Co-treatment of betulin and gefitinib is effective against EGFR wild-type/KRAS-mutant non-small cell lung cancer by inducing ferroptosis.

Clinical trials suggest that non-small-cell lung cancer (NSCLC) patients with KRAS mutations and wild-type EGFR have reduced benefits from gefitinib treatment. Ferroptosis is a new form of cell death that plays an important role in mediating the sensitivity of EGFR-TIKs. Here, we explored the antitumor ability of gefitinib in combination with betulin to overcome drug resistance through ferroptosis in wild-type EGFR/KRAS-mutant NSCLC cells. A549 and H460 cells were treated with gefitinib and betulin, and cell viability, apoptosis, and migration ability were assessed using the CCK-8 assay, flow cytometry, and wound-healing assay, respectively. Several cell death inhibitors were used to study the form of cell death. Ferroptosis-related events were detected by performing reactive oxygen species (ROS) and iron level detection, malondialdehyde (MDA) assay, and glutathione (GSH) assay. EMT-associated proteins and ferroptosis-related proteins were detected by using western blotting. A xenograft model was constructed in vivo to investigate the role of the combination treatment of betulin and gefitinib in NSCLC tumor growth. Gefitinib in combination with betulin exhibited antagonistic effects on cellular viability and induced cell apoptosis. It also induced ROS accumulation, lipid peroxidation, and GSH depletion and induced ferroptosis-related gene expression. Moreover, ferroptosis inhibitors, but not inhibitors of other forms of cell death, abrogated the effect of gefitinib in combination with betulin. Moreover, it also inhibited the tumor growth of NSCLC in vivo. Our findings suggest that gefitinib in combination with betulin is a novel therapeutic approach to overcome gefitinib resistance in EGFR wild-type/KRAS-mutant NSCLC cells by inducing ferroptosis.

Rapid, controllable fabrication of regular complex microarchitectures by capillary assembly of micropillars and their application in selectively trapping/releasing microparticles.

A simple strategy to realize new controllable 3D microstructures and a novel method to reversibly trapping and releasing microparticles are reported. This technique controls the height, shape, width, and arrangement of pillar arrays and realizes a series of special microstructures from 2-pillar-cell to 12 cell arrays, S-shape, chain-shape and triangle 3-cell arrays by a combined top down/bottom up method: laser interference lithography and capillary force-induced assembly. Due to the inherent features of this method, the whole time is less than 3 min and the fabricated area determined by the size of the laser beam can reach as much as 1 cm(2) , which shows this method is very simple, rapid, and high-throughput. It is further demonstrated that the 'mechanical hand'-like 4-cell arrays could be used to selectively trap/release microparticles with different sizes, e.g., 1.5, 2, or 3.5 µm, which are controlled by the period of the microstructures from 2.5 to 4 µm, and 6 µm. Finally, the 'mechanical hand'-like 4-cell arrays are integrated into 100 µm-width microfluidic channels prepared by ultraviolet photolithography, which shows that this technique is compatible with conventional microfabrication methods for on-chip applications.

[Inhibitory effects of Bellamya aeruginosa on common algae in freshwater blooms]. / 铜锈环棱螺对水华中常见藻类的抑制效应.

The increasingly frequent algal blooms in freshwater have become a major environmental problem in the world. In recent years, algae removal by the biological method is receiving more attention for its eco-friendly characteristics. In this study, we examined the effects of Bellamya aeruginosa, a common macrobenthic snail in eutrophic lakes in China, on the growth and photosynthesis activities of the common algae occurred in freshwater blooms, including cyanobacterium Microcystis aeruginosa, coupled with green algae Chlorella vulgaris and Scenedesmus obliquus. The main aims were to clarify the interactive relationships between B. aeruginosa and algae, and to verify feasibility of using B. aeruginosa as an algal-removing organism. The results showed that B. aeruginosa could feed a large amount of algae cells in a short period after inoculation, and reached the maximal removal rate of toxic and non-toxic M. aeruginosa as well as S. obliquus within 12 hours, which were 73.7%, 73.2%, and 51.1%, respectively. Furthermore, its feeding on C. vulgaris was stronger than on other algae, with the removal rate reaching 99.2% by the end of the experiment. The microcystins produced by the toxic M. aeruginosa accumulated in the body of B. aeruginosa induced the histopathological changes in the liver tissue, and thereby hindered the feeding of B. aeruginosa. In the late stage of the experiment, the photosynthetic activities of the algal cells under each treatment were significantly lower than that in the control, indicating that the feeding of B. aeruginosa damaged algal cells and inhibited their proliferation. In addition, in the mixture of non-toxic M. aeruginosa and S. obliquus, the selective feeding of B. aeruginosa caused the dominance of non-toxic M. aeruginosa to be replaced by S. obliquus. Therefore, B. aeruginosa could inhibit the photosynthesis and reduce the biomass of algae through feeding, and thus would eliminate or mitigate the formation of algal blooms.

Reducing urinary tract infections among female clean room workers.

OBJECTIVES: A higher prevalence of urinary tract infection (UTI) was observed among clean room workers than among others in our previous study in 2001. We implemented intervention programs for reducing UTI and evaluated their effects 2 years later. METHODS: We conducted an intervention study in four factories in the industrial park where the previous study was conducted and recruited participants from women workers who received annual health examinations at the clinic of the park. The intervention included health education programs during the new employee orientation and seasonal on-the-job training. We also implemented other measures, including placing posters in the workplace and disseminating knowledge of UTI prevention through e-mail and oral communications. One-on-one education was provided to workers who were found to have UTI in the previous study. RESULTS: All the 1666 qualified workers, including 1414 clean room workers and 252 nonclean room workers, agreed to participate. We found a similar prevalence (both 0.8%) of symptomatic UTIs (patients with clinical symptoms, such as voiding frequency, urgency, and burning sensation during voiding) in clean room and nonclean room workers. In the 366 participants who also participated in the previous study, we found a significant decrease in the prevalence of UTI (from 9.8% to 1.6%) and significant increases in the prevalence of water intake and urine voiding, three times or more during a shift (p < 0.001 for all McNemar tests). CONCLUSIONS: The interventions had achieved behavior modification and decreases in the prevalence of UTI.

Prevalence of urinary tract infections and associated factors among pregnant workers in the electronics industry.

INTRODUCTION AND HYPOTHESIS: Pregnancy is a risk factor for urinary tract infection (UTI), and it has been shown that frequent urine voiding was a protecting factor against UTI for nonpregnant female cleanroom workers. We conducted a study to evaluate whether these findings also apply to pregnant women. METHODS: We recruited female workers in an industrial park who received an annual health examination between August 1 and September 31, 2003. From each participant, we collected a urine sample and obtained information through a questionnaire. RESULTS: A total of 2,062 workers, including 118 pregnant and 1,944 nonpregnant women, participated in the study. Pregnancy was a significant risk factor for both symptomatic (odds ratio [OR] = 6.33) and asymptomatic (OR = 2.13) UTIs. Urine voiding three or more times during a shift was a significant protective factor for asymptomatic UTI (OR = 0.40). CONCLUSIONS: UTI is common among pregnant cleanroom workers, and frequent voiding appears to be a protecting factor.