Ferroptosis is gaining followers as mechanism of selective killing cancer cells in a non-apoptotic manner, and novel nanosystems capable of inducing this iron-dependent death are being increasingly developed. Among them, polydopamine nanoparticles (PDA NPs) are arousing interest, since they have great capability of chelating iron. In this work, PDA NPs were loaded with Fe3+ at different pH values to assess the importance that the pH may have in determining their therapeutic activity and selectivity. In addition, doxorubicin was also loaded to the nanoparticles to achieve a synergist effect. The in vitro assays that were performed with the BT474 and HS5 cell lines showed that, when Fe3+ was adsorbed in PDA NPs at pH values close to which Fe(OH)3 begins to be formed, these nanoparticles had greater antitumor activity and selectivity despite having chelated a smaller amount of Fe3+. Otherwise, it was demonstrated that Fe3+ could be released in the late endo/lysosomes thanks to their acidic pH and their Ca2+ content, and that when Fe3+ was co-transported with doxorubicin, the therapeutic activity of PDA NPs was enhanced. Thus, reported PDA NPs loaded with both Fe3+ and doxorubicin may constitute a good approach to target breast tumors. 相似文献
Longitudinal analyses on normal versus impaired functioning across 7 domains were conducted in children who had experienced profound institutional deprivation up to the age of 42 months and were adopted from Romania into U.K. families. Comparisons were made with noninstitutionalized children adopted from Romania and with nondeprived within-U.K. adoptees placed before the age of 6 months. Specifically, the validity of the assessment, the degree of continuity and change in levels of functioning from 6 to 11 years, and the factors in the pre- and postadoption environment accounting for heterogeneity in outcome were examined. Pervasive impairment was significantly raised in children experiencing institutional deprivation for ≥6 months of life, with a minority within this group showing no impairment. There was no additional significant effect of duration of deprivation beyond the 6-month cutoff, and few other predictors explained outcome. The pattern of normality/impairment was mainly established by 6 years of age, with considerable continuity at the individual level between 6 and 11 years. The findings are discussed in terms of the possibility of a sensitive period for development. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
A survey of aflatoxin B1 (AFLB1) levels in commonly used commercial shrimp finisher feeds in the Philippines showed a various range of values from not detected to 120 μg kg?1 using high-performance thin-layer chromatography. Six experimental diets were prepared to contain various levels of AFLB1 based on survey results to determine the effects of such contamination in pre-adult shrimp Penaeus monodon (17.5 ± 0.6 g). Results showed that shrimps fed diets containing AFLB1 greater than or equal to 73.8 μg kg?1 gave comparatively poor growth rate and higher susceptibility to shell diseases. No AFLB1 residues were detected in sampled whole shrimp tissues after 62 days of exposure to AFLB1 containing diets indicating a low potential for transmission of the toxin from edible shrimp tissues to consumers. Histopathological alterations in the hepatopancreas of shrimp chronically exposed to AFLB, were observed in all samples. The degree of alterations correlated with the level of AFLB1. Based on growth performance, pre-adult shrimps can tolerate AFLB1 levels of up to 52.3 μg kg?1 in the feeds although histopathological changes were already evident in the tissues of shrimps given diets with 26.5 μg kg?1 AFLB1. 相似文献
Ca2+ signaling has been involved in controling critical cellular functions such as activation of proteases, cell death, and cell cycle control. The endoplasmatic reticulum plays a significant role in Ca2+ storage inside the cell, but mitochondria have long been recognized as a fundamental Ca2+ pool. Protozoan parasites such as Plasmodium falciparum, Toxoplasma gondii, and Trypanosoma cruzi display a Ca2+ signaling toolkit with similarities to higher eukaryotes, including the participation of mitochondria in Ca2+-dependent signaling events. This review summarizes the most recent knowledge in mitochondrial Ca2+ signaling in protozoan parasites, focusing on the mechanism involved in mitochondrial Ca2+ uptake by pathogenic protists. 相似文献
The oxygen reduction reaction (ORR) is essential in research pertaining to life science and energy. In applications, platinum-based catalysts give ideal reactivity, but, in practice, are often subject to high costs and poor stability. Some cost-efficient transition metal oxides have exhibited excellent ORR reactivity, but the stability and durability of such alternative catalyst materials pose serious challenges. Here, we present a facile method to fabricate uniform CoxOy nanoparticles and embed them into N-doped carbon, which results in a composite of extraordinary stability and durability, while maintaining its high reactivity. The half-wave potential shows a negative shift of only 21 mV after 10,000 cycles, only one third of that observed for Pt/C (63 mV). Furthermore, after 100,000 s testing at a constant potential, the current decreases by only 17%, significantly less than for Pt/C (35%). The exceptional stability and durability results from the system architecture, which comprises a thin carbon shell that prevents agglomeration of the CoxOy nanoparticles and their detaching from the substrate.
A combinatorial characterization is given for those one-rule Thue systems of the form {(w1,w2)} with 0 |w2||ov(w1)| that are Church-Rosser. Here ov(w1) denotes the longest proper self-overlap ofw1. Further, it is shown that a Thue system of this form is Church-Rosser if and only if there is an equivalent Thue system that is Church-Rosser.This research was supported in part by the National Science Foundation under Grant No. MCS83-14977. It was performed while the first author was visiting the Department of Mathematics of the University of California at Santa Barbara. 相似文献
Summary The complements of an AFL form an AFL if and only if is closed under length-preserving universal quantification. The complements of the context-sensitive languages form a principal AFL with a hardest set L1. The context-sensitive languages are closed under complementation if and only if L1 is context-sensitive.This research was supported in part by the National Science Foundation under Grants MCS76-10076 and DCR74-15091 相似文献
Important advances in natural calligraphic interfaces for CAD (Computer Aided Design) applications are being achieved, enabling the development of CAS (Computer Aided Sketching) devices that allow facing up to the conceptual design phase of a product. Recognizers play an important role in this field, allowing the interpretation of the user’s intention, but they still present some important lacks. This paper proposes a new recognition paradigm using an agent-based architecture that does not depend on the drawing sequence and takes context information into account to help decisions. Another improvement is the absence of operation modes, that is, no button is needed to distinguish geometry from symbols or gestures, and also “interspersing” and “overtracing” are accomplished. 相似文献
Nanoparticles of metal–organic frameworks (MOF NPs) are crystalline hybrid micro- or mesoporous nanomaterials that show great promise in biomedicine due to their significant drug loading ability and controlled release. Herein, we develop porous capsules from aggregate of nanoparticles of the iron carboxylate MIL-100(Fe) through a low-temperature spray-drying route. This enables the concomitant one-pot encapsulation of high loading of an antitumor drug, methotrexate, within the pores of the MOF NPs, and the collagenase enzyme (COL), inside the inter-particular mesoporous cavities, upon the formation of the capsule, enhancing tumor treatment. This association provides better control of the release of the active moieties, MTX and collagenase, in simulated body fluid conditions in comparison with the bare MOF NPs. In addition, the loaded MIL-100 capsules present, against the A-375 cancer cell line, selective toxicity nine times higher than for the normal HaCaT cells, suggesting that MTX@COL@MIL-100 capsules may have potential application in the selective treatment of cancer cells. We highlight that an appropriate level of collagenase activity remained after encapsulation using the spray dryer equipment. Therefore, this work describes a novel application of MOF-based capsules as a dual drug delivery system for cancer treatment. 相似文献