Cancer Stem Cells — Perspectives and How to Target Them

Cancer stem cell is a progressive concept moving forward to interpret the hard-to-cure nature of cancer and the relevant behavior in response to clinical therapies. Despite the remaining debates regarding the existence of cancer stem cells, the cancer stem cell model provides a potential approach for advanced innovative therapies targeting the “roots” of cancer, which has enhanced treatment outcomes. This chapter summarizes advanced perspectives in the field of cancer stem cell research, including experimental strategies for targeting these cells, highlights challenges of this theory, and explores feasible therapeutic strategies for overcoming the intrinsic resistance of cancer stem cells to clinical treatment

Spatiotemporal Variations of Dryland Vegetation Phenology Revealed by Satellite-Observed Fluorescence and Greenness across the North Australian Tropical Transect

Accurate characterization of spatial patterns and temporal variations in dryland vegetation is of great importance for improving our understanding of terrestrial ecosystem functioning under changing climates. Here, we explored the spatiotemporal variability of dryland vegetation phenology using satellite-observed Solar-Induced chlorophyll Fluorescence (SIF) and the Enhanced Vegetation Index (EVI) along the North Australian Tropical Transect (NATT). Substantial impacts of extreme drought and intense wetness on the phenology and productivity of dryland vegetation are observed by both SIF and EVI, especially in the arid/semiarid interior of Australia without detectable seasonality in the dry year of 2018–2019. The greenness-based vegetation index (EVI) can more accurately capture the seasonal and interannual variation in vegetation production than SIF (EVI r2: 0.47~0.86, SIF r2: 0.47~0.78). However, during the brown-down periods, the rate of decline in EVI is evidently slower than that in SIF and in situ measurement of gross primary productivity (GPP), due partially to the advanced seasonality of absorbed photosynthetically active radiation. Over 70% of the variability of EVI (except for Hummock grasslands) and 40% of the variability of SIF (except for shrublands) can be explained by the water-related drivers (rainfall and soil moisture). By contrast, air temperature contributed to 25~40% of the variability of the effective fluorescence yield (SIFyield) across all biomes. In spite of high retrieval noises and variable accuracy in phenological metrics (MAE: 8~60 days), spaceborne SIF observations, offsetting the drawbacks of greenness-based phenology products with a potentially lagged end of the season, have the promising capability of mapping and characterizing the spatiotemporal dynamics of dryland vegetation phenology

A UPLC-MS/MS method for simultaneous determination of tiamulin and its metabolites in Crucian carp (Carassius carassius): an in vivo metabolism and tissue distribution study

Tiamulin (TML) has been studied and analyzed in pigs, cattle, chickens, ducks, and other domestic animals, however, its metabolic state in fish has not been well explored. This study investigated TML metabolism in Crucian carp (Carassius carassius). After intraperitoneal injection of TML into Crucian carp, ultra-high performance liquid chromatography with quadrupole and time-of-flight mass spectrometry (UPLC/Q-TOF MS) analysis, was conducted to identify TML metabolites. The UPLC/Q-TOF MS analysis and the relative molecular mass of the metabolites obtained from related literature identified five metabolites in Crucian carp. These metabolites were M1 (510.2908, C28H48NO5S+), M2 (510.2908, C28H48NO5S+), M3 (466.2750, C26H44NO4S+), M4 (482.2663, C26H44NO5S+), and M5 (482.2663, C26H44NO5S+). The enrichment and metabolism of TML and its metabolites in Crucian carp were investigated using the drug bath method combined with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). TML exhibited an overall trend of an initial increase followed by a decrease. Moreover, the drug enrichment rate was fast and reached saturation after two days. The bioconcentration factor of TML in Crucian carp was 3.01. However, the drug had a slow elimination rate, with its complete metabolism occurring after 20 days

Assessing the impact of extreme droughts on dryland vegetation by multi-satellite solar-induced chlorophyll fluorescence

Satellite-estimated solar-induced chlorophyll fluorescence (SIF) is proven to be an effective indicator for dynamic drought monitoring, while the capability of SIF to assess the variability of dryland vegetation under water and heat stress remains challenging. This study presents an analysis of the responses of dryland vegetation to the worst extreme drought over the past two decades in Australia, using multi-source spaceborne SIF derived from the Global Ozone Monitoring Experiment-2 (GOME-2) and TROPOspheric Monitoring Instrument (TROPOMI). Vegetation functioning was substantially constrained by this extreme event, especially in the interior of Australia, in which there was hardly seasonal growth detected by neither satellite-based observations nor tower-based flux measurements. At a 16-day interval, both SIF and enhanced vegetation index (EVI) can timely capture the reduction at the onset of drought over dryland ecosystems. The results demonstrate that satellite-observed SIF has the potential for characterizing and monitoring the spatiotemporal dynamics of drought over water-limited ecosystems, despite coarse spatial resolution coupled with high-retrieval noise as compared with EVI. Furthermore, our study highlights that SIF retrieved from TROPOMI featuring substantially enhanced spatiotemporal resolution has the promising capability for accurately tracking the drought-induced variation of heterogeneous dryland vegetation

