GPCR-like signaling mediated by smoothened contributes to acquired chemoresistance through activating Gli

BACKGROUND: Smoothened (Smo), which possesses a structural similarity with classic G-protein coupled receptors (GPCR), is the most important molecular target in Hedgehog (Hh) signaling system for developing anticancer drugs; however, whether Smo may transmit GPCR-like signaling to activate the canonical transcriptional factor Gli of Hh signaling system and consequently to be involved in the Gli-dependent biological events remains controversial. RESULTS: In this study, using the acquired chemoresistant cancer cell lines and their respective parental cells, we found that Smo may activate Gli through Gαi, Gβγ-JNK signaling axis, thereby promoting the Gli-dependent acquired chemoresistance. These observations were further complementarily strengthened by data obtained from chemosensitive cancer cells with artificially elevated Hh pathway activity. CONCLUSIONS: Hence, our data demonstrate that GPCR-like signaling mediated by Smo contributes to the acquired chemoresistance through activating the canonical Hh transcriptional factor Gli; therefore improving our knowledge of the nature of the signal transduction of Smo and the molecular mechanisms responsible for the acquired chemoresistance maintained by Hh pathway. Moreover, our data that JNK after activated by Smo-Gβγ signaling axis may stimulate the Gli activity and consequently promotes acquired chemoresistance expose a promising and potential target for developing anti-cancer drugs aimed at Hh pathway and for combating the acquired resistance raised by using of anti-cancer drugs targeting Smo

Analyzing and modeling the spatiotemporal dynamics of urban expansion: a case study of Hangzhou City, China

Understanding the spatiotemporal characteristics of urban expansion is increasingly important for assisting the decision making related to sustainable urban development. By integrating remote sensing (RS), spatial metrics, and the cellular automata (CA) model, this study explored the spatiotemporal dynamics of urban expansion and simulated future scenarios for Hangzhou City, China. The land cover maps (2002, 2008, and 2013) were derived from Landsat images. Moreover, the spatial metrics were applied to characterize the spatial pattern of urban land. The CA model was developed to simulate three scenarios (Business-As-Usual (BAU), Environmental Protection (EP), and Coordination Development (CD)) based on the various strategies. In addition, the scenarios were further evaluated and compared. The results indicated that Hangzhou City has experienced significant urban expansion, and the urban area has increased by 698.59 km2. Meanwhile, the spatial pattern of urban land has become more fragmented and complex. Hangzhou City will face unprecedented pressure on land use efficiency and coordination development if this historical trend continues. The CD scenario was regarded as the optimized scenario for achieving sustainable development. The findings revealed the spatiotemporal characteristics of urban expansion and provide a support for future urban development

Land surface temperature and its impact factors in Western Sichuan Plateau, China

The understanding influence of multiple factors variations on land surface temperature (LST) remains elusive. LST was retrieved by the atmospheric correction algorithms. Based on the correlation coefficients, stepwise regression analysis was developed to examine how multiple factors variability led to LST variations. The differences in LST between impact factors vary depending on time in a day. The elevation and land use types significantly affect the LST in sunny slope or shadow areas has a significantly quadratic curve correlation or a negative linear correlation with it, the influence of slope and aspect is not very significant. LST for forestland, grassland and bare land in the sunny slope and shadow area was the cubic polynomial related to its elevation. Normalized difference vegetation index (NDVI) and normalized difference moisture index (NDMI) effectively express LST in mountainous. LST and NDMI or NDVI have a significantly negative correlation, NDMI is more effective and more applicable for the expression of LST

Vegetation EVI changes and response to natural factors and human activities based on geographically and temporally weighted regression

