Search

Efficientdelivery of therapeutic agents with nanocarriers intothe nucleus to achieve high therapeutic efficiency is still a majorchallenge for cancer therapy due to mucosal barriers, nonspecificuptake, and intracellular drug resistance. In this study, we developa dual-responsive polymer micelle system with sheddable polyethylenimine(PEI) shells for actively targeted drug delivery. This system exhibitsan ultrasensitive negative-to-positive charge reversal in responseto the extracellular pH value, resulting in greatly enhanced uptakeby cancer cells via electrostatic interaction. Moreover, the activetargeting ability can further promote the selective uptake of thenanocarriers in the cancer cell. Once the micelles escape from thelysosomes, the disulfide linkages can be cleaved by GSH in the cytoplasm,and in turn the hydrophilic PEI shell is deshielded, leading to therapid release of the encapsulated agent into the nuclei. The antitumoractivity in 4T1 tumor-bearing mice reveals that this novel systempossesses a long blood circulation due to the originally negativelycharged surface and can significantly promote the cell internalizationand intracellular drug release, thus leading to a high therapeuticefficacy against resistant tumors and fewer side effects to normaltissues. [ABSTRACT FROM AUTHOR]

Background: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden., Methods: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status., Results: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status., Conclusions: Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.

Objective: To investigate the current situation and related factors of adults environmental health knowledge-attitude-practice(KAP)in four cities., Methods: From March to April 2021, 1252 permanent residents in Mianyang City, Ya'an City in Sichuan Province, Suzhou City and Yangzhou City in Jiangsu Province were investigated on environmental health KAP by using a self-made electronic questionnaire. Analysis of variance, multiple linear regression and Person rank correlation were used to analyze the difference of public environmental KAP level, related factors, and the correlation of knowledge, attitude and behavior scores., Results: There were significant differences in the level of environmental health KAP among people in different cities(F=47.632, P<0.001), age group(F=34.676, P<0.001), education level(F=49.574, P<0.001), BMI(F=4.560, P=0.003), total annual family income(F=27.977, P<0.001), smoking status(t=11.121, P=0.001)and ways of ingesting environmental health knowledge(F=88.405, P<0.001), and except BMI, other items were the related factors of environmental health KAP. The score of environmental health attitude was higher than that of behavior and knowledge(F=154.34, P<0.001). The scores of knowledge and behavior, knowledge and attitude, attitude and behavior were correlated, and the correlation coefficients were 0.667, 0.414 and 0.450 respectively(P<0.01)., Conclusion: The number of ways to acquire environmental health knowledge, total annual family income, education level, age and smoking status are all related factors of the adults environmental knowledge-attitude-practice level in four cities in 2021.

Introduction: Renal ischemia-reperfusion injury (IRI) is one of the major causes of acute kidney injury, and its mechanism is complex involving multiple factors, while delayed ischemic preconditioning (DIPC) has a protective effect on the above process. In our previous study, we found that DIPC can exert its protection on renal IRI by inhibiting the maturation of dendritic cells (DCs), but the mechanism has not been clarified. This study aimed to investigate the protective mechanism of DIPC on renal IRI in mice through Treg mediated by immature DCs (imDCs)., Methods: The IRI mice model, DIPC treatment, and conditional CD11c + DCs (CD11c-DTR) knockout mice were used to perform our study. The maturation and differentiation of DCs and Treg cells in the kidney and spleen were analyzed by flow cytometry. HE staining was used to evaluate the pathology of the kidney tissue. The level of creatinine (Cr), oxidative stress factors (SOD, MDA), and inflammatory factors (TNF-α, IL-10, IL-4) were also measured. Then, imDCs were co-cultured with HK-2 cells, and apoptosis was analyzed with flow cytometry and PI-Hoechst 33,342 fluorescence staining to assess the apoptosis rate of HK-2 cells under hypoxic-reoxygenated (H/R) conditions., Results: DIPC could decrease renal Cr levels, alleviate pathological renal damage, and reduce oxidative stress and inflammation caused by IRI. Moreover, DIPC could decrease the number of mature DCs (mDCs) and increase Treg lymphocyte infiltration in the kidney tissue, while the reduction of DCs reversed this process. In addition, our in vitro experiment found that in the H/R model, the apoptosis of HK-2 cells decreased which were co-cultured with imDCs., Conclusion: DIPC can regulate the differentiation of DCs into imDCs, thus affecting the differentiation level and distribution of Treg cells to exert its protective effect on renal IRI., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)