Highly water-dispersible PCN nanosheets as light-controlled lysosome self-promoting escape type non-cationic gene carriers for tumor therapy.

The construction of non-viral gene delivery faces two major challenges: cytotoxicity caused by high cationic charge units and easy degradation by lysosomes. Herein, highly water-dispersible polymeric carbon nitride (PCN) nanosheets were utilized as the core to construct a light-controlled non-cationic gene delivery system with sufficient lysosomal escape ability. In this system, these nanosheets exhibited efficient DNA condensation, outstanding biocompatibility, transfection tracking, light responsiveness and high transfection efficiency. Once PCN-DNA was taken up by the tumor cells, the accumulated ROS generated by photosensitizers (PSs) under light irradiation would destroy the structure of lysosomes, promote the escape of PCN-DNA and increase the efficiency of gene transfection. Simultaneously, the gene transfection process could be tracked in real time through fluorescence imaging technology, which was conducive to investigate the transfection mechanism. In vitro and in vivo experiments further confirmed that PCN nanosheets loaded with the P53 gene were beneficial to the regeneration of the P53 apoptotic pathway, increased tumor sensitivity to PSs, and further induced tumor cell apoptosis. In summary, the highly water-dispersible PCN nanosheets were applied to light-controlled self-escaping gene delivery for the first time, and tumor gene therapy was successfully realized.

Theoretical investigation on the low-energy isomer identification, structural evolution, stability, and electronic properties of Al10-xBex (x = 1-9) nanoalloys.

Numerous isomeric equilibrium structures have been identified for the Al10-xBex (x = 1-9) nanoalloy clusters by using the stochastic search procedure in combination with density functional theory calculations. The relative stability and various electronic properties of the lowest-energy Al10-xBex (x = 0-10) clusters have been systematically studied by using the B3LYP and CCSD(T) methods with the aug-cc-pVDZ basis set. The evolution of the binding energies, the second difference in energy, HOMO-LUMO gaps, vertical detachment energies, vertical ionization potentials, vertical electron affinities, and hardness with the increasing number of Be atoms in the most stable Al10-xBex (x = 0-10) clusters demonstrates that the global minimum of Al8Be2 cluster possesses a special stability. Thus, the electronic structure of the lowest-energy Al8Be2 cluster has been also detected in detail. In addition, it is found that the polarizabilities gradually decrease with increasing number of Be atoms, and the charges always transfer from Al to Be atoms in these nanoalloy clusters. We hope this work could provide helpful insight into the composition-dependent electronic properties of BeAl alloy at the nanoscale, serving as powerful guidelines for future experimental research.

Evaluation of the zein/inorganics composite on biocompatibility and osteoblastic differentiation.

We have previously studied the biocompatibility and mechanical properties of porous zein scaffolds. We based the study on the concept that composite scaffold materials, especially when combined with inorganic materials, are more suited to the mechanical and physiological demands of the host tissue than individual scaffold materials. We investigated the effect of zein/inorganic composite on the physical and biological properties of porous zein scaffolds, which were fabricated by salt-leaching. The composite was prepared by immersion in simulated body fluid. The hydroxyapatite (HA)-coated zein scaffold had the same porosity as the zein scaffold (over 75%). Using scanning electron microscopy, it was established that the morphology of pores located on the surface and within the porous scaffolds showed equally good pore interconnectivity with zein. However, the compressive Young's modulus decreased from 240.1+/-96.8 to 34.4+/-12.6MPa, and compressive strength decreased from 7.8+/-1.2 to 4.2+/-0.8MPa. From the in vitro test with human bone marrow stroma cells, the osteoblastic differentiation on the surface of the HA-coated zein scaffold was increased, as expressed by the alkaline phosphatase activity and reverse transcription-polymerase chain reaction analysis for marker genes. From both the mechanical and biological evaluations, the HA-coated zein scaffold was found to be the optimal biomaterial for bone tissue engineering.

[Concentrations of PCDD/Fs in the atmosphere of Chongqing City and its seasonal variation].

As a comprehensive monitoring survey on polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in Chongqing, 20 ambient air samples taken from 5 locations in four seasons were studied. The PCDD/F TEQ concentrations varied from 0.017 pg x m(-3) to 0.21 pg x m(-3). The average value was (0.094 +/- 0.054) pg x m(-3). The PCDD/F concentrations varied by locations and seasons, and the orders were: urban area > suburban area > background area, and Winter > Spring > Autumn > Summer. The concentrations of PCDD/Fs were 2.2-4.6 times higher in the winter than during the summer. The PCA results indicated that PCDD/F homologue pattern varied by seasons. The PCDD/F homologue pattern in particle dominated in winter and spring, and the pattern in gas dominated in summer and autumn. The mass concentration of PCDD/F congener was significantly positively correlated with that of SO2, NO2, PM10 and TSP, and insignificantly negatively correlated with that of O3, respectively. The results showed that spatial distribution and seasonal variation of atmospheric PCDD/Fs in Chongqing was consistent with that of these conventional indicators, and the PCDD/Fs pollution was closely related with the emission sources of SO2, NO2, PM10 and TSP.

[Atmospheric emission of PCDD/Fs from secondary aluminum metallurgy industry in the southwest area, China].

