Enhanced Aggregation-Induced Delayed Electrochemiluminescence Triggered by Spatial Perturbation of Organic Dots.

Development of highly efficient, heavy-metal-free electrochemiluminescence (ECL) materials is attractive but still challenging. Herein, we report an aggregation-induced delayed ECL (AIDECL) active organic dot (OD) composed of a tert-butoxy-group-substituted benzophenone-dimethylacridine compound, which shows high ECL efficiency. The resultant ODs exhibit 2.1-fold higher ECL efficiency compared to control AIDECL-active ODs. Molecular stacking combined with theoretical calculations suggests that tert-butoxy groups effectively participate in the intermolecular interactions, further inhibiting the molecular motions in the aggregated states and thus accelerating radiative decay. On the basis of these ODs exhibiting excellent ECL performance, a proof-of-concept biosensor is constructed for the detection of miR-16 associated with Alzheimer's disease, which demonstrates excellent detection ability with the limit of detection of 1.7 fM. This work provides a new approach to improve the ECL efficiency and enriches the fundamental understanding of the structure-property relationship.

Retracted: The Effects of Ludartin on Cell Proliferation, Cell Migration, Cell Cycle Arrest and Apoptosis Are Associated with Upregulation of p21WAF1 in Saos-2 Osteosarcoma Cells In Vitro.

The authors repeated experiments and found that the results shown in figure 2 were not reproducible. Reference: Shuang-li Zhang, Bao-lin Li, Wei Li, Ming Lu, Lin-ying Ni, Hui-li Ma, Qing-gang Meng. The Effects of Ludartin on Cell Proliferation, Cell Migration, Cell Cycle Arrest and Apoptosis Are Associated with Upregulation of p21WAF1 in Saos-2 Osteosarcoma Cells In Vitro. Med Sci Monit 2018; 24: LBR4926-4933. 10.12659/MSM.909193.

The Effects of Ludartin on Cell Proliferation, Cell Migration, Cell Cycle Arrest and Apoptosis Are Associated with Upregulation of p21WAF1 in Saos-2 Osteosarcoma Cells In Vitro.

BACKGROUND The aim of this study was investigate the effects of the sesquiterpene lactone, ludartin, on cell proliferation, cell migration, apoptosis, and the cell cycle in osteosarcoma cell lines, compared with a normal osteoblast cell line. MATERIAL AND METHODS Osteosarcoma cell lines, MG-63 Saos-2 U-2OS, T1-73 143B, and HOS, and normal hFOB 1.19 osteoblasts, were cultured and treated with increasing doses of ludartin, The MTT colorimetric assay was used to measure cell metabolic activity and viability. Apoptosis was studied by fluorescence-activated cell sorting (FACS) using 4',6-diamidino-2-phenylindole (DAPI) nuclear staining and Annexin-V/propidium iodide (PI) staining. Cell cycle was studied using flow cytometry. Cell migration and invasion were studied using wound healing and Boyden chamber assays. Protein expression was measured by Western blotting. RESULTS Ludartin inhibited cell viability, cell migration, cell proliferation, and increased cell apoptosis, in all osteosarcoma cell lines, with an IC50 dose ranging from 15-30 µM. The greatest effects were on the Saso-2 osteosarcoma cells, with an IC50 of 15 µM. However, ludartin showed minor cytotoxic effects of the normal hFOB 1.19 osteoblasts (IC50 >100 µM). Ludartin exerted its anti-proliferative effects on Saos-2 cells via induction of apoptosis and cell cycle arrest at the G2/M checkpoint, associated with reduced expression of Cdc25c (Ser216), Cdc25c, pCdc2 (Tyr15), and Cdc2 and increased expression of p21WAF1. Ludartin inhibited cell migration and invasion of the Saos-2 cells. CONCLUSIONS The dose-dependent effects of ludartin on cell proliferation, migration, apoptosis, cell cycle arrest at the G2/M checkpoint involved p21WAFI in Saos-2 osteosarcoma cells.

Multicellular tumor spheroids as an in vivo-like tumor model for three-dimensional imaging of chemotherapeutic and nano material cellular penetration.

