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Many marine alkaloids possess interesting structures and antitumor activities. Thus, we have synthesized (2 E,4 E)-4-arylidene-2-styryl-5-oxopyrrolidine derivatives of the marine alkaloids, rhopaladins A–D. The cytotoxicities of these derivatives against C-33A, CaSki, SiHa, HeLa, HepG2, and LO2 cells are evaluated by MTT assays. The results show that (2 E,4 E)-2-(4-chlorostyryl)-4-benzylidene- N-cyclohexyl-1-(4-fluorophenyl)-5-oxopyrrolidine-2-carboxamide significantly inhibits cancer cell proliferation, with IC50 values against C-33A, CaSki, SiHa, HeLa, and HepG2 cells of 5.56, 9.15, 12.5, 21.4, and 14.5 μM, respectively, and an IC50 value of 86.77 μM against the normal LO2 cell line.

Herein, by introducing mismatches, a high-efficiency mismatch-fueled catalytic multiple-arm DNA junction assembly (M-CMDJA) with high-reactivity and a high-threshold is developed as a programmable DNA signal amplifier for rapid detection and ultrasensitive intracellular imaging of miRNA. Compared with traditional nucleic acid signal amplification (NASA) with a perfect complement, the M-CMDJA possesses larger kinetic and thermodynamic favorability owing to the more negative reaction standard free energy (Δ

A one-pot, base-mediated approach to Acanthus ilicifolius Linn alkaloid 2-benzoxazolinone derivatives is developed. Starting from trichloroacetic acid, o-aminophenol, substituted benzaldehydes and alkyl isocyanides, the desired 2-benzoxazolinone derivatives are obtained in good yields via a tandem Ugi condensation and intramolecular haloform cyclization at room temperature in the presence of Et3N.

A highly loaded and integrated core–brush three-dimensional (3D) DNA nanostructure is constructed by programmatically assembling a locked DNA walking arm (DA) and hairpin substrate (HS) into a repetitive array along a well-designed DNA track generated by rolling circle amplification (RCA) and is applied as a 3D DNA nanomachine for rapid and sensitive intracellular microRNA (miRNA) imaging and sensing. Impressively, the homogeneous distribution of the DA and HS at a ratio of 1 : 3 on the DNA track provides a specific walking range for the DA to avoid invalid and random self-walking and notably improve the executive ability of the core–brush 3D DNA nanomachine, which easily solves the major technical challenges of traditional Au-based 3D DNA nanomachines: low loading capacity and low executive efficiency. As a proof of concept, the interaction of miRNA with the 3D DNA nanomachine could initiate the autonomous and progressive operation of the DA to cleave the HS for ultrasensitive ECL detection of target miRNA-21 with a detection limit as low as 3.57 aM and rapid imaging in living cells within 15 min. Therefore, the proposed core–brush 3D DNA nanomachine could not only provide convincing evidence for sensitive detection and rapid visual imaging of biomarkers with tiny change, but also assist researchers in investigating the formation mechanism of tumors, improving their recovery rates and reducing correlative complications. This strategy might enrich the method to design a new generation of 3D DNA nanomachine and promote the development of clinical diagnosis, targeted therapy and prognosis monitoring., This study designed a highly loaded and integrated core–brush 3D DNA nanomachine for miRNA imaging and sensing, which easily solves the major technical challenges of traditional Au-based 3D nanomachines: low loading capacity and low executive efficiency.

Herein, we designed a dual 3D DNA nanomachine (DDNM)-mediated catalytic hairpin assembly (DDNM-CHA) to construct an electrochemical biosensor for ultrasensitive detection of miRNA, which possesses quite a faster reaction rate and much higher amplification efficiency than those of traditional catalytic hairpin assembly (CHA). Impressively, since the DDNM skillfully increases the local concentration of reactants and decreases the steric hindrance of substrates simultaneously, the DDNM-CHA could be endowed with higher collision efficiency and more effective reaction compared with traditional CHA, resulting in a hyper conversion efficiency up to 2.78 × 107 only in 25 min. This way, the developed DDNM-CHA could easily conquer the main predicaments: long reaction time and low efficiency. As a proof of the concept, we adopt the gold nanoparticles (AuNPs) and the magnetic nanoparticle (Fe3O4) as the kernel of DNM-A and DNM-B, respectively, and harness the magnetic electrode to directly adsorb the products H1-H2/Fe3O4 for constructing an immobilization-free biosensor for high-speed and ultrasensitive detection of miRNA with a detection limit of 0.14 fM. As a result, the DDNM-CHA we developed carves out a new insight to design a functional DNA nanomachine and evolve the analysis method for practical amplification in the sensing area and promotes the deeper exploration of the nucleic acid signal amplification strategy and DNA nanobiotechnology.