Five secondary aluminum metallurgy enterprises in the southwest area of China were measured for emissions of PCDD/Fs. The results indicated that the emission levels of PCDD/Fs (as TEQ) were 0.015-0.16 ng x m(-3), and the average was 0.093 ng x m(-3) from secondary aluminum metallurgy enterprises. Emission factors of PCDD/Fs (as TEQ) from the five secondary aluminum metallurgy enterprises varied between 0.041 and 4.68 microg x t(-1) aluminum, and the average was 2.01 microg x t(-1) aluminum; among them, PCDD/Fs emission factors from the crucible smelting furnace was the highest. Congener distribution of PCDD/F in stack gas from the five secondary aluminum metallurgies was very different from each other. Moreover, the R(PCDF/PCDD) was the lowest in the enterprise which was installed only with bag filters; the R(PCDF/PCDD) were 3.8-12.6 (the average, 7.7) in the others which were installed with water scrubbers. The results above indicated that the mechanism of PCDD/Fs formation was related to the types of exhaust gas treatment device. The results of this study can provide technical support for the formulation of PCDD/Fs emission standards and the best available techniques in the secondary aluminum metallurgy industry.

[Atmospheric emission of PCDD/Fs from modern dry processing cement kilns with preheating in the southwest area, China].

Six cement kilns were measured for emissions of PCDD/Fs in the Southwest Area, China. The results indicated that the emission levels of PCDD/Fs were 0.0029-0.0062 ng-m(-3) (Average, 0.0043 ng X m(-3)) from cement kilns which did not burn solid waste, and 0.028 ng X m(-3) from co-processing sewage sludge in cement kiln. The levels of PCDD/Fs emissions from cement manufacturing in the Southwest Area were significantly below the national emissions standard (0.1 ng x m(-3)). Emission factors of PCDD/Fs from the six cement kilns varied between 0.0089 and 0.084 microg x t(-1) cement, which were near or below the lowest emission factor reported by UNEP in 2005. Moreover, the emission factor of PCDD/Fs from co-processing sewage sludge in cement kiln was 7.6 times of the average factors from the other five cement kilns. Moreover,congener distribution of PCDD/F in stack gas from the two types of cement kilns was very different. The results showed that modern dry process cement kilns with preheating have lower emissions of PCDD/Fs. This suggested that the product of co-processing solid waste in cement kilns should be largely enhanced in China in future.

Inhibiting wear particles-induced osteolysis with doxycycline.

AIM: To study the effect of doxycycline (DOX) on osteoclastogenesis, mature osteoclast fate and function, wear particles-induced osteoeolysis, and to provide some foundation for treating aseptic loosening and osteolysis after joint arthroplasty. METHODS: Osteoclasts were generated from mouse bone marrow monocytes with the receptor activator of NF-kappaB ligand and the macrophage colony stimulating factor. DOX at a concentration of 5, 10, 15, and 20 microg/mL was respectively added to the medium. Seven days later, the osteoclasts were determined through tartrate-resistant acid phosphatase (TRAP) staining. Mature osteoclasts were isolated from newborn rabbits and cultured for 3 d in 24-well plates or on bone slices. DOX at a concentration of 5, 10, 15, and 20 microg/mL was respectively added to the medium. After TRAP staining, the osteoclasts were counted, resorption on bone slices was quantified, and the area was calculated after toluidine blue and Mayer-hematoxylin staining. Polymethyl methacrylate (PMMA) or ultra-high molecular weight polyethylene (UHMWPE) particles were implanted on the calvariae of C57BL/J6 mice. DOX, at a dose of 2 and 10 mg x kg(-1) x d(-1), was respectively given intraperitoneally for 7 d. Seven days later, the calvariae were removed and processed for pathological analysis. RESULTS: DOX treatment effectively inhibited in vitro osteoclastogenesis, affected the fate of mature osteoclasts, and inhibited mature osteoclasts, causing bone resorption. In vivo data indicated that DOX strongly inhibited PMMA or UHMWPE-induced osteolysis and osteoclastogenesis. CONCLUSION: DOX can effectively inhibit osteoclastogenesis and affect mature osteoclast fate and suppress wear particles induced by osteolysis and osteoclastogenesis. DOX might be useful in the treatment or prevention of wear particles-induced osteolysis and aseptic loosening for its effect on osteoclast generation and mature osteoclast fate and function.

Sirolimus-eluting, bioabsorbable polymer-coated constant stent (Cura) in acute ST-elevation myocardial infarction: a clinical and angiographic study (CURAMI Registry).

BACKGROUND: There are safety concerns over the current polymer-based drug-eluting stents (DES) on the possible delayed healing process and adverse reactions to the polymer when drug elution is completed. Cura (Orbus Neich) is a sirolimus-eluting, bioabsorbable, polymer-coated constant stent. METHODS: From March 1 to June 30, 2005, Cura stent implantation was instituted as the default strategy for percutaneous coronary intervention in 49 consecutive ST-Elevation Myocardial Infarction (STEMI) patients (male 86%; average age 55 +/- 10 years; diabetes 31%). RESULTS: The angiographic success rate was 100%. In-hospital adverse events consisted of 1 in-hospital death (2% heart failure). A total of 27 patients (56%) underwent 8-month angiographic follow up. Binary restenosis occurred in 6 patients (22%), and late loss was 0.74 +/- 0.89 mm. At 9-month follow up, a total of 5 patients had 6 major adverse events (1 death, 1 reinfarction, and 4 target lesion revascularizations). There was no incidence of stent thrombosis. CONCLUSION: Cura stent implantation appears to be feasible and safe in the treatment of STEMI. However, the binary restenosis rate and late loss at angiographic follow up were similar to that of bare-metal stents, and therefore compare unfavorably with other proven benchmark DES.