The impact of sex in the development of long-term toxicities affecting the quality of life of cancer survivors has not been investigated experimentally. To address this issue, a series of neurologic and cardiologic endpoints were used to investigate sex-based differences triggered by paclitaxel treatment and radiotherapy exposure. Male and female WT mice were treated with Paclitaxel (150 and 300 mg/kg) administered weekly over 6 weeks or exposed to 19 Gy cardiac irradiation. Cohorts were analyzed for behavioral and neurobiologic endpoints to assess systemic toxicity of paclitaxel or cardiovascular endpoints to assess radiotherapy toxicity. Interestingly, female WT mice exhibited enhanced tolerance compared to male WT mice regardless of the treatment regimen. To provide insight into the possible sex-specific protective mechanisms, rhoB deficient animals and elderly mice (22 months) were used with a focus on the possible contribution of sex hormones including estrogen. RhoB deficiency and advanced age had no impact on neurocognitive impairment induced by Paclitaxel but reversed the cardioprotection was observed in females after radiotherapy. Conversely, rhoB deficiency protected males from radiation toxicity. In sum, rhoB was identified as a molecular determinant driving estrogen dependent cardioprotection in female mice, whereas neuroprotection was not sex-hormone dependent. To our knowledge, this study revealed for the first time sex- and organ-specific responses to paclitaxel and radiotherapy.

The Pearl River Delta (PRD) has undergone complex geological development within a multi-island faulted basin, shaped by the interplay of regional tectonic movements, Quaternary sea-level fluctuations, and fluvial-marine interactions. Despite a great number of studies on the Holocene sedimentary sequences and spatial difference of lithofacies and environments, scant attention has been paid to the overarching human influence on deltaic evolution and coastline modifications since the Neolithic epoch. To further elucidate the spatial variation in Holocene sedimentation and its underlying basement topography shaped during the Last Glacial Maximum (LGM), we compiled a comprehensive dataset incorporating borehole data from over 2,800 cores within the PRD. Subsequently, high-resolution isobath maps of Quaternary deltaic deposits were generated, offering unprecedented insights into sediment distribution. This dataset facilitated a nuanced reconstruction of pre-Holocene topography, revealing a zone characterized by elongated, deep-incised valleys governed by NW-SE fault orientations. Further, we delineated coastline shifts since the period of maximum marine transgression (~7000 years BP), contributing to an enhanced understanding of the formation and evolutionary patterns of the delta and the river network oscillations. Our findings illuminate increasing anthropogenic impact on the rate of fluvial sedimentation and land growth, particularly accentuated over the last two millennia, favoring deltaic accretion. The current study has considerable implications for understanding the dynamic interplay between land-sea interactions and anthropogenic activities in shaping the delta, and stands to significantly inform land and resource management strategies, as well as future urban planning within the delta's bay areas.