Herein, an efficient target-activated enzyme cascade electrocatalysis with low background signal was employed to establish electrochemical biosensor for ultrasensitive detection of thrombin via regulating electrocatalytic efficiency between target-induced hemin/G-quadruplex horseradish peroxidase-mimicking DNAzyme (HRP-mimicking DNAzyme) and glucose oxidase (GOx). Impressively, only when the target thrombin was introduced, the HRP-mimicking DNAzyme acting simultaneously as electrochemical signal probe would be formed to activate high-efficiency enzyme cascade electrocatalysis for reducing background signal significantly, which could overcome the defect of inevitable high background signal during the detection of target in the traditional cascade electrocatalysis of two existing bioenzymes. In addition, the detection sensitivity could be further improved by regulating the side length of rigid DNA tetrahedron (TDN) scaffold anchored HRP-mimicking DNAzyme and GOx at adjacent vertices for high enzyme cascade electrocatalytic efficiency. Consequently, the proposed biosensor demonstrated a low detection limit down to 0.3 fM for target thrombin, which provided a promising method for ultrasensitive monitoring of biomolecules in sensing analysis and disease diagnosis.

The signal transducers and activators of transcription 3 (STAT3) signaling pathway is a common feature in many solid tumors including non-small cell lung cancer, whereas current therapies usually fail to treat this disease in majority of cases. In the present study, we aimed to investigate the cytotoxic effect and the underlying mechanisms of SZC017, an oleanolic acid derivative, on human lung cancer cells. Cell viability was significantly decreased in SZC017-treated lung cancer cells. Mechanistically, SZC017 reduced A549 cell viability by activating both apoptosis and autophagy pathways. SZC017 was able to inhibit the phosphorylation of Akt, JAK2, and STAT3 in A549 cells, resulting in the inactivation of Akt and JAK2/STAT3 signaling pathways. In addition, SZC017 could induce ROS generation and Ca2+ release. Pretreatment with N-Acetyl L-Cysteine, a ROS scavenger, could fully reverse SZC017-induced ROS and increase the expression of Akt, p-STAT3, and procaspase-3, while decrease the ratio of LC3-II/I and the expression of Beclin-1. In summary, our study provides pharmacological evidence that SZC017 exhibits potential use in the treatment of lung cancer.

Oleanolic acid (OA) and its semi-synthetic derivatives have been reported to have a wide range of biological activities. The introduction of electrophilic Michael acceptor group can increase the reactivity of OA to cellular targets and thus improve the anti-tumor activity. In this work, a series of novel α,β-unsaturated carbonyl derivatives of OA were designed and synthesized. Their in vitro cytotoxic activity against MCF-7, HepG2 and HeLa cells were tested. Most derivatives exhibited improved cell growth inhibitory activity, especially for 3d with an IC50 of 0.77 μM in MCF-7 cells. Moreover, 3d inhibited the migration of MCF-7 and HeLa cells at the concentration of 4 μM. Flow cytometric analysis revealed that 3d induced cell apoptosis and S phase arrest in a concentration-dependent manner. Western blotting experiment demonstrated that 3d inhibited the phosphorylation of AKT and mTOR. These results suggest that this series of OA derivatives bearing exocyclic methylene ketone pharmacophore are promising anticancer agents as potential PI3K/AKT/mTOR pathway inhibitors.

With Raney nickel catalyst and aniline solvent, the reaction kinetics of catalytic hydrogenation of isophthalonitrile (IPN) for meta-xylenediamine (MXDA) preparation is studied in this paper. The experiment is conducted in a 1L büchiglas high-pressure hydrogenation reactor under the condition of the reaction temperature (100°C) and the reaction pressure (35 bar). The results shows that the kinetics equation proposed in this paper can be used to predict the response speed of IPN accurately.

