Surmounting tumor resistance to metallodrugs by co-loading a metal complex and siRNA in nanoparticles

Copper complexes are promising anticancer agents widely studied to overcome tumor resistance to metal-based anticancer drugs. Nevertheless, copper complexes per se encounter drug resistance from time to time. Adenosine-5′-triphosphate (ATP)-responsive nanoparticles containing a copper complex CTND and B-cell lymphoma 2 (Bcl-2) small interfering RNA (siRNA) were constructed to cope with the resistance of cancer cells to the complex. CTND and siRNA can be released from the nanoparticles in cancer cells upon reacting with intracellular ATP. The resistance of B16F10 melanoma cells to CTND was terminated by silencing the cellular Bcl-2 gene via RNA interference, and the therapeutic efficacy was significantly enhanced. The nanoparticles triggered a cellular autophagy that amplified the apoptotic signals, thus revealing a novel mechanism for antagonizing the resistance of copper complexes. In view of the extensive association of Bcl-2 protein with cancer resistance to chemotherapeutics, this strategy may be universally applicable for overcoming the ubiquitous drug resistance to metallodrugs.

Bcl-2-related tumor resistance to anticancer drugs can be overcome by silencing the cellular Bcl-2 gene via RNA interference. The realization of the goal is exemplified by delivering Bcl-2 siRNA and a tumor-resistant Cu complex to cancer cells with an ATP-responsive nanocarrier.     

Synthesis of （2R,4R）—2—N—tert—Butyloxycarbonyl Amino—4,5—epoxido—valeric Acid Methyl Ester

The stereoselective synthesis of (2R,4R)-2-N-tert-butyloxycarbonyl amino-4,5-epoxido-valeric acid methyl ester 8,which is the key intermediate for the synthesis of (2′S,2R)-3-trans-nitrocyclopropyl-alanine,was first accomplished.     

无机盐对正负表面活性剂混合体系性质的影响

用滴体积法测定了四种离子强度下(μ=0.02, 0.05, 0.1, 0.2 mol·kg~(-1), 支持电解质为NaBr)C_(12)H_(25)SO_4Na/C_6H_(13)(NC_5H_5)Br混合体系在五种比例(10:1, 3:1, 1:1, 1:3, 1:10)时的临界胶团活度cma(25 ℃). 提出了无机盐对正负表面活性剂混合体系临界胶团活度的影响程度的计算式.     

Chemiluminescence detection coupled to high-performance frontal analysis for the determination of unbound concentrations of drugs in protein binding equilibrium

High-performance frontal analysis coupled with chemiluminescence detection (HPFA-CL) was developed for the determination of unbound oxacillin concentration in human serum albumin solution. The HPFA system consisted of an ISRP column and a mobile phase of 67 mM potassium phosphate buffer of pH 7.4 and ionic strength of 0.17. The luminol-H2O2-Co2+ system was used in the chemiluminescence detection. An enhancement of luminol chemiluminescence by oxacillin was investigated and employed for determining the concentration of oxacillin in the HPFA eluate. Sample solutions were directly injected onto the column; the drug was eluted as a zonal peak with a plateau region. The unbound drug concentrations were determined by using the height of the plateau. The results agreed with those obtained with conventional ultrafiltration-HPLC method. Good reproducibility was confirmed by the within run and between run RSD < or = 7.4%. HPFA-CL provided a selective method for determination of unbound drug concentration in protein binding equilibrium.     

A general approach to cyathin diterpenes. Total synthesis of allocyathin B(3)

[reaction: see text] The synthesis of allocyathin B(3) from an advanced intermediate possessing the ring system and relative stereochemistry but lacking the isopropyl and hydroxymethyl groups is reported. The isopropyl group was introduced by radical cyclization of a methyl propargyl acetal of an alpha-bromo ketone, and the hydroxymethyl group was generated by Pd-catalyzed carbonylation of a vinyl triflate. The route provides functionalized intermediates that could allow access to more complex members of the cyathin family of diterpenes.     

