Exosomes Derived from Mouse Breast Carcinoma Cells Facilitate Diabetic Wound Healing.

BACKGROUND: Exosomes derived from breast cancer have been reported to play a role in promoting cell proliferation, migration, and angiogenesis, which has the potential to accelerate the healing process of diabetic wounds. The aim of this investigation was to examine the function of exosomes originating from 4T1 mouse breast carcinoma cells (TEXs) in the process of diabetic wound healing. METHODS: The assessment of primary mouse skin fibroblasts cell proliferation and migration was conducted through the utilization of CCK-8 and wound healing assays, while the tube formation of HUVECs was evaluated by tube formation assay. High-throughput sequencing, RT-qPCR and cell experiments were used to detect the roles of miR-126a-3p in HUVECs functions in vitro. The in vivo study employed a model of full-thickness excisional wounds in diabetic subjects to explore the potential therapeutic benefits of TEXs. Immunohistochemical and immunofluorescent techniques were utilized to evaluate histological changes in skin tissues. RESULTS: The findings suggested that TEXs facilitate diabetic wound healing through the activation of cell migration, proliferation, and angiogenesis. An upregulation of miR-126a-3p has been observed in TEXs, and it has demonstrated efficient transferability from 4T1 cells to HUVEC cells. The activation of the PI3K/Akt pathway has been attributed to miR-126a-3p derived from TEXs. CONCLUSIONS: The promotion of chronic wound healing can be facilitated by TEXs through the activation of cellular migration, proliferation, and angiogenesis. The activation of the PI3K/Akt pathway by miR-126a-3p originating from TEXs has been discovered, indicating a potential avenue for enhancing the regenerative capabilities of wounds treated with TEXs.

Research on factors influencing Chinese parents' support for death education: a cross-sectional survey.

Objective: This study aims to explore the factors influencing Chinese parents' attitudes toward death education. Given the current lack of such education in China, this research is particularly significant. Death education is vital for shaping the values of young people and alleviating mental health issues, such as depression and suicidal tendencies. By identifying these influencing factors, this study seeks to provide guidance for policymakers and educators in promoting the development and widespread adoption of death education. Methods: To do so, a national cross-sectional quota sample of 12,435 Chinese parents was used. Borrowing from social-ecological theory, the researchers carried out multiple stepwise regression analyses to examine the individual, family, and social-level factors that shape the supportive attitudes of Chinese parents toward death education. Results: The findings revealed that at the individual level, parent (ß = 0.04, p < 0.001), education level (ß = 0.07, p < 0.001), and religious belief (ß = -0.02, p < 0.05) were significant predictors of Chinese parents' support for death education. Meanwhile, at the family and social level, average monthly household income (ß = 0.07, p < 0.001), family health (ß = 0.03, p < 0.05), family communication (ß = 0.02, p < 0.05), social support (ß = 0.15, p < 0.001), neighborhood relations (ß = 0.11, p < 0.001), and social network size (ß = 0.05, p < 0.001) were significant predictors of Chinese parents' supportive attitudes toward death education. Conclusion: Based on these findings, it is suggested that the relevant development, planning, publicity, and public welfare groups and government departments should promote death education, provide more social support, and encourage neighborhood harmony. As higher education and average monthly household income were found to significantly impact the support, the government should improve access to higher education and actively work to increase residents' income to facilitate the development of death education.

A pan-cancer analysis of Dyskeratosis congenita 1 (DKC1) as a prognostic biomarker.

