Treatments of glioblastoma (GBM) have not been very effective, largely due to the inefficiency of drugs in penetrating the blood brain barrier (BBB). In this study, we investigated the potential of exosome-coated doxorubicin (DOX)-loaded nanoparticles (ENP DOX) in BBB penetration, inducing immunogenic cell death (ICD) and promoting survival of GBM-bearing mice. DOX-loaded nanoparticles (NP DOX) were coated with exosomes prepared from mouse brain endothelial bEnd.3 cells. ENP DOX cellular uptake was examined. Penetration of ENP DOX through the BBB was tested in an in vitro transwell system and a GBM mouse model. The effects of ENP DOX in inducing apoptosis and ICD were assessed. Finally, the efficacy of ENP DOX in the treatment of GBM-bearing mice was assessed. ENP DOX was taken up by bEnd.3 cells and could penetrate the BBB both in vitro and in vivo. In vitro, END DOX induced apoptosis and ICD of glioma GL261 cells. Systemic administration of ENP DOX resulted in maturation of dendritic cells, activation of cytotoxic cells, altered production of cytokines, suppressed proliferation and increased apoptosis of GBM cells in vivo and prolonged survival of GBM-bearing mice. Our findings indicate that ENP DOX may be a potent therapeutic strategy for GBM which warrants further investigation in clinical application. K E Y W O R D S blood brain barrier, doxorubicin, exosome-coated doxorubicin-loaded nanoparticle, glioblastoma, immunogenic cell death 1 | INTRODUCTION Glioblastoma (GBM) is a highly aggressive brain tumor with an extremely poor prognosis and a small rate (4%-5%) or 5-year survival. 1 Current treatments of GBM include surgeries, radiotherapy, and/or chemotherapy. These treatments not only cause severe side effects, but also only slightly improve the overall median survival (only 15 months) and 5-year survival rate. 2 Although many therapeutic strategies targeting have been developed, their application in the clinic for treatment GBM has been largely impeded due to the lack of safe and efficient drug delivery system that delivers drugs to tumor location. 3 Recent research findings suggest that, in various cancer types including GBM, human immune response has significant potential in promoting immune mediated tumor eradication and improving long term survival. 4 Recent studies have shown that anthracyclines, such as doxorubicin (DOX), not only induce apoptosis of tumor cells, but also

Nitrogen (N) is an essential major nutrient for food crops. Although ammonium (NH 4 + ) is the primary N source of rice (Oryza sativa), nitrate (NO 3 À ) can also be absorbed and utilized. Rice responds to NO 3 À application by altering its root morphology, such as root elongation. Strigolactones (SLs) are important modulators of root length. However, the roles of SLs and their downstream genes in NO 3 À -induced root elongation remain unclear. Here, the levels of total N and SL (4-deoxyorobanchol) and the responses of seminal root (SR) lengths to NH 4 + and NO 3 À were investigated in rice plants. NO 3 À promoted SR elongation, possibly due to short-term signal perception and long-term nutrient function. Compared with NH 4 + conditions, higher SL signalling/levels and less D53 protein were recorded in roots of NO 3 À -treated rice plants. In contrast to wildtype plants, SR lengths of d mutants were less responsive to NO 3 À conditions, and application of rac-GR24 (SL analogue) restored SR length in d10 (SL biosynthesis mutant) but not in d3, d14, and d53 (SL-responsive mutants), suggesting that higher SL signalling/levels participate in NO 3 À-induced root elongation. D53 interacted with SPL17 and inhibited SPL17-mediated transactivation from the PIN1b promoter. Mutation of SPL14/17 and PIN1b caused insensitivity of the root elongation response to NO 3 À and rac-GR24 applications. Therefore, we conclude that perception of SLs by D14 leads to degradation of D53 via the proteasome system, which releases the suppression of SPL14/17-modulated transcription of PIN1b, resulting in root elongation under NO 3 À supply.

A B S T R A C TCeO 2 and TiO 2 engineered nanoparticles (ENPs) are being increasingly used in many applications. Due to their properties, heteroaggregation between these two types of ENPs is very likely, which can determine their fate and transport. However, the heteroaggregation behavior of CeO 2 and TiO 2 ENPs is still not clear, partly due to the lack of appropriate tools. In this study, we investigated the application of Turbiscan Stability Index (TSI) for the measurements of CeO 2 /TiO 2 ENP heteroaggregation. TSI was found to be effective to investigate the heteroaggregation and stability of the CeO 2 -TiO 2 ENPs system. Increasing CeO 2 /TiO 2 ENPs ratio reduces the TSI values, indicating higher stability. Fluorescence excitation-emission matrix (EEM) spectra were used to study the interface interaction between humic acid (HA) and CeO 2 /TiO 2 ENPs. The TSI value of ENPs were rising with the increasing of CeO 2 /TiO 2 ENPs ratios in the H River or Q Reservoir water. In addition, their variation trends were http://dx