We present a flexible and highly reproducible method using three-dimensional (3D) multicellular tumor spheroids to quantify chemotherapeutic and nanoparticle penetration properties in vitro. We generated HeLa cell-derived spheroids using the liquid overlay method. To properly characterize HeLa spheroids, scanning electron microscopy, transmission electron microscopy, and multiphoton microscopy were used to obtain high-resolution 3D images of HeLa spheroids. Next, pairing high-resolution optical characterization techniques with flow cytometry, we quantitatively compared the penetration of doxorubicin, quantum dots, and synthetic micelles into 3D HeLa spheroid versus HeLa cells grown in a traditional two-dimensional culturing system. Our data revealed that 3D cultured HeLa cells acquired several clinically relevant morphologic and cellular characteristics (such as resistance to chemotherapeutics) often found in human solid tumors. These characteristic, however, could not be captured using conventional two-dimensional cell culture techniques. This study demonstrated the remarkable versatility of HeLa spheroid 3D imaging. In addition, our results revealed the capability of HeLa spheroids to function as a screening tool for nanoparticles or synthetic micelles that, due to their inherent size, charge, and hydrophobicity, can penetrate into solid tumors and act as delivery vehicles for chemotherapeutics. The development of this image-based, reproducible, and quantifiable in vitro HeLa spheroid screening tool will greatly aid future exploration of chemotherapeutics and nanoparticle delivery into solid tumors.

MiR-1-5p is down-regulated in gallbladder carcinoma and suppresses cell proliferation, migration and invasion by targeting Notch2.

BACKGROUND: Numerous studies have demonstrated that aberrant microRNAs (miRNAs) are involved in tumorigenesis and tumor progression. Nevertheless, the precise role of miR-1-5p in gallbladder carcinoma cell growth and metastasis remains not fully revealed. MATERIAL AND METHODS: The levels of miR-1-5p were detected in gallbladder carcinoma tissues and cell lines using qRT-PCR method. A series of functional assays, including cell proliferation, colony formation, wound healing and Transwell invasion were conducted using miR-1-5p or miR-1-5p inhibitor transfected cells. RESULTS: MiR-1-5p was remarkably down-regulated in gallbladder carcinoma tissues and cell lines compared to normal. In addition, over-expression of miR-1-5p markedly suppressed the growth, migration and invasion of gallbladder carcinoma cell. Conversely, down-expression of miR-1-5p facilitated gallbladder carcinoma cell proliferation and aggressiveness. Mechanistic investigations demonstrated that neurogenic locus notch homolog protein 2 (Notch2) was the directly target of miR-1-5p and Notch2 mediated the inhibitory effect of miR-1-5p in gallbladder carcinoma cell growth and aggressiveness. CONCLUSION: Our findings demonstrated that miR-1-5p acted as a suppressive miRNA and played vital roles in the growth, migration and invasion of gallbladder carcinoma cell through targeting Notch2.

Association of fibrinogen and fibrinogen gene beta148 and beta854 polymorphisms with coronary heart disease.

BACKGROUND: The aim of this study was to observe the association between fibrinogen C148T, G854A polymorphisms and plasma fibrinogen levels in a large cohort of Chinese patients with coronary heart disease (CHD). METHODS: Fibrinogen gene beta148/beta854 polymorphisms were screened and plasma fibrinogen levels and lipids were measured in patients with angiographically confirmed CHD (n = 836) and in controls without CHD (n = 418). RESULTS: Age, sex, smoking, hypertension, diabetes mellitus, blood lipids and fibrinogen levels were related to CHD (all p < 0. 05) while the frequencies of fibrinogen beta148 and beta854 alleles, gene and genotypes between the two groups were similar (all p > 0.05). CONCLUSION: This study demonstrates that the plasma fibrinogen level, but not fibrinogen beta148 and beta854 genotypes, was associated with CHD in the Chinese population.

Superparamagnetic iron oxide nanoparticles stabilized by alginate: pharmacokinetics, tissue distribution, and applications in detecting liver cancers.

