Doxorubicin resistance in breast cancer xenografts and cell lines can be counterweighted by microRNA-140-3p, through PD-L1 suppression

Background. Doxorubicin, a first-line chemotherapeutic drug for breast cancer, kills cancer cells by inducing DNA-crosslinking damage. Dysregulated micro-RNA (miRNA) is associated with the drug resistance of tumors. However, little is known about the effect of miRNA-140-3p on DOX resistance of breast cancer. Methods. The miRNA microarray was used to sequence the transcripts of DOX-chemoresistant breast cancer tissues and DOX-chemosensitive tissues. Then, the breast cancer tissue chip in the GEO database was also analyzed to screen the target gene. Flow cytometry, in situ hybridisation (ISH), immunohistochemistry (IHC), Western blot, cell proliferation assay, real-time PCR analyses (qRT-PCR), and pull-down assay were used to explore the effects of miRNA-140-3p and programmed death ligand-1 (PD-L1) on the chemoresistance of DOX-resistant breast cancer cells treated with DOX. In vivo, the DOX-resistant breast cancer cell lines treated with miRNA-140-3p overexpression were injected subcutaneously into mice to construct breast cancer subcutaneous xenograft tumor models. Results. Based on miRNA microarray, GEO database, and bioinformatics analysis, it was found that miRNA-140-3p and PD-L1 are the core molecules in the DOX resistance regulatory network in breast cancer, and lower miRNA-140-3p and higher PD-L1 expression levels were observed in DOX-resistant breast cancer tissues and cells. IHC results showed that compared with breast cancer tissues with high miRNA-140-3p expression, PD-L1 protein expression levels in breast cancer tissues with low miRNA-140-3p were significantly higher (P<0.01). Moreover, compared with DOX-sensitive tissues, the levels of PD-L1 protein expression in DOX-resistant tissues were significantly higher (P<0.01). In in vitro and in vivo experiments, the introduction of miRNA-140-3p decreased PD-L1 expression. Mechanically, we found that the MCF7/DOX and HS598T/DOX cells pretreated with miRNA140-3p inhibitor or exosomes containing PD-L1 have higher stemness and lower apoptosis rate, which can be abrogated by co-treating cells with anti-PD-L1 antibody or miRNA-140-3p mimic. Conclusions. MiRNA-140-3p can suppress PD-L1 expression in breast cancer cell-derived exosomes, thereby attenuating the chemoresistance induced by DOX in breast cancer

The influence of local officials' promotion incentives on carbon emission in Yangtze River Delta, China

China's carbon emissions is heavily influenced by economic growth, which can be largely related to the local officials' promotion incentives. The current study was conducted to test the hypothesis that the influence of local officials' individual characteristics on carbon emissions was driven by the promotion incentives. Yangtze River Delta where carbon emissions accounted for around 13.95% of China's total emissions was selected as the research area. The multiple linear regression model was applied to determine the relationship between local officials' characteristics and total carbon emissions and carbon emissions from different sectors. The results indicated that local officials' promotion source, tenure and age significantly influenced the total carbon emission. Despite insignificance influence of officials' academic level on carbon emissions, the professional background in economics and management had a significant influence on carbon reduction. Our results indicated the importance of local officials' promotion incentives for carbon emission in China. Therefore, low carbon development should be included as an important part of official promotion system

The “Regulator” Function of Viruses on Ecosystem Carbon Cycling in the Anthropocene

Viruses act as “regulators” of the global carbon cycle because they impact the material cycles and energy flows of food webs and the microbial loop. The average contribution of viruses to the Earth ecosystem carbon cycle is 8.6‰, of which its contribution to marine ecosystems (1.4‰) is less than its contribution to terrestrial (6.7‰) and freshwater (17.8‰) ecosystems. Over the past 2,000 years, anthropogenic activities and climate change have gradually altered the regulatory role of viruses in ecosystem carbon cycling processes. This has been particularly conspicuous over the past 200 years due to rapid industrialization and attendant population growth. The progressive acceleration of the spread and reproduction of viruses may subsequently accelerate the global C cycle

Low-Temperature Gas Plasma Combined with Antibiotics for the Reduction of Methicillin-Resistant \u3ci\u3eStaphylococcus aureus\u3c/i\u3e Biofilm Both in Vitro and in Vivo

Biofilm infections in wounds seriously delay the healing process, and methicillin-resistant Staphylococcus aureus is a major cause of wound infections. In addition to inactivating micro-organisms, low-temperature gas plasma can restore the sensitivity of pathogenic microbes to antibiotics. However, the combined treatment has not been applied to infectious diseases. In this study, low-temperature gas plasma treatment promoted the effects of different antibiotics on the reduction of S. aureus biofilms in vitro. Low-temperature gas plasma combined with rifampicin also effectively reduced the S. aureus cells in biofilms in the murine wound infection model. The blood and histochemical analysis demonstrated the biosafety of the combined treatment. Our findings demonstrated that low-temperature gas plasma combined with antibiotics is a promising therapeutic strategy for wound infections

A comprehensive insight into the effects of acidification on varied-sized pores in different rank coals

