Nanoscale Organization of TRAIL Trimers using DNA Origami to Promote Clustering of Death Receptor and Cancer Cell Apoptosis.

Through inducing death receptor (DR) clustering to activate downstream signaling, tumor necrosis factor related apoptosis inducing ligand (TRAIL) trimers trigger apoptosis of tumor cells. However, the poor agonistic activity of current TRAIL-based therapeutics limits their antitumor efficiency. The nanoscale spatial organization of TRAIL trimers at different interligand distances is still challenging, which is essential for the understanding of interaction pattern between TRAIL and DR. In this study, a flat rectangular DNA origami is employed as display scaffold, and an "engraving-printing" strategy is developed to rapidly decorate three TRAIL monomers onto its surface to form DNA-TRAIL3 trimer (DNA origami with surface decoration of three TRAIL monomers). With the spatial addressability of DNA origami, the interligand distances are precisely controlled from 15 to 60 nm. Through comparing the receptor affinity, agonistic activity and cytotoxicity of these DNA-TRAIL3 trimers, it is found that ≈40 nm is the critical interligand distance of DNA-TRAIL3 trimers to induce death receptor clustering and the resulting apoptosis.Finally, a hypothetical "active unit" model is proposed for the DR5 clustering induced by DNA-TRAIL3 trimers.

Fingerprint combining with quantitative analysis of multi-components by single marker for quality control of Chenxiang Huaqi tablets.

BACKGROUND: Chenxiang Huaqi tablets (CXHQTs) are a traditional Chinese medicine (TCM) commonly used to treat stomach-related diseases. Currently, the ministerial standards do not provide detailed guidance and regulations on the content determination of CXHQTs, and the reported studies only use individual active components as indicators for determining effective ingredients. OBJECTIVE: The present study aimed to propose a methodology for quality control of CXHQTs based on high-performance liquid chromatography (HPLC) fingerprinting combined with the quantitative analysis of multi-components by single marker (QAMS) method. METHODS: HPLC method was used to determine seven active ingredients and performed fingerprint analysis of CXHQTs. To further process chemometric assessment, technical analysis-model including similarity analysis (SA), hierarchical clustering analysis (HCA), principal components analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA) was set up to differentiate and classify the 20 batches of samples. RESULTS: After comparing the results of QAMS method with the external standard method (ESM), we found there is no significant difference. Besides, the fingerprint of CXHQT was also established. CONCLUSION: HPLC fingerprint combined with the QAMS could be an efficient and selective analysis technique to achieve a qualitative and quantitative evaluation of executing quality processes.

Comprehensive Quality Evaluation of Qizhi Xiangfu Pills Based on Quantitative Analysis of Multi-Components by a Single Marker Combined with GC Fingerprints and Chemometrics.

BACKGROUND: Qizhi Xiangfu Pills (QXPs) are a traditional Chinese medicine (TCM) used clinically for qi stagnation and blood stasis. The current quality control of QXPs in the ministry standards and the reported literature is minimal, and requires improvement. OBJECTIVE: This study aimed to analyze and determine the active ingredients in QXPs for its overall evaluation. METHODS: In this study, a quantitative analysis of multi-components by a single marker (QAMS) method was established to simultaneously determine caryophyllene oxide, cyperotundone, ligustilide, and α-cyperone in QXPs by GC. Moreover, the GC fingerprints of 22 batches of samples were also established, and the common peaks were initially identified by GC-MS, then classified in various dimensions using chemometric methods, and the main markers causing the discrepancies between groups were analyzed by orthogonal partial least-squares discrimination analysis (OPLS-DA). RESULTS: Compared with an internal standard method (ISM), the determination results obtained by QAMS had no significant difference. Twenty-two common peaks were distinguished in the fingerprint of 22 batches of QXPs, 17 of which were identified, and the similarity of the fingerprints was greater than 0.898. The 22 batches of QXPs were roughly divided into 3 categories, and 12 main markers causing the discrepancies were discovered. CONCLUSION: The established QAMS method combined with the GC fingerprint and chemometrics is convenient and feasible, which helps to improve the quality evaluation of QXPs and provides a demonstration for the related study of compound preparations and single herbs. HIGHLIGHTS: QAMS combined with a GC fingerprint and chemometrics method was established to evaluate the quality of QXPs for the first time.

Fluorous-Directed Assembly of DNA Origami Nanostructures.

An orthogonal, noncovalent approach to direct the assembly of higher-order DNA origami nanostructures is described. By incorporating perfluorinated tags into the edges of DNA origami tiles we control their hierarchical assembly via fluorous-directed recognition. When we combine this approach with Watson-Crick base-pairing we form discrete dimeric constructs in significantly higher yield (8x) than when either molecular recognition method is used in isolation. This integrated "catch-and-latch" approach, which combines the strength and mobility of the fluorous effect with the specificity of base-pairing, provides an additional toolset for DNA nanotechnology, one that enables increased assembly efficiency while requiring significantly fewer DNA sequences. As a result, our integration of fluorous-directed assembly into origami systems represents a cheap, atom-efficient means to produce discrete superstructures.

Degradation of Dynamic Elastic Modulus of Concrete under Periodic Temperature-Humidity Action.

Cracks caused by environmental temperature and humidity variation are generally considered one of the most important factors causing durability deterioration of concrete structures. The seasonal or daily variation of ambient temperature and humidity can be considered periodic. The dynamic modulus of elasticity is an important parameter used to evaluate the performance of structural concrete under periodic loads. Hence, in this paper, the dynamic elastic modulus test of concrete under simulating periodic temperature-humidity variation is carried out according to monthly meteorological data of representative areas (Nanjing, China). The dynamic elastic modulus attenuation pattern and a dynamic elastic modulus degradation model of concrete under periodic temperature-humidity are investigated. The test results show that the dynamic elastic modulus of concrete decreases and tends to be stable under the action of periodic temperature-humidity. Comparative analysis shows that the two-parameter dynamic elastic modulus degradation model is more suitable for describing the dynamic elastic modulus attenuation pattern of concrete under periodic temperature-humidity action than the single-parameter one.

Transformation of external sulphate and its effect on phosphorus mobilization in Lake Moshui, Wuhan, China.

Average concentrations of sulphate in lakes continue to increase sharply. The response of phosphorus to sulphate input is of great importance due to the relationship between eutrophication and ecological health. A four-week experiment was conducted under simulated conditions using samples from a heavily polluted lake, Lake Moshui, in Wuhan, China, to examine the influence of external sulphate on phosphorus release and the transformation of sulphate. The results showed that the diffusion of sulphate into the sediments promoted the proliferation of sulphate-reducing bacteria (SRB) and the reduction of sulphate. Acetic acid was consumed due to sulphate reduction. The soluble reactive phosphorus (SRP) and soluble Fe measured with diffusive equilibration in thin-films (DET) probes increased significantly after the input of sulphate. The content of SRP was consistent with the variation in both the SRB number and the S(0) content in the sediments. The maximum SRP concentration of 100.43 mg L(-1) was recorded 3 cm below the sediment-water interface on the 29th d, which was more than twice the value of the control. There was a positive correlation between concentrations of Fe and SRP in the overlying water and the pore water of the sediments.