BACKGROUND: Dyskeratosis congenita 1 (DKC1), a critical component of telomerase complex, is highly expressed in a variety of human cancers. However, the association of DKC1 with cancer occurrence and development stages is not clear, making a pan-cancer analysis crucial. METHODS: We conducted a study using various bioinformatic databases such as TIMER, GEPIA, UALCAN, and KM plotter Analysis to examine the different expressions of DKC1 in multiple tissues and its correlation with pathological stages. Through KEGG analysis, GO enrichment analysis and Venn analysis, we were able to reveal DKC1-associated genes and signaling pathways. In addition, we performed several tests including the CCK, wound healing assay, cell cycle arrest assay, transwell assay and Sa-ß-gal staining on DKC1-deleted MDA-231 cells. RESULTS: Our study demonstrates that DKC1 has relatively low expression specificity in different tissues. Furthermore, we found that in ACC, KICH, KIRP and LIHC, the expression level of DKC1 is positively correlated with pathological stages. Conversely, in NHSC, KIRP, LGG, LIHC, MESO and SARC, we observed a negative influence of DKC1 expression level on the overall survival rate. We also found a significant positive correlation between DKC1 expression and Tumor Mutational Burden in 14 tumors. Additionally, we observed a significantly negative impact of DKC1 DNA methylation on gene expression at the promoter region in BRCA. We also identified numerous phosphorylation sites concentrated at the C-terminus of the DKC1 protein. Our GO analysis revealed a correlation between DKC1 and ribosomal biosynthesis pathways, and the common element UTP14A was identified. We also observed decreased rates of cell proliferation, migration and invasion abilities in DKC1-knockout MDA-MB-231 cell lines. Furthermore, DKC1-knockout induced cell cycle arrest and caused cell senescence. CONCLUSIONS: Our findings suggest that the precise expression of DKC1 is closely associated with the occurrence and developmental stages of cancer in multiple tissues. Depletion of DKC1 can inhibit the abilities of cancer cells to proliferate, migrate, and invade by arresting the cell cycle and inducing cell senescence. Therefore, DKC1 may be a valuable prognostic biomarker for the diagnosis and treatment of cancer in various tissues.

Synergistic wound repair effects of a composite hydrogel for delivering tumor-derived vesicles and S-nitrosoglutathione.

Treating chronic wounds requires transition from proinflammatory M1 to anti-inflammatory M2 dominant macrophages. Based on the role of tumor extracellular vesicles (tEVs) in regulating the phenotypic switching from M1 to M2 macrophages, we propose that tEVs may have a beneficial impact on alleviating the overactive inflammatory microenvironment associated with refractory wounds. On the other hand, as a nitric oxide donor, S-nitrosoglutathione (GSNO) can regulate inflammation, promote angiogenesis, enhance matrix deposition, and facilitate wound healing. In this study, a guar gum-based hydrogel with tEVs and GSNO was designed for the treatment of diabetic refractory wounds. This hybrid hydrogel was formed through the phenyl borate bonds, which can automatically disintegrate in response to the high reactive oxygen species (ROS) level at the site of refractory diabetic wounds, releasing tEVs and GSNO. We conducted a comprehensive evaluation of this hydrogel in vitro, which demonstrated excellent performance. Meanwhile, using a full-thickness excision model in diabetic mice, the wounds exposed to the therapeutic hydrogel healed completely within 21 days. The increased closure rate was associated with macrophage polarization and collagen deposition, accelerated fibroblast proliferation, and increased angiogenesis in the regenerating tissues. Therefore, this multifunctional hybrid hydrogel appears to be promising for clinical applications.

Correlation between color doppler flow pattern and molecular biology in elderly patients with colon cancer.

