Quantitatively delineating the activation network of multiple proteases that participate in cellular processes is highly essential for understanding the physiological and pathological states of cells. In this study, protease-responsive mass barcoded nanotranslators (PRMNTs) were engineered for revealing the activity of cascaded caspases in apoptosis in a multiplex and quantitative manner. In the PRMNTs, a series of mass tag-decorated gold nanoparticles (AuNPs) were tethered onto magnetic Fe3O4 nanospheres via a linker containing the substrate peptide of the target protease to form a “one-to-many” core–satellite structure. This nanostructure was internalized into the cells, underwent an enzymatic reaction within the cells, and allowed post-reaction mass spectrometry (MS) interrogation after magnetic separation from the cells. In the presence of intracellular caspases, enzymatic cleavage of the linker could be translated to the decreased ion signals of the mass tags on the remaining AuNPs in the PRMNTs by MS decoding. Benefiting from the multiplexing capability of MS, the intracellular activity of caspase-3, -8 and -9 that orchestrate the apoptotic process was simultaneously quantified at any given time. Kinetic analysis of caspase activity under stimulation of diverse anticancer drugs revealed that programmed cell death followed individual apoptosis pathways, differing in the activation degree and sequence of the caspase cascade. This work represents a modality that interfaces nanotechnology with MS for quantitatively probing the intracellular activity of multiple proteases, which opens up new avenues for revealing the apoptosis mechanism and developing innovative drugs.Protease-responsive mass barcoded nanotranslators (PRMNTs) were engineered for revealing the apoptosis pathways by MS-based multiplex quantification of the intracellular activity of cascaded caspases.相似文献
New silica-based europium fluorescent nanoparticles having surface amino groups were prepared by a covalent binding-copolymerization technique. In the nanoparticles, the fluorescent Eu3+ chelate molecules were covalently bound to silicon atoms to protect the nanoparticles from dye leaking in bio-applications. The amino groups on the surface of nanoparticles made the surface modification and bioconjugation of nanoparticles easier. The nanoparticles were characterized and developed as a new type of fluorescence probe for a highly sensitive time-resolved fluoroimmunoassay (TR-FIA) of human hepatitis B surface antigen (HBsAg). 相似文献
A recyclable Ruthenium tris [4,4′-bis (dinonylmethyl)-2,2′-bipyridine] (Ru[(DNM)2bpy]32+) photocatalyst (PC) was synthesized. Hexane-phase-selective solubility allowed its simple and efficient separation from reaction products via solvent extraction. The excellent catalytic activity and recoverability were demonstrated in batch and flow perfluoroalkylation reactions of coumarin under visible-light irradiation. High reaction rates and easy reusability of the catalyst make this approach attractive for large-scale applications. 相似文献
Medicines or drugs have unique characteristics of short life cycle, small size, light weight, restrictive distribution time and the need of temperature and humidity control (selected items only). Thus, logistics companies often use different types of vehicles with different carrying capacities, and considering fixed and variable costs in service delivery, which make the vehicle assignment and route optimization more complicated. In this study, we formulate the problem to a multi-type vehicle assignment and mixed integer programming route optimization model with fixed fleet size under the constraints of distribution time and carrying capacity. Given non-deterministic polynomial hard and optimal algorithm can only be used to solve small-size problem, a hybrid particle swarm intelligence (PSI) heuristic approach, which adopts the crossover and mutation operators from genetic algorithm and 2-opt local search strategy, is proposed to solve the problem. We also adapt a principle based on cost network and Dijkstra’s algorithm for vehicle scheduling to balance the distribution time limit and the high loading rate. We verify the relative performance of the proposed method against several known optimal or heuristic solutions using a standard data set for heterogeneous fleet vehicle routing problem. Additionally, we compare the relative performance of our proposed Hybrid PSI algorithm with two intelligent-based algorithms, Hybrid Population Heuristic algorithm and Improved Genetic Algorithm, using a real-world data set to illustrate the practical and validity of the model and algorithm.
A series of three-dimensional (3D) novel coordination polymers M(bpdc)1.5(H2O) x 0.5DMF (M = Tb (1), Ho (2), Er (3), or Y (4)) have been synthesized by reaction of the rare earth ions (M3+) with 4,4'-biphenyldicarboxylic acid (H2bpdc) in a mixed solution of DMF and C2H5OH. They possess the same 3D architectures and crystallize in monoclinic space group C2/c. Two seven-coordinated metal centers and four dimonodentate bpdc groups construct a paddle-wheel building block. These building blocks connect with two carboxyl groups to lead to a one-dimensional inorganic chain, ---M-O-C-O-M---, along the [001] direction. The inorganic chains are linked with two biphenyl groups to form 25.15 A x 17.09 A rhombic channels along the c axis without interpenetration. These complexes exhibit strong fluorescence in the visible region, and complex 3 shows Er3+ characteristic emission in the range of 1450-1650 nm at room temperature. These complexes could be anticipated as potential fluorescent probes and an IR-emitter, respectively. 相似文献
In this study, a fluorine-containing flow modifier (Si-DF) with low surface energy is successfully synthesized, which is applied to fabricate ideal electronic packaging materials (BN/PPS composites) with high thermal conductivity, excellent dielectric properties, processability, and toughness by conventional melt blending. Si-DPF is located at the interface between the BN fillers and the PPS matrix, which not only improves the dispersion of BN fillers but also strengthens the interaction. With the help of 5 wt% Si-DF, BN/PPS/Si-DF (70/25/5) still exhibits the high thermally conductive coefficient (3.985 W/m·K) and low dielectric constant (3.76 at 100 MHz) although BN fillers are loaded as high as 70 wt%. Moreover, the sample processes a lower stable torque value (2.5 N·m), and the area under the stress–strain curves is also increased. This work provides an efficient way to develop high-performance polymer-based composites with high thermally conductive coefficients and low dielectric constants for electronic packaging applications. 相似文献