Diffusion exchange NMR spectroscopic study of dextran exchange through polyelectrolyte multilayer capsules

Diffusion exchange of dextran with molecular weights 4.4 and 77 kDa through polyelectrolyte multilayer (PEM) hollow capsules consisting of four bilayers of polystyrene sulfonate/polydiallyldimethylammonium chloride has been investigated using two-dimensional nuclear-magnetic-resonance methods: diffusion-diffusion exchange spectroscopy (DEXSY) and diffusion-relaxation correlation spectroscopy (DRCOSY). Results obtained in DRCOSY experiments show that the diffusion process of dextran 77 kDa exhibits an observation time dependence suggesting a diffusion behavior restricted by confinement. We find evidence for both single capsule and capsule aggregate states, with a partitioning of the 77-kDa dextran between the free and capsule states much larger than that suggested by volume fraction alone. Results from DEXSY experiments show that dextran 77 kDa is in diffusive exchange through the capsules with an exchange time of around 1 s. In contrast, the capsules have no detectable influence on the diffusion process of the dextran 4.4 kDa. This quantitative information may be used in designing PEM capsules as drug carriers.     

The growth of perylene on Ru(0001)

The structure of perylene adsorbed on Ru(0001) surface has been studied by ultraviolet photoemission spectroscopy (UPS) and low-energy electron diffraction. An ordered p(4x4) structure is observed from a monolayer (about 4 A thickness) of the perylene on Ru(0001) surface. UPS measurements show the molecular features, from the perylene multiplayer, between 2 and 10 eV below the Fermi level. Angle-resolved ultraviolet photoemission spectroscopy measurements suggest that the perylene molecular plane is parallel to the substrate. Temperature dependent UPS measurements show that the perylene multilayer is stable on Ru(0001) surface up to 125 degrees C. The desorption of the multilayer and the decomposition of the monolayer are observed above 125 degrees C.     

Small World Effects in a Harmonious Unifying Hybrid Preferential Model Networks

Small world effects in the harmonious unifying hybrid preferential model (HUHPM) networks are studied both numerically and analytically. The idea and method of the HUHPM is applied to three typical examples of unweighted BA model, weighted BBV model, and the TDE model, so-called HUHPM-BA, HUHPM-BBV and HUHPM-TDE networks. Comparing the HUHPM with current typical models above, it is found that the HUHPM networks has the smallest average path length and the biggest average clustering coefficient. The results demonstrate that the HUHPM is more suitable not only for the un-weighted models but also for the weighted models.     

Characterization of Roasting Time on Sensory Quality,Color, Taste,and Nonvolatile Compounds of Yuan An Yellow Tea

Roasting is crucial for producing Yuan An yellow tea (YAYT) as it substantially affects sensory quality. However, the effect of roasting time on YAYT flavor quality is not clear. To investigate the effect of roasting time on the sensory qualities, chemical components, odor profiles, and metabolic profile of YAYTs produced with 13 min roasting, 16 min roasting, 19 min roasting, 22 min roasting, and 25 min roasting were determined. The YAYTs roasted for 22 min got higher sensory scores and better chemical qualities, such as the content of gallocatechin (GC), gallocatechin gallate (GCG), free amino acids, solutable sugar, meanwhile the lightness decreased, the hue of tea brew color (b) increased, which meant the tea brew got darker and yellower. YAYTs roasted for 22 min also increased the contents of key odorants, such as benzaldehyde, nonanal, β-cyclocitral, linalool, nerol, α-cedrol, β-ionone, limonene, 2-methylfuran, indole, and longiborneol. Moreover, non-targeted metabolomics identified up to 14 differentially expressed metabolites through pair-wise comparisons, such as flavonoids, phenolic acids, sucrose, and critical metabolites, which were the main components corresponding to YAYT roasted for 22 min. In summary, the current results provide scientific guidance for the production of high quality YAYT.