The objectives of this study were to describe the pharmacokinetics and tissue distribution of superparamagnetic iron oxide nanoparticle (SPIO) stabilized with alginate (SPIO-alginate), and investigate its potential in detecting liver cancers as a newly developed magnetic resonance (MR) contrast agent. Pharmacokinetics and tissue distribution of SPIO-alginate were investigated in Sprague-Dawley rats. The results showed that SPIO-alginate was eliminated rapidly from serum with the half-life of 0.27 h at 109.5 micromol Fe/kg and accumulated dominantly in liver and spleen with a total percentage of more than 90% of dose after intravenous injection. The studies of pharmacokinetics and distribution of SPIO-alginate in rats indicated the MR contrast agent, based on SPIO, mainly accumulating in targeting organs that contain phagocytosing cells, i.e. liver and spleen. The efficacies in detecting hepatocellular carcinoma (HCC) of rat with primary liver cancer and xenograft liver cancers of rabbit were investigated before and after injection of SPIO-alginate. The signal intensity of liver parenchyma in rabbit with VX2 tumor after injection of SPIO-alginate was reduced sharply resulting in a significant contrast between liver parenchyma and tumor. Detection of the HCC in rat model was also demonstrated. The present study provides evidence that SPIO-alginate might have the ability to improve the detection of liver tumors as an MR contrast agent, and the efficacy is associated with the SPIO specifically located in Kupffer cells in hepatic sinusoid.

Studies on the effects of metal ions and counter anions on the aggregate behaviors of meso-tetrakis(p-sulfonatophenyl)porphyrin by absorption and fluorescence spectroscopy.

The aggregation behaviors of meso-tetrakis(p-sulfonatophenyl)porphyrin (TPPS) in the function of metal ions and their counter anions (Cl(-), SO4(2-), and NO3(-)) were investigated by absorption, fluorescence spectroscopy and resonance scattering spectrum. It was shown that the TPPS J-aggregates could be effectively promoted by metal ions under lower ionic strength. Moreover, the prominent effects of counter ions (Cl(-), SO4(2-), and NO3(-)) on TPPS J- and/or H-aggregate formation at higher ionic strength were observed. These results suggested that the counter anions play a significant role in the formation of TPPS J- and/or H-aggregates and their conversion each other. Very interestingly, the absorption spectrum of metal ions investigated except for Co2+ leaves a WINDOW from ca. 450 to 550 nm centered at 490 nm in which the absorption of Cu2+ or Ni2+ ions per se was very weak. The spectrum window might be really significant in avoiding possible spectrum interferences when porphyrins are chosen as spectrometric reagents for the determination of metal ions based on J-aggregation.

Preparation and characterization of superparamagnetic iron oxide nanoparticles stabilized by alginate.

SPION with appropriate surface chemistry have been widely used experimentally for numerous in vivo applications. In this study, SPION stabilized by alginate (SPION-alginate) were prepared by a modified coprecipitation method. The structure, size, morphology, magnetic property and relaxivity of the SPION-alginate were characterized systematically by means of XRD, TEM, ESEM, AFM, DLS, SQUID magnetometer and MRI, respectively, and the interaction between alginate and iron oxide (Fe(3)O(4)) was characterized by FT-IR and AFM. The results revealed that typical iron oxide nanoparticles were Fe(3)O(4) with a core diameter of 5-10 nm and SPION-alginate had a hydrodynamic diameter of 193.8-483.2 nm. From the magnetization curve, the Ms of a suspension of SPION-alginate was 40 emu/g, corresponding to 73% of that of solid SPION-alginate. This high Ms may be due to the binding of Fe(3)O(4) nanoparticles to alginate macromolecule strands as visually confirmed by AFM. SPION-alginate of several hundred nanometers was stable in size for 12 months at 4 degrees C. Moreover, T1 relaxivity and T2 relaxivity of SPION-alginate in saline (1.5 T, 20 degrees C) were 7.86+/-0.20 s(-1) mM(-1) and 281.2+/-26.4 s(-1) mM(-1), respectively.

[Advancement in the methods for gene dosage analysis].

Gene dosage determination is increasingly important for the study of both genome variation and rearrangement associated with complex diseases. Large genomic duplications and deletions are increasingly found as the causes. Methods such as PCR or sequencing are usually qualitative rather than quantitative. Thus, these methods can not detect large genomic duplications or deletions. Therefore, searching for a gene dosage method which is reliable, sensitive and high-throughput becomes imperative. Many high-performance technologies have been developed for gene dosage analyses in the recent years. There are generally three categories of methods including cytogenetic, Southern or dot blotting, or PCR amplification. Recent development in these techniques have been introduced and discussed in this review, which will help people to choose a suitable method for different research.

