A Self-Cascade Oxygen-Generating Nanomedicine for Multimodal Tumor Therapy.

Natural and artificial enzyme oxygen-generating systems for photodynamic therapy (PDT) are developed for tumor treatment, yet they have fallen short of the desired efficacy. Moreover, both the enzymes and photosensitizers usually need carriers for efficient delivery to tumor sites. Here, a self-cascade-enhanced multimodal tumor therapy is developed by ingeniously integrating self-cascade-enhanced PDT with Zn2+-overloading therapy. Manganese-porphyrin (TCPP-Mn) is chosen both as the photosensitizer and catalase (CAT) mimic, which can be encapsulated within glucose oxidase (GOx). Acid-responsive zeolitic imidazolate framework-8 (ZIF-8) is applied as the carrier for TCPP-Mn@GOx (T@G), attaining TCPP-Mn@GOx@ZIF-8 (T@G@Z). T@G@Z demonstrates robust anti-tumor ability as follows: upon the structural degradation of ZIF-8, GOx can mediate the oxidation of glucose and generate hydrogen peroxide (H2O2); TCPP-Mn can catalyze H2O2 into O2 for self-cascade-enhanced PDT; meanwhile, the released Zn2+ can enhance oxidative stress and induce mitochondrial dysfunction by destroying mitochondrial membrane potential; furthermore, immunotherapy can be activated to resist primary tumor and tumor metastasis. The self-cascade-enhanced T@G@Z exhibited its potential application for further tumor management.

Evaluating multifaceted effects of watershed properties and human activities on drought propagation in the Wei River Basin with an integrated framework.

Understanding the factors driving propagation from meteorological to hydrological drought is crucial for drought mitigation. In this study, an integrated framework based on the Soil and Water Assessment Tool model, standardised drought indices and Geographical Detector were used to investigate how and to what extent watershed properties and human activities affect the spatial heterogeneity of drought propagation in the Wei River Basin, a typical arid and semi-arid region in China. Results indicated that (1) spatially, the propagation times increased from southwest to northeast. Seasonally, the propagation was shorter and stronger in summer and autumn. (2) The aridity index significantly affected the spatial distribution of drought propagation time for the entire basin, especially in summer, while human activities primarily drove spatial distribution in the sub-basins. The explanatory power of any two independent factors was non-linearly enhanced after the interaction. (3) Watershed properties potentially impacted the anthropogenic driving factor of drought propagation. Strong anthropogenic effects on drought propagation often occurred in watersheds with moderate drought levels, steep slopes, low elevations, and small areas, and the key factors varied seasonally. These findings help elucidate the multifaceted effects of watershed properties and human activities on drought propagation. The proposed framework and the results of this study provide valuable guidance for formulating precise drought control strategies in the Wei River Basin and worldwide.

The competition of heavy metals between hyporheic sediments and microplastics of driving factors in the Beiluo River Basin.

Both sediments and microplastics (MPs) are medias of heavy metals (HMs) in river ecosystems. This study investigated HMs (Mn, Cr, V, As, Cu, Co, Cd, Pb, and Ni) concentration and driving factors for competitive enrichment between hyporheic sediments versus MPs. The medias basic characteristics indicated that the sediments were mostly sand and rich in Fe2O3; three polymer types were identified, with blue, fragment, less than 500 µm being the main types of MPs. The results have shown that the average content of extracted HMs in MPs was much higher than that of the same metals accumulated in sediments. HMs in sediments and MPs reached heavily polluted at some points, among which As and Cd were ecological risks. Electrostatic adsorption and surface complexation, and biofilm-mediated and organic matter complexation were the interaction mechanism of HMs with sediments and MPs. Further, the driving factors affecting the distribution of HMs in the two carriers were analyzed by multivariate statistical analysis. The results demonstrated that carrier characteristics, hydrochemical factors, and the inherent metal load of MPs were the main causes of the high HMs content. These findings improved our understanding of HMs fate and environmental risks across multiple medias.

Famine exposure in early life increases risk of cataracts in elderly stage.

