cytokine production of immune cells. Impressively, this nanovaccine shows a remarkable therapeutic effect against pre-established B16-OVA-melanoma tumors, which can significantly inhibit tumor growth and prolong the survival time of the OVA-expressed tumor-bearing mice. Moreover, combining GO-PEI-OVA-PEG-CpG with NLG919, an IDO-1 (indoleamine-2,3-dioxygenase) inhibitor which can regulate the tumor microenvironment, displays a synergistic therapeutic effect. These findings indicate the GO-PEI-OVA-PEG-CpG nanovaccine actively induces an antigen-specific antitumor immune response and it combined with NLG919 could achieve better therapeutic outcomes.
A series of pyrazolone derivatives bearing a tetrasubstituted chiral center were prepared by virtue of a Lewis acid-catalyzed Friedel-Crafts reaction, in which a chiral copper complex was employed as the catalyst. This reaction can be carried out smoothly under mild condition to afford the pyrazolone derivatives with high yields (up to 85%) and excellent enantioselectivities (up to 99%). In addition, the gram scale synthesis proved the practicality of this reaction.
To obtain high-efficiency flame retardancy of epoxy resins, a cyclophosphazene derivative tri-(o-henylenediamino)cyclotriphosphazene (3ACP) was successfully synthesized and used as a curing agent for the thermosetting of an epoxy resin system. The flame retardant properties, thermal stability, and pyrolysis mechanism of the resultant thermosets were investigated in detail. The experiments indicated that the synthesized thermoset achieved a UL-94 V-0 rate under a vertical burning test as well as a limiting oxygen index (LOI) of 29.2%, which was able to reach V-0 even when a small amount of 3ACP was incorporated. Scanning electronic microscopic observation demonstrated that the char residue of the thermosets was extremely expanded after the vertical flame test. Thermal analysis showed that the samples had a lower initial decomposition temperature when 3ACP was introduced into the epoxy resin systems. This indicates that the carbonization ability of the thermosets was significantly improved at elevated temperatures. In addition, the incorporation of 3ACP can effectively suppress the release of combustible gases during the pyrolysis process, and the decomposition of E-44/DDS-3ACP curing systems also promotes the formation of polyphosphoramides charred layer in the condensed phase. The investigation on the chemical structures of both the gaseous and condensed phase pyrolysis process confirmed the flame-retardant mechanism of the 3ACP-cured epoxy resins. Therefore, the nonflammable halogen-free epoxy resin developed in this study has potential applications in electric and electronic fields for environment protection and human health.
Sugar-dependent targeting and immune adjuvant effects of hyperbranched glycosylated polypeptide nanoparticles were disclosed for ovalbumin (OVA) delivery system. The mannose-coated polypeptide nanoparticles can induce strongest targeting and immune adjuvant effects to macrophages than those glucose/lactose-coated ones, which effectively transported OVA into cells and facilitated OVA subcellular escape from endolysosomes into cytoplasm with the assistance of UV irradiation or intracellular acidic pH.
Herein, we report a practical electro-reductive protocol for the direct C–H cyanoalkylation of quinoxalin-2(1H)-ones via iminyl radical-mediated ring opening. These mild reactions proceed under metal-, reductant-, and reagent-free conditions to provide synthetically useful cyanoalkylated quinoxalin-2(1H)-ones.
Aflatoxin B1 (AFB1) is one of the most common mycotoxins that threatens human health. As single-stranded oligonucleotides with high affinity and specificity, aptamers have incomparable effect on the targeted detection of AFB1. Herein, after 11 rounds of selection and analysis using a modified affinity chromatography-based SELEX strategy, the truncated 37 nt aptamer AF11–2 was successfully obtained. The aptamer shows good detection performance for AFB1, and can sensitively detect AFB1 in the range of 100–1000 nmol/L, with a detection limit of 42 nmol/L. In the detection of pretreated edible peanut oil samples, AF11–2 aptamer also showed a high recovery rate and good stability for AFB1, and achieved satisfactory results. In addition, AF11–2 aptamer can significantly enhance the fluorescence ability of AFB1, which is not available in traditional Afla17–2–3 aptamer. After molecular docking analysis, it was found that AF11–2 and Afla17–2–3 had different nucleotide binding sites for AFB1. Afla17–2–3 binds to the carbonyl O of AFB1, while AF11–2 binds to the pyrrolic O of AFB1, which may be the main reason that AF11–2 can enhance the fluorescence of AFB1.
We report a Ni-catalyzed three-component cross-electrophile coupling of alkynes with alkenyl halides and fluoroalkyl halides to generate fluoroalkyl-incorporated 1,3-dienes. This mild and operationally simple protocol is distinguished by its broad substrate scope and excellent chemo-, regio-, and stereo-selectivity, offering a new and organometallic agent-free platform for the construction of fluoroalkyl-incorporated diene motifs. Preliminary mechanistic studies have been conducted to probe the potential reaction pathway.
A Ru(Ⅲ)-catalyzed annulation reaction of 2-aminoaromatic aldehydes (ketones) and isoxazoles to afford diverse 3-cyanoquinolines has been developed. Notably, isoxazole acted as a cyclization reagent and nontoxic cyano source via N-O bond cleavage and fragmentation. Variously substituted (especially 6- or 7-substituted) quinolines could be easily afforded. This procedure features wide functional group compatibility, efficiency and avoiding toxic cyano source. Meanwhile, this protocol could be successfully applied to scale-up synthesis. Further chemical transformations of 3-cyanoquinoline could give some valuable skeletons, demonstrating its potential in synthetic application
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