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Background and Objective: Exosomes communicate inter-cellularly and miRNAs play critical roles in this scenario. MiR-214-5p was implicated in multiple tumors with diverse functions uncovered. However, whether miR-214-5p is mechanistically involved in glioblastoma, especially via exosomal pathway, is still elusive. Here we sought to comprehensively address the critical role of exosomal miR-214-5p in glioblastoma (GBM) microenvironment. Methods: The relative expression of miR-214-5p was determined by real-time PCR. Cell viability and migration were measured by MTT and transwell chamber assays, respectively. The secretory cytokines were measured with ELISA kits. The regulatory effect of miR-214-5p on CXCR5 expression was interrogated by luciferase reporter assay. Protein level was analyzed by Western blot. Results: We demonstrated that miR-214-5p was aberrantly overexpressed in GBM and associated with poorer clinical prognosis. High level of miR-214-5p significantly contributed to cell proliferation and migration. GBM-derived exosomal miR-214-5p promoted inflammatory response in primary microglia upon lipopolysaccharide challenge. We further identified CXCR5 as the direct target of miR-214- 5p in this setting. Conclusion: Overexpression of miR-214-5p in GBM modulated the inflammatory response in microglia via exosomal transfer.

Objective. To investigate the value of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and red blood cell distribution width (RDW) in evaluating the prognosis of children with severe pneumonia (SP). Methods. A retrospective analysis of the data of 91 children with SP admitted to our hospital from March 2018 to March 2021. According to the survival status after 28 days of treatment, all children were divided into the survival group (n = 59) and the death group (n = 32). The clinical data and laboratory indicators of the patients were recorded. Multivariate logistic regression was used to analyze the risk factors of prognosis, and the ROC curve was used to analyze the predictive value of each index. Results. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score and CURB-65 score of the death group were higher than those of the survival group ( P < 0.05 ). The RDW, NLR, PLR, and high-sensitivity C-reactive protein, procalcitonin blood lactic acid (Lac) of the death group, were higher than those of the survival group, and LYM was lower than the survival group ( P < 0.05 ). Multivariate regression analysis showed that APACHE II score, RDW, NLR, PLR, and Lac were all independent risk factors for poor prognosis in children with SP ( P < 0.05 ). The AUC of NLR, PLR, and RDW for evaluating the prognosis of children with SP were 0.798, 0.781, and 0.777, respectively. The sensitivity was 56.25%, 90.63%, and 56.25%, respectively, and the specificity was 89.83%, 55.93%, and 91.53%, respectively. The AUC of NLR, PLR, and RDW combined to evaluate the prognosis of children with SP was 0.943. When the best cut-off value was 0.8528, the sensitivity was 93.75%, and the specificity was 91.53%. Conclusion. NLR, PLR, and RDW have certain predictive value for the prognosis of children with SP; the combination of the three indicators has a higher value in evaluating the prognosis of children with SP, which can better guide the prognostic treatment.

Liberia is endowed with an impressive stock of mineral reserves and has traditionally relied on mining, namely iron ore, gold, and diamonds, as a major source of income. The recent growth in the mining sector has the potential to contribute significantly to employment, income generation, and infrastructure development. However, the development of these mineral resources has significant environmental impacts that often go unnoticed. This paper presents an overview of the Liberian mining sector from historical, current development, and economic perspectives. The efforts made by government to address issues of environmental management and sustainable development expressed in national and international frameworks, as well as some of the environmental challenges in the mining sector are analyzed. A case study was conducted on one of the iron ore mines (China Union Bong Mines Investment) to analyze the effects of the water quality on the local water environment. The results show that the analyzed water sample concentrations were all above the WHO and Liberia water standard Class I guidelines for drinking water. Finally the paper examines the application of water footprint from a life cycle perspective in the Liberian mining sector and suggests some policy options for water resources management.

At present, the dealkalization and comprehensive utilization of red mud is a worldwide problem. Studies on the settling performance and phase transformation of red mud by HCl, CaO, and HO leaching are limited. In this study, the characteristics of red mud were systematically analyzed. The average sizes of graded and initial red mud were 4.11 and 9.20 μm, respectively. X-ray diffraction (XRD), X-ray fluorescence spectra (XRF), and thermogravimetry-differential scanning calorimetry (TG-DSC) results indicated the different mineralogical phases, composition, and thermal behavior. The addition of HCl could neutralize the alkalization in the red mud slurry, and CaO could replace the Na and K. Notably, the pH of the red mud slurry had no obvious change with the increase in water washing times in a certain pH. Interestingly, soluble Al and Fe were not detected in the HCl-red mud and CaO-red mud. In addition, the settling ratio was used to express the settling performance of the red mud slurry. Their interaction mechanisms were proposed, which may include phase transformation and the changing of the size and surface area. The research provided a better understanding of the phase transformation and settling performance in the treatment of red mud by HCl, CaO, and HO leaching.