Ethanolamine (EA, including MEA, DEA and TEA) is a kind of heat sensitive material. It is easy to be colored at high temperature which influences the product quality and its application. This paper studies the relationship between color number and time of MEA, DEA, TEA and their mixtures at different temperatures. The result shows that MEA is most sensitive to high temperature, TEA take the second place, DEA is almost unaffected. DEA can protect TEA and MEA from being colored, the more DEA content, the better effect. According to the results of tests and process simulation, optimized parameters of separation equipment and operation are put forward which can provide guidance for the production of high purity, low color number of TEA.

The solubility data of 2,4-dinitrotoluent (2,4-DNT) in mixed solvents of water and nitric acid with nitric acid mass fraction vary from 0.1 to 0.5 were determined at 283.15-323.15K by the equilibrium method. It indicates that the solubility increases with the increase of temperature and decreases with the decrease of mass fraction of nitric acid. The experimental data were correlated with λ-h equation, Apelblat equation and C.L.Yaws equation, average relative deviations of which between the calculated values and the experimental values of 25 data points in 5 systems were 3.666%, 2.737% and 3.121% respectively. The results show that three equations could well correlate the solubility data of 2,4-DNT in above electrolyte systems and the accuracy of the correlation can satisfy the engineering requirement.

Superconducting magnets using MgB2 tapes are potentially applicable in many areas, such as medical magnetic resonance imaging and fault current limiting. Under conduction cooling environments, the magnets can work at 15–20 K. In this work, a solenoid structured magnet with ∅ 100 mm bore is designed, built and tested. The maximum field at its center is up to 1.5 T. The field homogeneity, the thermal stability and the quench characteristics in the magnet are also investigated.

Embedded spilled oil recovery machine is one of the important mechanical equipment of oil spill emergency response and the speed synchronization of sweep arm end (float) and oil boom reel is the key technology of that. The problem of that line-speed synchronization of float and oil boom reel of embedded spilled oil recovery machine has been studied and the joint synchronization control scheme which adopt PID and equal control been also put forward in order to realize the speed coordination control of dual motor driven by HST with the PLC as the core of controller in this paper. The scheme of hardware design for the speed synchronization control system has been given and the software of the key technologies also been design and ran. The system speed has been simulated and analysis by MATLAB simulation software and the evaluation methods of the linear velocity errors been also put forward. Study in this paper provides reference for the follow-up projects and similar technical design. The stages of research results provide a reference for design work of the follow-up and similar technologies.

Although the intraluminal thread technique has been used to induce focal cerebral ischaemia in rabbits, its success rate is not high. We, therefore, attempted to improve the stability and reproducibility of this method by using thread tips of appropriate diameter as determined from the anatomical characteristics of the carotid and cerebral arteries of New Zealand white rabbits. Following intraarterial injection of casting material, we tested threads of four different tip diameters to determine the optimal thread tip that could occlude the middle cerebral artery (MCA). 2,3,5-Triphenyltertrazolium chloride (TTC) staining showed that, consistent with the intraluminal diameter of the MCA from the arterial casts ( 0.50 +/- 0.06 mm), thread with 0.51-0.55 mm tip diameter was optimal for the occlusion of the MCA. Ability to induce focal cerebral ischaemia was also dependent on variations in the anatomy of the internal carotid artery (ICA), especially the origin of the occipital artery. Our results suggest that use of appropriately sized thread and accurate manipulation of its tip significantly improves the stability and reproducibility of this model.

Scheduling for chemical batch process has been an active area of research over the past decade. The uncertainties of the process, which expand the scope and complexity, make the formulation and solution of the stochastic scheduling very intractable. A novel mathematical formulation which combined statistical probability theory with the deterministic scheduling was proposed. And the discretion of the stochastic variables transforms the stochastic programming problem into a probability statistics of deterministic scheduling, which overcomes the hardship. An example of stochastic scheduling of batch process with uncertain processing time of uniform distribution indicated that the relationship between the deadline and the probability of optimal scheduling, and the distribution of the makespan of the optimal scheduling with process time uncertainty was also studied. The proposed formation can also be used for the stochastic scheduling of batch process with uncertainty of market demand, equipment availability and so on.