[Cationic liposomes loaded with doxorubicin targeting to the tumor neovasculature in vitro].

This study was conducted to investigate the in vitro characteristics of cationic liposomes composed of 3beta-[N-[2-(N', N'-dimethylamino) ethyl] carbamoyl] cholesterol (DC-Chol) and dipalmitoylphosphatidylcholine loaded with doxorubicin (DXR), and to provide useful information for the in vivo tumor vascular targeting of cationic liposomes. Cationic liposomes composed of different amounts of DC-Chol (0 mol%, 10 mol%, 25 mol%, 50 mol%) were loaded with the conventional anti-cancer drug doxorubicin. Their size, zeta potential, encapsulation efficiency, and DXR release in vitro were investigated. Moreover, their uptake by rat aortic endothelial cells (RAECs) was observed at 15 min, 30 min, 1 h, and 4 h of incubation. FITC-Dextran was i.v. injected to the H22 tumor-bearing KM mice to stain the neovasculature. The characteristics of resulting DXR-loaded cationic liposomes were in stable characteristics with particle sizes around 100 - 200 nm and capsulation efficiency greater than 90%. Increased cationic lipid led to enhanced zeta potential, and meanwhile it also resulted in quick release of the loaded drug, indicating increased slits or pores on the membrane upon the addition of DC-Chol. RAECs could more avidly take up DXR-loaded cationic liposomes when the content of DC-Chol increased in the liposomes, and DXR were quickly released in the cytoplasm and transported to the nuclei. The neovasculature stained by FITC-Dextran was clearly observed. DXR-cationic liposomes composed of DC-Chol could be used for tumor vascular targeting in vivo for further study.

H-phosphonate-mediated sulfonylation of heteroaromatic N-oxides: a mild and metal-free one-pot synthesis of 2-sulfonyl quinolines/pyridines.

A smart H-phosphonate-mediated synthetic strategy for the sulfonylation of heteroaromatic N-oxides has been developed, by which a large variety of 2-sulfonyl quinolines/pyridines were synthesized starting from easily available sulfonyl chlorides, diisopropyl H-phosphonate and pyridine/quinoline N-oxides in one pot under metal-free conditions at room temperature.

[Beta-blocker therapy in the management of malignant ventricular arrhythmia in patients with acute myocardial infarction].

OBJECTIVE: To evaluate the clinical effectiveness of beta-blocker therapy on malignant ventricular arrhythmia in patients with acute myocardial infarction (AMI). METHODS: Beta-blockers, atenolol or betaloc, were given at the doses of 3.125 to 12.500 mg twice or 3 times a day (Bid or Tid) for management of malignant ventricular arrhythmia in 6 patients with AMI on the basis of conventional therapy. Increasing dosage of 25 to 50 mg was later initiated according to the patients' condition. In 2 cases that failed to respond to conventional antiarrhythmic, esmolol was administered via intravenous injection (5-10 mg) to control malignant ventricular arrhythmia within approximately 30 min, followed by a 2-day course of intravenous infusion at the rate of 1 to 2 mg/min. RESULTS: Five AMI patients survived while death occurred in 1 case due to heart failure. No deterioration of the cardiac function or proarrhythmic effect was observed in the 5 survival cases, but the occurrence of transient hypotension in 2 cases in the early stage of beta-blocker application and death due to cardioc insufficiency in one. CONCLUSION: Adequate use of beta-blockers is necessary in the early stage of AMI for effective control of malignant ventricular arrhythmia and lowering the mortality.

On Positive Solutions for the Rational Difference Equation Systems x n+1 = A/x n y n (2), and y n+1 = By n /x n-1 y n-1.

Our aim in this paper is to investigate the behavior of positive solutions for the following systems of rational difference equations: x n+1 = A/x n y n (2), and y n+1 = By n /x n-1 y n-1, n = 0,1,…, where x -1, x 0, y -1, and y 0 are positive real numbers and A and B are positive constants.

[Effects of light condition on structure and photosynthetic characteristics of leaves in 'Hanfu' apple].