The research on vegetation changes plays a crucial role in the assessment of ecosystem health, monitoring environmental changes, providing early warnings for natural disasters, and supporting decision-making for sustainable development. However, understanding the nonstationary characteristics of drivers affecting vegetation change remains challenging. This study used Enhanced Vegetation Index (EVI) data obtained through Google Earth Engine (GEE), Theil-Sen, and Mann-Kendall methods to analyze the spatial-temporal patterns and trends of vegetation changes in Sichuan, western China from 2000 to 2020. The Geographical and Temporal Weighted Regression (GTWR) method was applied to deal with spatial and temporal nonstationarity simultaneously. Results showed that vegetation cover in Sichuan was good overall, with medium and high vegetation covering more than 78% of the area. About 72.75% of the area showed an increasing trend in vegetation cover, and areas with extremely significant and significant EVI growth (p < 0.01 and 0.01 ≤ p < 0.05) accounted for 23.94% of the total area. The areas with significant increases in vegetation EVI were mainly distributed in northeast, east, southeast, central, and southwest in Sichuan, while the areas with significant decreases were mainly distributed in the central Sichuan plain urban agglomeration and western Sichuan plateau. GTWR addressed the nonstationary effect of the temporal dimension on the drivers of natural and human activities, with a fitted R2 of 0.846. The study identified climate, terrain, and human activities as the primary driving factors behind vegetation EVI fluctuations. Annual average temperature and precipitation, human activities, and slope had a positive impact on vegetation EVI changes, while solar radiation and aspect had a negative inhibitory effect. The effects of climate, terrain, and human activities on EVI changes exhibited significant spatial heterogeneity and clustering, resulting in either positive promotion or negative inhibition. This study provides an additional methodology to solve the nonstationary problem of vegetation change trends and their response mechanisms. The revealed changes in vegetation EVI and the spatiotemporal heterogeneity characteristics of their driving factors are important for fragile ecosystems to adapt to and mitigate the effects of natural changes and human activities. Revealing the variations in vegetation EVI and their underlying drivers can showcase diverse characteristics across regions and time periods, the presence of spatiotemporal heterogeneity holds great significance in comprehending the adaptive strategies employed by fragile ecosystems to mitigate the effects of natural fluctuations and human-induced activities

Quantifying urban expansion and its driving forces in Chengdu, western China

Understanding urban sprawl and its drivers is crucial for sustainable urban development. Most studies on Chinese urbanization have focused on coastal areas, paying little attention to urban centers in western China. This study examines urban expansion based on the Google Earth Engine (GEE), remotely sensed image, urban expansion model, and analysis of buffer and quadrant location in the Geographic Information System (GIS). Additionally, driving forces of urban expansion are examined based on the principle component analysis (PCA). Results indicate that urban land area increased more than 5.60 times, reaching 124,723 ha, an increase of over 400 % during 1990–2020. The urban expansion rate and intensity significantly increased and exhibited spatio-temporal heterogeneity. We identified that urban spatial expansion patterns changed from patch filling to patch border expansion, and urban expansion direction was mainly in the southern, northeastern, southwestern, and northwestern regions, extending along the traffic corridor, ring road, and adjacent cities. We suggest that economic development, population, and urbanization have become the driving factors of urban expansion. The GEE provides a new geographic processing algorithm based on massive image datasets, facilitating remote sensing processing. The results revealed that Chengdu is following trends witnessed in coastal cities of China; however, the significance of various drivers of urban expansion in these cities differs from that of the eastern cities. This study will help formulate policies for better urban land management and sustainable land development

Assessment of Ecological Cumulative Effect due to Mining Disturbance Using Google Earth Engine

Open-pit mining and reclamation damage the land, resulting in unknown and significant changes to the regional ecology and ecosystem services. Surface mining restoration procedures necessitate a significant amount of money, typically at an unclear cost. Due to temporal and regional variability, few studies have focused on the cumulative impacts of mining activities. To investigate the ecological cumulative effects (ECE) of past mining and reclamation activities, this study continuously tracked land cover changes spatially and temporally based on phenological indices and focuses on the spatial and temporal evolution of past mining and reclamation areas using the LandTrendr algorithm. The cumulative trends of ecosystem services in the Pingshuo mining area from 1986 to 2021 were revealed using a uniform standard value equivalent coefficient. Meanwhile, the cumulative ecological effects due to essential ecosystem service functions were analyzed, including soil formation and protection, water containment, biodiversity maintenance, climate regulation, and food production. The synergistic effects and trade-offs among the functions were also explored using Spearman&rsquo;s correlation coefficient. The results showed that (1) open-pit mining resulted in 93.51 km2 of natural land, 39.60 km2 of disturbed land, and 44.58 km2 of reclaimed land in the Pingshuo mine; (2) open-pit mining in the mine mainly resulted in the loss of 122.18 km2 (80.91%) of native grassland, but, through reclamation into grassland (31.30 km2), cropland (72.95 km2), and forest land (10.62 km2), the damaged area caused by mining only slightly increased; (3) the cumulative ecological value of the mining area declined by 128.78 million RMB; however, the real cumulative value per unit area was lower in the disturbance area (1483.47 million RMB) and the reclamation area (1297.00 million RMB) than in the natural area (2120.98 million RMB); (4) the cumulative value of the food production function in the study area increased, although the values of all individual functions in the study area decreased. Most of the cumulative values of services had a strong synergistic relationship. However, in the natural area, food production (FP) showed a trade-off relationship with the cumulative value of biodiversity maintenance (BM), soil formation and protection (SP), and water conservation (WC) service functions, respectively. This study constructed a methodology for analyzing mining-impacted ecosystem services using time-series processes, reproducing historically complete information for policymakers and environmental regulators