OBJECTIVE: To investigate the correlation between the grade and type of color Doppler flow imaging (CDFI) and tumor-related cytokines in elderly patients with colon cancer. METHODS: Seventy-six elderly patients with colorectal cancer admitted to Zhejiang Provincial People's Hospital from July 2020 to June 2022 were selected. CDFI was used to analyze the blood flow grade and distribution type of tumor tissues, and ELISA was used to detect the levels of tumor-related cytokines in serum. Preoperative clinical data were collected and analyzed, and the correlation between measured cytokine levels and CDFI analysis results was further explored. RESULTS: CDFI blood flow grade showed significant difference in the different lengths, invasion depths and lymph node metastasis of tumors (all P < 0.001). In addition, serum levels of TNF-α, IL-6 and VEGF also showed statistical difference in all above different tumor-related factors (all P < 0.001). Further Pearson correlation analysis showed that CDFI blood flow grade and distribution types were both significantly positively correlated with above serum cytokine levels (r > 0, all P < 0.001). Kaplan-Meier survival analysis showed that both CDFI blood flow grade and distribution types were poor prognostic factors in elderly patients with colon cancer. Regression analysis showed that serum levels of TNF-α, IL-6 and VEGF were independent risk factors for poor prognosis of colon cancer in elderly patients. CONCLUSION: CDFI blood flow grade and tumor tissue distribution have potential significant correlations with tumor-associated cytokines in the serum of colon cancer patients. CDFI blood flow grading technique provides an important imaging method for dynamic observation of angiogenesis and blood flow changes in elderly patients with colon cancer. Abnormal changes in serum levels of tumor-related factors can be used as sensitive indicators to evaluate the therapeutic effect and prognosis of colon cancer.

Effect of La2 O3 and CeO2 on anaerobic methanogenesis process: Kinetics analysis and process mechanism study.

La2 O3 and CeO2 , as main rare earth oxides, with unique physical and chemical properties have been widely used in catalyst and grinding industry. In this study, the effects of La2 O3 and CeO2 on the anaerobic process were investigated. The biological methane production tests showed that 0-0.05 g/L La2 O3 and 0-0.05 g/L CeO2 enhanced anaerobic methanogenesis process. The result showed maximum specific methanogenic rates of La2 O3 and CeO2 were 56.26 mL/(h·gVSS) and 49.43 mL/(h·gVSS) and, compared with the control, increased 4% and 3%, respectively. La2 O3 significantly reduced the accumulation of volatile fatty acids (VFAs), whereas CeO2 had no similar effect. Dissolution experiments demonstrated that the content of extracellular La in the anaerobic granular sludge reached 404 µg-La/g volatile suspended solid (VSS), which was 134 times higher than that of extracellular Ce (3 µg-Ce/gVSS). The content of intracellular La reached 206 µg-La/gVSS, which was 19 times higher than that of intracellular Ce (11 µg-Ce/gVSS). The different stimulation between La3+ and Ce3+ could be attributed to the different dissolution of La2 O3 and CeO2 . The result of this work is helpful to optimize anaerobic processes and to develop novel additives. PRACTITIONER POINTS: Novel anaerobic additives were developed. La2O3 and CeO2 in 0-0.05 g/L enhanced organics degradation and methane production. The addition of La2O3 significantly reduced the accumulation of volatile fatty acids. The solubilization of La2O3 was stronger than CeO2. The promoting effects of low concentrations of La2O3 and CeO2 were derived from dissolved La and Ce.

Water quality assessment based on Nemerow pollution index method: A case study of Heilongtan reservoir in central Sichuan province, China.

In this paper, three monitoring sections were set up in Heilongtan Reservoir, and water samples were collected in 2019, 2020, and 2021 for the determination of physical and chemical properties such as permanganate index, chemical oxygen demand, and biochemical oxygen demand (BOD5). The water quality was evaluated by the single factor pollution index method and the Nemerow pollution index method, and the temporal and spatial changes of water quality were analyzed.The single factor pollution index method determines the water quality category by identifying the single worst indicator of water quality, based on the classified water quality category. The Nemerow pollution index method emphasizes the most polluting factor while also taking into account the contribution of other factors in the assessment system, and determines the water quality category through the comprehensive pollution index. The results of the study indicate that the monitoring indicators of the monitoring sections have reached the Category III water quality standard and above in the "Surface Water Environmental Quality Standard" during the three years 2019 to 2021. The Heilongtan Reservoir's water quality in 2019, 2020, and 2021 is of Category I standard, according to the results of the evaluation of water quality using the single factor pollution index technique. According to the Nemerow pollution index method's results for evaluating water quality, the water quality pollution index for the three monitoring sections as a whole ranges from 0.36 to 0.51 in three years. The three monitoring sections' water quality-Dongfeng Canal, Longmiao, and Sixin Village-has not changed significantly during that time, remaining clean. In terms of temporal and spatial rates of change, the temporal rate of change (T) and spatial rate of change (S) over the three years were less than 20%, and the changes in water quality at each monitoring site were not significant.

