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The RAS gene family holds a central position in controlling key cellular activities such as migration, survival, metabolism, and other vital biological processes. The activation of RAS signaling cascades is instrumental in the development of various cancers. Although several RAS inhibitors have gained approval from the US Food and Drug Administration for their substantial antitumor effects, their widespread and severe adverse reactions significantly curtail their practical usage in the clinic. Thus, there exists a pressing need for a comprehensive understanding of these adverse events, ensuring the clinical safety of RAS inhibitors through the establishment of precise management guidelines, suitable intermittent dosing schedules, and innovative combination regimens. This review centers on the evolution of RAS inhibitors in cancer therapy, delving into the common adverse effects associated with these inhibitors, their underlying mechanisms, and the potential strategies for mitigation. [ABSTRACT FROM AUTHOR]

Regorafenib, an oral multikinase inhibitor of angiogenic, stromal, and oncogenic receptor tyrosine kinases, has been approved for the treatment of metastatic colorectal cancer, gastrointestinal stromal tumors, and hepatocellular carcinoma by the US Food and Drug Administration and European Medicines Agency. However, regorafenib-induced cardiotoxicity increases the risk of mortality. Despite reports that regorafenib can cause mitochondrial dysfunction in cardiomyocytes, the molecular mechanism of regorafenib-induced cardiotoxicity is much less known and there is an urgent need for intervention strategies. Here, we treated mice with vehicle or 200 mg/kg regorafenib daily for 42 d by gavage or treated cardiomyocyte lines with 8, 16, or 32 μM regorafenib, and we found that regorafenib could cause apoptosis, mitochondrial injury, and DNA damage in cardiomyocytes. Mechanistically, regorafenib can reduce the expression of EPHA2, which inhibits AKT signaling, leading to cardiomyocyte apoptosis and cardiotoxicity. In addition, we showed that recovering EPHA2 expression via plasmid-induced overexpression of EPHA2 or schisandrin C, a natural product, could prevent regorafenib-induced cardiotoxicity. These findings demonstrated that regorafenib causes cardiomyocyte apoptosis and cardiac injury by reducing the expression of EPHA2 and schisandrin C could prevent regorafenib-induced cardiotoxicity by recovering EPHA2 expression, which provides a potential management strategy for regorafenib-induced cardiotoxicity and will benefit the safe application of regorafenib in clinic. [ABSTRACT FROM AUTHOR]

Oases play a crucial role in arid regions within the human–environmental system, holding significant ecological and biological importance. The Oasis Cold Island Effect (OCIE) represents a distinct climatic feature of oases and serves as a vital metric for assessing oasis ecosystems. Previous studies have overlooked the spatial extent of the Oasis Cold Island Effect (OCIE), specifically the boundary delineating areas influenced and unaffected by oases. This boundary is defined as the Oasis Cold Island Footprint (OCI FP). Utilizing Logistic modeling and MODIS data products, OCI FPs were calculated for the Ejina Oasis from 2000 to 2019. The assessment results underscore the accuracy and feasibility of the methodology, indicating its potential applicability to other oases. Spatial and temporal distributions of OCI FPs and the intensity of the Oasis Cold Island Effect Intensity (OCIEI) in the Ejina Oasis were analyzed, yielding the following findings: (1) OCI FP area and complexity were smallest in summer and largest in autumn. (2) Over the period 2000–2019, OCI FPs exhibited a pattern of increase, decrease, and subsequent increase. (3) OCIEI peaks in summer and reaches its lowest point in winter. Lastly, the study addresses current limitations and outlines future research objectives. [ABSTRACT FROM AUTHOR]