Elucidating the evolution law of coal pore structure under acidification is crucial for guiding the practical application of acidizing technology and improving the production of coalbed methane. To comprehensively investigate the influence of acidification on varied-sized pores in different rank coals, in this study, fat coal, meagre coal and anthracite coal were collected and acidified with a mixed solution composed of hydrochloric acid (9 wt%) and hydrofluoric acid (3 wt%). An approach integrating low-pressure CO2 adsorption (LPGA-CO2), low-temperature N2 adsorption (LTGA-N2) and Mercury intrusion porosimetry (MIP) was adopted to fully characterize the varied-sized pore structure before and after acidification to eliminate the limitations of single method. The results demonstrated that acid treatment improved the pore opening degree and connectivity in coal, but had essentially no effect on the pore shape. After acidification, all the coal samples showed significant increases in the porosity and total pore volume, which was mainly contributed by the numerous newly formed large mesopores and macropores, especially the macropores (with an average contribution rate of 74.59%). Taken as a whole, acid treatment had the largest impact on macropores, followed by mesopores, and the smallest impact on micropores. In addition, the variation trend of total specific surface area (SSA) under acidification was primarily determined by micropores. For the three different rank coals selected in this study, the total SSA of fat coal (PM) was more easily affected by acidification and had the largest percentage increase after acid treatment, followed by anthracite coal (YM), while that of meagre coal (LA) decreased slightly. This difference was driven primarily by the different variation trend of micropore SSA in different rank coals. After acidification, the SSA of ultra-micropores and super-micropores all increased in fat coal (PM) and anthracite coal (YM), whereas for meagre coal (LA), although ultra-micropores SSA increased, super-micropores SSA decreased, which ultimately led to the slight decrease of its micropore SSA. Moreover, the total pore volume increment of coal was closely related to the macropore volume increment under acidification, but not significantly related to the coal maturity,which might indicate that, compared with coal rank, the mineral content in coal might be a more important consideration when measuring the applicability of acidification technology

Clinical Characteristics of 26 Human Cases of Highly Pathogenic Avian Influenza A (H5N1) Virus Infection in China

BACKGROUND: While human cases of highly pathogenic avian influenza A (H5N1) virus infection continue to increase globally, available clinical data on H5N1 cases are limited. We conducted a retrospective study of 26 confirmed human H5N1 cases identified through surveillance in China from October 2005 through April 2008. METHODOLOGY/PRINCIPAL FINDINGS: Data were collected from hospital medical records of H5N1 cases and analyzed. The median age was 29 years (range 6-62) and 58% were female. Many H5N1 cases reported fever (92%) and cough (58%) at illness onset, and had lower respiratory findings of tachypnea and dyspnea at admission. All cases progressed rapidly to bilateral pneumonia. Clinical complications included acute respiratory distress syndrome (ARDS, 81%), cardiac failure (50%), elevated aminotransaminases (43%), and renal dysfunction (17%). Fatal cases had a lower median nadir platelet count (64.5 x 10(9) cells/L vs 93.0 x 10(9) cells/L, p = 0.02), higher median peak lactic dehydrogenase (LDH) level (1982.5 U/L vs 1230.0 U/L, p = 0.001), higher percentage of ARDS (94% [n = 16] vs 56% [n = 5], p = 0.034) and more frequent cardiac failure (71% [n = 12] vs 11% [n = 1], p = 0.011) than nonfatal cases. A higher proportion of patients who received antiviral drugs survived compared to untreated (67% [8/12] vs 7% [1/14], p = 0.003). CONCLUSIONS/SIGNIFICANCE: The clinical course of Chinese H5N1 cases is characterized by fever and cough initially, with rapid progression to lower respiratory disease. Decreased platelet count, elevated LDH level, ARDS and cardiac failure were associated with fatal outcomes. Clinical management of H5N1 cases should be standardized in China to include early antiviral treatment for suspected H5N1 cases

Contagion effect analysis of financial crisis in soybean futures markets based on copula functions

Conference Name:2012 International Applied Mechanics, MechatronicsAutomation and System Simulation Meeting, AMMASS 2012. Conference Address: Hangzhou, China. Time:June 24, 2012 - June 26, 2012.Using five kinds of Copula functions to investigate the changes of correlations among soybean futures in Tokyo Grain Exchange, Chicago Board of Trade and Dalian Commodity Exchange market before and after the financial crisis caused by American subprime mortgage, this paper verifies the existence of contagion effect of this crisis in the international soybean futures markets. 漏 (2012) Trans Tech Publications, Switzerland

Correlation analysis among international soybean futures markets based on D-vine pair-Copula method

Conference Name:Computer Science and Information Engineering, CSIE 2012. Conference Address: Zhengzhou, China. Time:May 19, 2012 - May 20, 2012.International Science and Education Researcher Association; VIP Information Conference Center; Beijing Gireda Research CenterThis paper uses D-vine pair-Copula, T-Copula and Gaussian- Copula to study the correlations among three soybean futures markets in Tokyo Grain Exchange (TGE), Chicago Board of Trade (CBOT) and Dalian Commodity Exchange (DCE). The obtained results show: (1) the correlation between soybean futures markets in TGE and DCE is the highest no matter which method is used; (2) the correlations obtained with pair-Copula method is lower than the other corresponding correlations obtained by T-Copulas and Gaussian Copula, which indicates D-vine pair-Copula method gives net correlation between two variables by getting rid of the impacts of other variables. 漏 2012 Springer-Verlag GmbH