By using microscope technique and gas exchange method, the effects of light conditions on structure and photosynthetic characteristics of the leaves were studied with potted and fielded 'Hanfu' apple as materials. The results showed that the palisade tissue, spongy tissue and the total leaf thickness of 'Hanfu' apple was declined under the weak light environment, the palisade tissue were declined by 34.5% (pot) and 25.0% (field), and the total leaf thickness were declined by 27.1% (pot) and 18.3% (field). The light compensation point (LCP) of the field shading leaves was lowest (30.8 +/- 1.3 micromol x m(-2) x s(-1)), the saturation point (LSP) in full light was 22.7% (pot) and 48.2% (field) higher than in shading, respectively. The adaptability of the potted 'Hanfu' apple leaves built under different light conditions had different resistivity after exposing to high light, the startup time of maximum photosynthetic rates (15.4 micromol x m(-2) x s(-1) in full light and 12.7 micromol x m(-2) x s(-1) in shading) were different, which was 23 min and 33 min, respectively. Long-time shading impacted on the quality and photosynthetic capacity of 'Hanfu' apple leaves.

Investigation on solvation and protonation of meso-tetrakis(p-sulfonatophenyl)porphyrin in imidazolium-based ionic liquids by spectroscopic methods.

The solvation and protonation of the meso-tetrakis(p-sulfonatophenyl)porphyrin (TPPS) were investigated by spectroscopic methods in pure or mixed imidazolium-based ionic liquids: 1-butyl-3-methyl-imidazolium terafluoroborate ([MBIM]BF(4)), 1-butylimidazolium terafluoroborate ([HBIM]BF(4)), 1-butyl-imidazolium dodecylalkylbenzenesulfonate ([HBIM]DS), 1-butyl-imidazolium p-toluenesulfonate ([HBIM]TS) and 1-butyl-imidazolium methylsulfonate ([HBIM]MS). Compared with absorption properties of TPPS in aqueous solution, Soret band of TPPS monomer was obviously red-shifted in the ionic liquids, while special absorption of TPPS J-aggregates was located at higher energy level, 483 nm and 702 nm, in protonic ionic liquids (PILs) [HBIM]BF(4). Next, the protonation of TPPS in aprotonic ionic liquids (AILs, i.e., [MBIM]BF(4)) is dependent not only on the concentration of protonic ionic liquids as proton sources, but also on the characteristic of anion and viscosity of PILs. The proton transfer constants between TPPS and four protonic ionic liquids are (2.32 +/- 0.23) x 10(2) for [HBIM]BF(4), (1.52 +/- 0.08) x 10(2) for [HBIM]MS, (1.12 +/- 0.21) x 10(2) for [HBIM]DS and (0.84 +/- 0.45) x 10(2) for [HBIM]TS, respectively.

Magnetic targeting after femoral artery administration and biocompatibility assessment of superparamagnetic iron oxide nanoparticles.

Ferrofluids are attractive candidates for magnetic targeting system because of their fluidity and magnetism. The magnetic nanoparticles in ferrofluids should have combined properties of superparamagnetic behavior, target localization, and biocompatibility. The magnetic targeting and biocompatibility of superparamagnetic iron oxide nanoparticles stabilized by alginate (SPION-alginate) was investigated in vitro and in vivo. The localization of SPION-alginate by an external magnetic field in vitro was quantitatively evaluated by determining the iron content, and the results revealed that the localization ratio of SPION-alginate was 56%. Magnetic targeting of the SPION-alginate after femoral artery administration with the magnetic field in rats was quantitatively investigated by iron content and qualitatively confirmed by histological evaluation and magnetic resonance imaging. The ratio of iron content between the target site and the nontarget site were 8.88 at 0.5 h and 7.50 at 2 h, respectively. The viability of RAW264.7 cells and L929 cells was apparently unaltered upon exposure to SPION-alginate. The incubation with erythrocytes indicated that the SPION-alginate did not induce erythrocytes hemolysis and aggregation. In conclusions, the SPION-alginate had magnetic targeting with an external magnetic field and did not be detained at the injection site without the magnetic field. The SPION-alginate was generally considered to be biocompatible in cytotoxicity and hemolysis aspects.