Water quality assessment of Lugu Lake based on Nemerow pollution index method.

In this paper, three monitoring sections were set up in Lugu Lake, and water samples were collected in 2019, 2020, and 2021 for the determination of physical and chemical properties such as permanganate index, chemical oxygen demand, biochemical oxygen demand (BOD5) and so on. By using the single factor pollution index method and the Nemerow pollution index method, the water quality of three monitoring sections and the whole Lugu Lake was assessed, and the temporal and spatial changes of water quality were analyzed. The findings demonstrate that Lugu Lake's overall water quality is excellent, and that it has not altered significantly in three years.The results of evaluating the water quality by the single factor pollution index method show that, in the past three years, the water quality of the three monitoring sections and the whole of Lugu Lake is Category I, which belongs to no pollution, and the measured indicators all meet the water quality standard of Category I. It can be seen from the evaluation results of the Nemerow index method that the water quality pollution index of Lugu Lake is between 0.22 and 0.34 in the past three years and the water quality evaluation of Changdao Bay, Lake center, Zhaojia Bay and the whole are Category I standards in 2019, 2020 and 2021. In terms of time changes, the water quality of Lugu Lake has remained stable between 2019 and 2021, and the water quality has been good. From the perspective of spatial changes, in 2019 and 2020, the water quality in Lake center is better than the monitoring sections of Changdao Bay and Zhaojia Bay.

Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy.

Ferroptosis is a new mode of cell death, which can be induced by Fenton reaction-mediated lipid peroxidation. However, the insufficient H2O2 and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent ferroptosis. Herein, a self-supplying lipid peroxide nanoreactor was developed to co-delivery of doxorubicin (DOX), iron and unsaturated lipid for efficient ferroptosis. By leveraging the coordination effect between DOX and Fe3+, trisulfide bond-bridged DOX dimeric prodrug was actively loaded into the core of the unsaturated lipids-rich liposome via iron ion gradient method. First, Fe3+could react with the overexpressed GSH in tumor cells, inducing the GSH depletion and Fe2+generation. Second, the cleavage of trisulfide bond could also consume GSH, and the released DOX induces the generation of H2O2, which would react with the generated Fe2+in step one to induce efficient Fenton reaction-dependent ferroptosis. Third, the formed Fe3+/Fe2+ couple could directly catalyze peroxidation of unsaturated lipids to boost Fenton reaction-independent ferroptosis. This iron-prodrug liposome nanoreactor precisely programs multimodal ferroptosis by integrating GSH depletion, ROS generation and lipid peroxidation, providing new sights for efficient cancer therapy.

Arabidopsis thaliana NOP10 is required for gametophyte formation.

The female gametophyte is crucial for sexual reproduction of higher plants, yet little is known about the molecular mechanisms underlying its development. Here, we report that Arabidopsis thaliana NOP10 (AtNOP10) is required for female gametophyte formation. AtNOP10 was expressed predominantly in the seedling and reproductive tissues, including anthers, pollen grains, and ovules. Mutations in AtNOP10 interrupted mitosis of the functional megaspore during early development and prevented polar nuclear fusion in the embryo sacs. AtNOP10 shares a high level of amino acid sequence similarity with Saccharomyces cerevisiae (yeast) NOP10 (ScNOP10), an important component of the H/ACA small nucleolar ribonucleoprotein particles (H/ACA snoRNPs) implicated in 18S rRNA synthesis and rRNA pseudouridylation. Heterologous expression of ScNOP10 complemented the mutant phenotype of Atnop10. Thus, AtNOP10 influences functional megaspore mitosis and polar nuclear fusion during gametophyte formation in Arabidopsis.