I13 overrides resistance mediated by the T315I mutation in chronic myeloid leukemia by direct BCR-ABL inhibition

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by a BCR-ABL fusion gene. Imatinib has significantly improved the treatment of CML as a first-generation tyrosine kinase inhibitor (TKIs). The T315I mutant form of BCR-ABL is the most common mutation that confers resistance to imatinib or the second-generation TKIs, resulting in poor clinical prognosis. In this work, we assessed the effect of a potent histone deacetylase (HDAC) inhibitor, I13, on the differentiation blockade in CML cells harboring T315I-mutated and wild-type BCR-ABL by MTT assay, flow cytometery, cell colony formation assay, mRNA Sequencing, Quantitative real-time PCR and Western blotting analysis. We found that I13 possessed highly potent activity against T315I-mutated BCR-ABL mutant-expressing cells and wild-type BCR-ABL-expressing cells. I13 induced cell differentiation and significantly suppressed the proliferation of these CML cells via the cell cycle G0/G1-phase accumulation. Moreover, it was revealed that I13 triggered the differentiation of BaF3-T315I cells, which was attributed to the block of the chronic myeloid leukemia signaling pathway via the depletion of BCR-ABL that was mediated by the inhibition of HDAC activity presented by the acetylation of histones H3 and H4. Taken together, I13 efficiently depleted BCR-ABL in CML cells expressing the BCR-ABL-T315I mutation, which blocked its function, serving as a scaffold protein that modulated the chronic myeloid leukemia signaling pathway mediating cell differentiation. The present findings demonstrate that I13 is a BCR-ABL modulator for the development of CML therapy that can override resistance caused by T315I-mutated BCR-ABL

Albedo changes caused by future urbanization contribute to global warming

The replacement of natural lands with urban structures has multiple environmental consequences, yet little is known about the magnitude and extent of albedo-induced warming contributions from urbanization at the global scale in the past and future. Here, we apply an empirical approach to quantify the climate effects of past urbanization and future urbanization projected under different shared socioeconomic pathways (SSPs). We find an albedo-induced warming effect of urbanization for both the past and the projected futures under three illustrative scenarios. The albedo decease from urbanization in 2018 relative to 2001 has yielded a 100-year average annual global warming of 0.00014 [0.00008, 0.00021] °C. Without proper mitigation, future urbanization in 2050 relative to 2018 and that in 2100 relative to 2018 under the intermediate emission scenario (SSP2-4.5) would yield a 100-year average warming effect of 0.00107 [0.00057,0.00179] °C and 0.00152 [0.00078,0.00259] °C, respectively, through altering the Earth’s albedo

Urbanization and sustainability under transitional economies:a synthesis for Asian Russia

Spanning a vast territory of approximately 13 million km ^2 , Asian Russia was home to 38 million people in 2016. In an effort to synthesize data and knowledge regarding urbanization and sustainable development in Asian Russia in the context of socioeconomic transformation following the breakup of the Soviet Union in 1990, we quantified the spatiotemporal changes of urban dynamics using satellite imagery and explored the interrelationships between urbanization and sustainability. We then developed a sustainability index, complemented with structural equation modeling, for a comprehensive analysis of their dynamics. We chose six case cities, i.e., Yekaterinburg, Novosibirsk, Krasnoyarsk, Omsk, Irkutsk, and Khabarovsk, as representatives of large cities to investigate whether large cities are in sync with the region in terms of population dynamics, urbanization, and sustainability. Our major findings include the following. First, Asian Russia experienced enhanced economic growth despite the declining population. Furthermore, our case cities showed a general positive trend for population dynamics and urbanization as all except Irkutsk experienced population increases and all expanded their urban built-up areas, ranging from 13% to 16% from 1990 to 2014. Second, Asian Russia and its three federal districts have improved their sustainability and levels of economic development, environmental conditions, and social development. Although both regional sustainability and economic development experienced a serious dip in the 1990s, environmental conditions and social development continuously improved from 1990 to 2014, with social development particularly improving after 1995. Third, in terms of the relationships between urbanization and sustainability, economic development appeared as an important driver of urbanization, social development, and environmental degradation in Asian Russia, with economic development having a stronger influence on urbanization than on social development or environmental degradation

