CRISPR accelerates the cancer drug discovery

Emerging cohorts and basic studies have associated certain genetic modifications in cancer patients, such as gene mutation, amplification, or deletion, with the overall survival prognosis, underscoring patients??? genetic background may directly regulate drug sensitivity/resistance during chemotherapies. Understanding the molecular mechanism underpinning drug sensitivity/resistance and further uncovering the effective drugs have been the major ambition in the cancer drug discovery. The emergence and popularity of CRISPR/Cas9 technology have reformed the entire life science research, providing a precise and simplified genome editing tool with unlimited editing possibilities. Furthermore, it presents a powerful tool in cancer drug discovery, which hopefully facilitates us with a rapid and reliable manner in developing novel therapies and understanding the molecular mechanisms of drug sensitivity/resistance. Herein, we summarized the application of CRISPR/Cas9 in drug screening, with the focus on CRISPR/Cas9 mediated gene knockout, gene knock-in, as well as transcriptional modification. Additionally, this review provides the concerns, cautions, and ethnic considerations that need to be taken when applying CRISPR in the drug discovery.Peer reviewe

Transformation of animal utilization strategies from the late Neolithic to the Han Dynasty in the Hexi Corridor, northwest China: Zooarchaeological and stable isotopic evidence

The trajectory and influencing factors for changes to ancient human livelihoods in the Hexi Corridor of northwest China have been intensively discussed. The Hexi Corridor is a key crossroads for trans-Eurasian exchange in both the prehistoric and historical periods. Although most studies have focused on the reconstruction of human paleodiet and plant subsistence, the diachronic change of animal utilization strategies spanning the prehistoric and historical periods remains unclear, due to the absence of zooarchaeological and isotopic studies, especially in Han Dynasty (202 BCE–220 CE). Here we report new zooarchaeological, stable isotope, and radiocarbon dating data from the Heishuiguo Cemetery of the Han Dynasty in the Hexi Corridor, indicating that humans mainly used domestic chickens, pigs and sheep as funerary objects, with other buried livestock including cattle, horses and dogs. Stable carbon and nitrogen isotope data suggest humans might have fed chickens, pigs and dogs more C4 foods (likely millets or their byproducts) than herbivorous livestock in the Heishuiguo during the Han Dynasty. Compared to other prehistoric zooarchaeological and isotopic studies in the Hexi Corridor, we detected an increasing significance of herbivorous livestock in animal utilization strategies compared with omnivorous livestock, and a basic declining weight of C4 foods in fodders from ∼2,300 to 200 BCE, which was probably induced by long-distance exchange and climate fluctuation. However, the trend was reversed during the Han Dynasty in the Hexi Corridor, primarily due to the control of the area by the Han Empire and the subsequent massive immigration from the Yellow River valley of north China

Analysis of Active Components in Salvia Miltiorrhiza Injection Based on Vascular Endothelial Cell Protection

Correlation analysis based on chromatograms and pharmacological activities is essential for understanding the effective components in complex herbal medicines. In this report, HPLC and measurement of antioxidant properties were used to describe the active ingredients of Salvia miltiorrhiza injection (SMI). HPLC results showed that tanshinol, protocatechuic aldehyde, rosmarinic acid, salvianolic acid B, protocatechuic acid and their metabolites in rat serum may contribute to the efficacy of SMI. Assessment of antioxidant properties indicated that differences in the composition of serum powder of SMI caused differences in vascular endothelial cell protection. When bivariate correlation was carried out it was found that salvianolic acid B, tanshinol and protocatechuic aldehyde were active components of SMI because they were correlated to antioxidant properties

Multi-Timescale Analysis of the Evolution of Sandy Coastline: A Case Study in South China

The coastal zone is essential to economic and social development. However, coastline evolution is a complex research topic, owing to the intersection and coupling of different fields such as wind, wave, and current. Research is further complicated by variations in these fields’ temporal and spatial scales. This study acquired and preprocessed multi-phase Landsat remote sensing satellite images of the eastern coast, from Wailuo to Zhuzi, from 1987 to 2021. Then, the decoded and extracted instantaneous coastline images were corrected, and quantitative analysis was carried out through the Digital Coastline Analysis System (DSAS). The results showed that trends of coastline evolution in the study area in the medium–long term were overall balanced. All the transects manifested temporal and spatial differences, and erosional hot spots were mainly concentrated on the coastal cape and its vicinity. To investigate storm-induced beach erosion in the short term, the 400 m coastline of Baimao in the area was selected as a field site, and the field survey was conducted during two storms. The distribution of the dynamic parameters of sediment deposition was also investigated. The results showed that the beach in the field site had an excellent ability to resist storm erosion and that the topographic change was greatly affected by geological conditions in the area, such as reef masking and a typical headland beach. The grain size parameters of the beach sediments were sensitive to storms, reflecting the adjustment of the beach surface during typhoons. This study shows how a multi-timescale analysis could represent an efficient approach to understanding the dynamic evolution of the coastline. It showed a detailed description of the historical coastline evolution of the eastern coast of the Leizhou Peninsula after 1987. Additionally, the coastline evolution and sediment distribution for the sedimentation dynamic environment of Baimao tourist area in the short term were also investigated. In conclusion, this study can contribute to the rational utilization of coastal resources, to coastal disaster prevention, and the mitigation of local coastal areas

Profiles and Risk Assessment of Organochlorine Pesticides in Three Gorges Reservoir, China

The environmental pollution of the Three Gorges Reservoir in China may not be desirable and has adverse effects on biodiversity and human health in this region. Concentrations of 16 organochlorine pesticides (OCPs) were investigated in 19 surface water samples collected from near dam region of the Three Gorges Reservoir. The concentrations of total OCPs ranged from 14 to 88 ng L-1 with a geometric mean of 23 ng L-1. The spatial distribution of OCPs concentrations indicated the giant reservoir was sink of OCPs for upstream as well as source for downstream. The mean concentrations of total hexachlorocyclohexanes (HCHs) and dichlorodiphenyltrichloroethanes (DDTs) were 10 and 9.7 ng L (1), respectively. Historical use of lindane and DDT was found to be the primary source of HCHs and DDTs. The ratio between heptachlor and its metabolic products indicated new input of heptachlor occurred in this region. Among the 16 detected OCPs, the cancer risks for human of heptachlor and heptachlorepoxide were all above 10(-4), indicating a potential threat of the two OCPs to human health