An intelligent Cu/ZIF-8-based nanodrug delivery system for tumor-specific and synergistic therapy via tumor microenvironment-responsive cascade reaction.

An intelligent nanodrug delivery system (Cu/ZIF-8@GOx-DOX@HA, hereafter CZGDH) consisting of Cu-doped zeolite imidazolate framework-8 (Cu/ZIF-8, hereafter CZ), glucose oxidase (GOx), doxorubicin (DOX), and hyaluronic acid (HA) was established for targeted drug delivery and synergistic therapy of tumors. The CZGDH specifically entered tumor cells through the targeting effect of HA and exhibited acidity-triggered biodegradation for subsequent release of GOx, DOX, and Cu2+ in the tumor microenvironment (TME). The GOx oxidized the glucose (Glu) in tumor cells to produce H2O2 and gluconic acid for starvation therapy (ST). The DOX entered the intratumoral cell nucleus for chemotherapy (CT). The released Cu2+ consumed the overexpressed glutathione (GSH) in tumor cells to produce Cu+. The generated Cu+ and H2O2 triggered the Fenton-like reaction to generate toxic hydroxyl radicals (·OH), which disrupted the redox balance of tumor cells and effectively killed tumor cells for chemodynamic therapy (CDT). Therefore, synergistic multimodal tumor treatment via TME-activated cascade reaction was achieved. The nanodrug delivery system has a high drug loading rate (48.3 wt%), and the three-mode synergistic therapy has a strong killing effect on tumor cells (67.45%).

The impact of risk perception and institutional trust on COVID-19 vaccine hesitancy in China.

Vaccination has become the primary means for citizens to prevent severe morbidity and mortality during the pandemic. However, vaccine hesitancy poses a major threat to global public health security. Based on the data from Chinese General Social Survey in 2021, this study aims to explore the socio-political aspects of COVID-19 vaccine hesitancy, focusing on the relationship between COVID-19 risk perceptions, institutional trust and vaccine hesitancy. Among the samples, 39.8% of the respondents exhibited COVID-19 vaccine hesitancy, 48.9% had a high awareness of the risk of COVID-19, and 74.6% presented a high level of trust in institutions. The results showed that higher risk perception and institutional trust are negatively correlated with vaccine hesitancy (p < .001). Institutional trust had no statistically significant moderating effect on the association between risk perception and vaccine hesitancy, but the role of institutional trust in influencing vaccine hesitancy is more significant at a lower level of perceptions of COVID-19 risk. Furthermore, regional variations in the factors contributing to vaccine hesitancy were demonstrated in China. These findings have important implications for developing strategies to address vaccine hesitancy.

Emergence of decadal linkage between Western Australian coast and Western-central tropical Pacific.

The impact of interbasin linkage on the weather/climate and ecosystems is significantly broader and profounder than that of only appearing in an individual basin. Here, we reveal that a decadal linkage of sea surface temperature (SST) has emerged between western Australian coast and western-central tropical Pacific since 1985, associated with continuous intensification of decadal variabilities (8-16 years). The rapid SST changes in both tropical Indian Ocean and Indo-Pacific warm pool in association to greenhouse gases and volcanoes are emerging factors resulting in enhanced decadal co-variabilities between these two regions since 1985. These SST changes induce enhanced convection variability over the Maritime Continent, leading to stronger easterlies in the western-central tropical Pacific during the warm phase off western Australian coast. The above changes bring about cooling in the western-central tropical Pacific and strengthened Leeuwin Current and anomalous cyclonic wind off western Australian coast, and ultimately resulting in enhanced coupling between these two regions. Our results suggest that enhanced decadal interbasin connections can offer further understanding of decadal changes under future warmer conditions.