Prospects for the sustainability of social-ecological systems (SES) on the Mongolian plateau: five critical issues

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Roles of Economic Development Level and Other Human System Factors in COVID-19 Spread in the Early Stage of the Pandemic

We identified four distinct clusters of 151 countries based on COVID-19 prevalence rate from 1 February 2020 to 29 May 2021 by performing nonparametric K-means cluster analysis (KmL). We forecasted future development of the clusters by using a nonlinear 3-parameter logistic (3PL) model, and found that peak points of development are the latest for Cluster I and earliest for Cluster IV. Based on partial least squares structural equation modeling (PLS-SEM) for the first twenty weeks after 1 February 2020, we found that the prevalence rate of COVID-19 has been significantly influenced by major elements of human systems. Better health infrastructure, more restriction of human mobility, higher urban population density, and less urban environmental degradation are associated with lower levels of prevalence rate (PR) of COVID-19. The most striking discovery of this study is that economic development hindered the control of COVID-19 spread among countries in the early stage of the pandemic. Highlights: While richer countries have advantages in health and other urban infrastructures that may alleviate the prevalence rate of COVID-19, the combination of high economic development level and low restriction on human mobility has led to faster spread of the virus in the first 20 weeks after 1 February 2020

Roles of Economic Development Level and Other Human System Factors in COVID-19 Spread in the Early Stage of the Pandemic

We identified four distinct clusters of 151 countries based on COVID-19 prevalence rate from 1 February 2020 to 29 May 2021 by performing nonparametric K-means cluster analysis (KmL). We forecasted future development of the clusters by using a nonlinear 3-parameter logistic (3PL) model, and found that peak points of development are the latest for Cluster I and earliest for Cluster IV. Based on partial least squares structural equation modeling (PLS-SEM) for the first twenty weeks after 1 February 2020, we found that the prevalence rate of COVID-19 has been significantly influenced by major elements of human systems. Better health infrastructure, more restriction of human mobility, higher urban population density, and less urban environmental degradation are associated with lower levels of prevalence rate (PR) of COVID-19. The most striking discovery of this study is that economic development hindered the control of COVID-19 spread among countries in the early stage of the pandemic. Highlights: While richer countries have advantages in health and other urban infrastructures that may alleviate the prevalence rate of COVID-19, the combination of high economic development level and low restriction on human mobility has led to faster spread of the virus in the first 20 weeks after 1 February 2020

Urban Built-up Areas in Transitional Economies of Southeast Asia: Spatial Extent and Dynamics

Urban built-up area, one of the most important measures of an urban landscape, is an essential variable for understanding ecological and socioeconomic processes in urban systems. With an interest in urban development in transitional economies in Southeast Asia, we recognized a lack of high-to-medium resolution (<60 m) built-up information for countries in the region, including Vietnam, Laos, Cambodia and Myanmar. In this study, we combined multiple remote sensing data, including Landsat, DMSP/OLS night time light, MODIS NDVI data and other ancillary spatial data, to develop a 30-m resolution urban built-up map of 2010 for the above four countries. Following the trend analysis of the DMSP/OLS time series and the 2010 urban built-up extent, we also quantified the spatiotemporal dynamics of urban built-up areas from 1992 to 2010. Among the four countries, Vietnam had the highest proportion of urban built-up area (0.91%), followed by Myanmar (0.15%), Cambodia (0.12%) and Laos (0.09%). Vietnam was also the fastest in new built-up development (increased ~8.8-times during the 18-year study period), followed by Laos, Cambodia and Myanmar, which increased at 6.0-, 3.6- and 0.24-times, respectively