Latest Study on the Relationship between Pathological Process of Inflammatory Injury and the Syndrome of Spleen Deficiency and Fluid Retention in Alzheimer’s Disease

Inflammation exists throughout the incidence and progression of Alzheimer’s disease (AD). Traditional Chinese medicine (TCM) differentiates the pathogenesis of AD as kidney essence deficiency and qi and blood deficiency as well as blood stasis in syndromes, whose action mechanisms are all associated with the intervention in its inflammatory process. Our preliminary studies both in clinic and in vitro have demonstrated that the syndrome of spleen deficiency and fluid retention has also been an important pathogenesis for the incidence and development of AD. Hence, the paper aims to further illustrate the correlation between inflammatory process in AD and the syndrome of spleen deficiency and fluid retention, laying solid foundation for the application of invigorating the spleen and eliminating the dampness in clinic, and enriching the theoretical connotation for AD prevention and treatment in TCM

A novel lytic phage potentially effective for phage therapy against Burkholderia pseudomallei in the tropics.

BACKGROUND: Burkholderia pseudomallei is a tropical pathogen that causes melioidosis. Its intrinsic drug-resistance is a leading cause of treatment failure, and the few available antibiotics require prolonged use to be effective. This study aimed to assess the clinical potential of B. pseudomallei phages isolated from Hainan, China. METHODS: Burkholderia pseudomallei strain (HNBP001) was used as the isolation host, and phages were recovered from domestic environmental sources, which were submitted to the host range determination, lytic property assays, and stability tests. The best candidate was examined via the transmission electron microscope for classification. With its genome sequenced and analyzed, its protective efficacy against B. pseudomallei infection in A549 cells and Caenorhabditis elegans was evaluated, in which cell viability and survival rates were compared using the one-way ANOVA method and the log-rank test. RESULTS: A phage able to lyse 24/25 clinical isolates was recovered. It was classified in the Podoviridae family and was found to be amenable to propagation. Under the optimal multiplicity of infection (MOI) of 0.1, an eclipse period of around 20 min and a high titer (1012 PFU/ml) produced within 1 h were demonstrated. This phage was found stabile at a wide range of temperatures (24, 37, 40, 50, and 60 °C) and pH values (3-12). After being designated as vB_BpP_HN01, it was fully sequenced, and the 71,398 bp linear genome, containing 93 open reading frames and a tRNA-Asn, displayed a low sequence similarity with known viruses. Additionally, protective effects of applications of vB_BpP_HN01 (MOI = 0.1 and MOI = 1) alone or in combination with antibiotics were found to improve viability of infected cells (70.6 ± 6.8%, 85.8 ± 5.7%, 91.9 ± 1.8%, and 96.8 ± 1.8%, respectively). A significantly reduced mortality (10%) and a decreased pathogen load were demonstrated in infected C. elegans following the addition of this phage. CONCLUSIONS: As the first B. pseudomallei phage was isolated in Hainan, China, phage vB_BpP_HN01 was characterized by promising lytic property, stability, and efficiency of bacterial elimination during the in vitro/vivo experiments. Therefore, we can conclude that it is a potential alternative agent for combating melioidosis

On the Use of NLDAS2 Weather Data for Hydrologic Modeling in the Upper Mississippi River Basin

Weather data are the key forces that drive hydrological processes so that their accuracy in watershed modeling is fundamentally important. For large-scale watershed modeling, weather data are either generated by using interpolation methods or derived from assimilated datasets. In the present study, we compared model performances of the Soil and Water Assessment Tool (SWAT), as driven by interpolation weather data, and NASA North American Land Data Assimilation System Phase Two (NLDAS2) weather dataset in the Upper Mississippi River Basin (UMRB). The SWAT model fed with different weather datasets were used to simulate monthly stream flow at 11 United States Geological Survey (USGS) monitoring stations in the UMRB. Model performances were evaluated based on three metrics: coefficient of determination (R2), Nash−Sutcliffe coefficient (NS), and percent bias (Pbias). The results show that, after calibration, the SWAT model compared well at all monitoring stations for monthly stream flow using different weather datasets indicating that the SWAT model can adequately produce long-term water yield in UMRB. The results also show that using NLDAS2 weather dataset can improve SWAT prediction of monthly stream flow with less prediction uncertainty in the UMRB. We concluded that NLDAS2 dataset could be used by the SWAT model for large-scale watersheds like UMRB as a surrogate of the interpolation weather data. Further analyses results show that NLDAS2 daily solar radiation data was about 2.5 MJ m−2 higher than the interpolation data. As such, the SWAT model driven by NLDAS2 dataset tended to underestimate stream flow in the UMRB due to the overestimation in evapotranspiration in uncalibrated conditions. Thus, the implication of overestimated solar radiation by NLDAS2 dataset should be considered before using NLDAS2 dataset to drive the hydrological model