Background: Epidemiological studies have shown that early-life nutritional deficiencies are associated with an increased risk of diseases later in life. This study aimed to explore the correlation between famine exposure during the early stages of life and cataracts. Methods: We included 5,931 participants from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2018 cross-sectional data in our study. Subjects were categorized into three groups by their age during the famine: adulthood group, school age famine exposure group, and teenage famine exposure group. Utilizing binary logistic regression models, we investigated the relationship between early-life famine exposure and cataracts. Results: Compared to the adulthood group, both the school age exposure group (OR = 2.49, 95%CI = 1.89-3.27) and teenage exposure group (OR = 1.45, 95%CI = 1.20-1.76) had a heightened risk of developing cataracts in elderly stage. And the sex differences in the impact of famine during early years on elderly cataract risk were observed, particularly indicating a higher risk among women who experienced childhood famine compared to men with similar exposure. Conclusion: Famine exposure during the early stages of life is associated with a heightened risk of developing cataracts in old age. To prevent cataracts in elderly individuals, particularly in females, measures should be taken to address nutritional deficiencies in these specific periods.

Measurement of the burdens of neonatal disorders in 204 countries, 1990-2019: a global burden of disease-based study.

Background: Neonatal disorders are facing serious public health challenges. Previous studies were based on limited data sources and had a narrow geographical scope. We aim to understand the trends of alteration in the burden of neonatal disorders from 1990 to 2019 in 204 countries and territories. Methods: Data were investigated from the Global Burden of Disease Study 2019. First, we visualized the burden of neonatal disorders using the number of cases and the age-standardized incidence rate (ASIR), death rate (ASDR), and disability-adjusted life years (ASR-DALYs) from 1990 to 2019. Second, estimated annual percentage changes (EAPCs) were used to evaluate the temporal trends of disease burden during different periods. Finally, the sociodemographic index (SDI) and human development index (HDI) were used to determine whether there exists a correlation between socioeconomic development level, human development level, and potential burden consequences. Results: Overall, in the past 30 years, the ASIR trends have remained relatively steady, whereas the ASDR and ASR-DALYs have declined. However, the burden of neonatal disorders varied greatly in various regions and countries. Among 21 regions, the ASIR trend had the largest increase in Central Latin America (EAPC = 0.42, 95%CI = 0.33-0.50). Conversely, the ASDR and ASR-DALYs experienced the largest decrease in Central Europe (EAPC = -5.10, 95%CI = -5.28 to 4.93) and East Asia (EAPC = -4.07, 95%CI = -4.41 to 3.73), respectively. Among 204 countries, the ASIR (EAPC = 3.35, 95%CI = 3.13-3.56) trend in Greece displayed the most significant increase, while the ASDR (EAPC = 1.26, 95%CI = 1.01-1.50) and ASR-DALYs (EAPC = 1.26, 95%CI = 1.03-1.49) trends in Dominica experienced the most substantial increase. Furthermore, there was a strong correlation between the EAPCs in ASIR, ASDR, ASR-DALYs, and SDI or HDI in 2019, with some exceptions. In addition, countries with elevated levels of HDI experienced a faster increase in ASDR and ASR-DALYs for neonatal disorders. Conclusion: Although the burden of neonatal disorders shows a downward trend from 1990 to 2019, it is still not optimistic. It is necessary to implement a multi-pronged approach to reduce the increasing burden of neonatal disorders.

Reactive Oxygen Species- and Cell-Free DNA-Scavenging Mn3O4 Nanozymes for Acute Kidney Injury Therapy.

Reactive oxygen species (ROS) scavenging therapy toward acute kidney injury (AKI) is promising, but no effective ROS scavenging drug has been developed yet. Moreover, cell-free DNA (cfDNA) is also involved in AKI, but the corresponding therapies have not been well developed. To tackle these challenges, Mn3O4 nanoflowers (Nfs) possessing both ROS and cfDNA scavenging activities were developed for better AKI protection as follows. First, Mn3O4 Nfs could protect HK2 cells through cascade ROS scavenging (dismutating ·O2- into H2O2 by superoxide dismutase-like activity and then decomposing H2O2 by catalase-like activity). Second, Mn3O4 Nfs could efficiently adsorb cfDNA and then decrease the inflammation caused by cfDNA. Combined, remarkable therapeutic efficacy was achieved in both cisplatin-induced and ischemia-reperfusion AKI murine models. Furthermore, Mn3O4 Nfs could be used for the T1-MRI real-time imaging of AKI. This study not only offered a promising treatment for AKI but also showed the translational potential of nanozymes.