•Review recent studies on reliability, vulnerability, and resilience of transportation network.•Definitions, quantitative indices, and analyses of the three concepts are overviewed.•The ...characteristics of, and the relationship among the three concepts are investigated.•We provide remarks on the foci, measurements, and applications of the three concepts.
We review recent studies on transportation network performance under perturbations. Three representative concepts relating to network performance are covered: reliability, vulnerability, and resilience. With an overview of the definitions and the quantitative indices of these three concepts, we analyse and compare their similarities and differences in the context of transportation. These concepts differ from each other in terms of focus, measurement, and application scenario. Numerical examples are conducted to assess these concepts under different perturbation scenarios. The results indicate their rationale in reflecting network performance under perturbations, yet their outputs differ. Moreover, the relationship among the three concepts is intuitively illustrated by the analysis results.
Nanomaterials with intrinsic enzyme-like activities (nanozymes), have been widely used as artificial enzymes in biomedicine. However, how to control their in vivo performance in a target cell is ...still challenging. Here we report a strategy to coordinate nanozymes to target tumor cells and selectively perform their activity to destruct tumors. We develop a nanozyme using nitrogen-doped porous carbon nanospheres which possess four enzyme-like activities (oxidase, peroxidase, catalase and superoxide dismutase) responsible for reactive oxygen species regulation. We then introduce ferritin to guide nitrogen-doped porous carbon nanospheres into lysosomes and boost reactive oxygen species generation in a tumor-specific manner, resulting in significant tumor regression in human tumor xenograft mice models. Together, our study provides evidence that nitrogen-doped porous carbon nanospheres are powerful nanozymes capable of regulating intracellular reactive oxygen species, and ferritinylation is a promising strategy to render nanozymes to target tumor cells for in vivo tumor catalytic therapy.
Molybdenum (Mo)-based compounds with properly engineered nanostructures usually possess improved reversible lithium storage capabilities, which offer great promise to boost the performance of ...lithium-ion batteries (LIBs). Nevertheless, a lack of efficient and high-yield methods for constructing rational nanostructures has largely restricted the application of these potentially important materials. Herein we demonstrate a metal–organic frameworks (MOFs) mediated strategy to successfully synthesize a series of one-dimensional Mo-based/carbon composites with distinct nanostructures. In this process, starting from well-designed MoO3 nanorods, the crystal control growth is first proposed that a layer of MOFs is achieved to be controllably grown on surfaces of MoO3, forming an obvious core–shell structure, and then the adopted precursor can be in situ transformed into MoO2 or Mo2C which are both well confined in conductive porous carbons through direct carbonization at different temperatures, where the MOFs shell serve as both carbon sources and the reactant to react with MoO3 simultaneously. Benefiting from this design, all optimized products exhibit enhanced electrochemical performances when evaluated as anode materials for LIBs, especially the hollow MoO2/C and core–shell Mo2C/C electrodes, show best reversible capacities up to 810 and 530 mAh g–1 even after 600 cycles at a current density of 1 A g–1, respectively. So this work may broaden the application of MOFs as a kind of coating materials and elucidates the attractive lithium storage performances of molybdenum-based compounds.
MicroRNAs play crucial roles in various types of diseases. However, to date, no information about the role of miR-497 in the development of atherosclerosis has been reported. This study investigated ...the possible role of miR-497 in vascular endothelial cell injury during the early stage of atherosclerosis.
The expression level of miR-497 in human umbilical vein endothelial cells (HUVECs) exposed to ox-LDL was detected using qRT-PCR. To perform gain of function and loss of function analyses, miR-497 mimics were transfected into HUVECs, and miR-497 inhibitors were transfected into HUVECs stimulated with ox-LDL. Flow cytometry was used to analyze cell cycle progression and apoptosis. EdU and CCK-8 assays were employed to detect DNA synthesis and cell proliferation, respectively. After bioinformatics prediction, a dual Luciferase Reporter assay was used to analyze the direct target genes of miR-497. The mRNA and protein levels of the target genes were detected using qRT-PCR and western blot analyses, respectively. Caspase-9/3 activity was analyzed to determine the mechanism of endothelial dysfunction.
We showed that miR-497 was significantly upregulated in HUVECs stimulated with ox-LDL. Ectopic expression of miR-497 suppressed cell proliferation, induced apoptosis and increased the activity of caspase-9/3. After verification, Bcl2 and CCND2 were shown to be direct target genes of miR-497 in HUVECs. MiR-497 significantly suppressed cell proliferation by arresting the cell cycle through the CCND2 protein and induced apoptosis through the Bcl2/Bax-caspase9-caspase3 pathway.
Overall, our study shows that miR-497 might play a role in the development of atherosclerosis by inducing apoptosis and suppressing the proliferation of vascular endothelial cells. Therefore, miR-497 could be a potential therapeutic target for the treatment of atherosclerosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lung cancer (LC) is one of the leading causes of cancer-related deaths worldwide, with a significant morbidity and mortality rate, endangering human life and health. The introduction of ...immunotherapies has significantly altered existing cancer treatment strategies and is expected to improve immune responses, objective response rates, and survival rates. However, a better understanding of the complex immunological networks of LC is required to improve immunotherapy efficacy further. Tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs) are significantly expressed by LC cells, which activate dendritic cells, initiate antigen presentation, and activate lymphocytes to exert antitumor activity. However, as tumor cells combat the immune system, an immunosuppressive microenvironment forms, enabling the enactment of a series of immunological escape mechanisms, including the recruitment of immunosuppressive cells and induction of T cell exhaustion to decrease the antitumor immune response. In addition to the direct effect of LC cells on immune cell function, the secreting various cytokines, chemokines, and exosomes, changes in the intratumoral microbiome and the function of cancer-associated fibroblasts and endothelial cells contribute to LC cell immune escape. Accordingly, combining various immunotherapies with other therapies can elicit synergistic effects based on the complex immune network, improving immunotherapy efficacy through multi-target action on the tumor microenvironment (TME). Hence, this review provides guidance for understanding the complex immune network in the TME and designing novel and effective immunotherapy strategies for LC.
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•Vessel endothelial cells regulate the infiltration and response of immune cells.•Lung microbiome are biomarkers for diagnosis, progression, prognosis of lung cancer.•Metabolites, hormones, neurons regulate immune responses of tumor microenvironment.•Crosstalk between tumor microenvironment affects the efficacy of immunotherapy.•Combined enhancement of immune infiltration and response improve immune efficacy.
Analytical studies on the tidal wave propagation in a coastal leaky aquifer commonly assume that the low-permeability aquitard is homogeneous. The aquitard is, however, vertically heterogeneous in ...nature due to varying soil types along the burial depth as can be frequently seen from borehole logs. In this study, an innovative analytical model is developed to explore the vertical heterogeneity in aquitard hydraulic conductivity (K) and specific storage (Ss) on the tidal wave propagation coupling with vertical leakage from the aquitard. The novelty behind the newly derived analytical solution is attributed to the fact that the aquitard along the burial depth can be divided into any number of homogeneous zones, each of which is associated with distinct K and Ss values, so that arbitrary vertical heterogeneity pattern of aquitard K and Ss can be captured. Theoretical analysis results reveal that an interlayer within the aquitard with a smaller K can significantly enhance the amplitude and phase shift of periodic groundwater head fluctuations in the leaky aquifer, while a larger Ss of the interlayer will weaken the amplitude and phase shift provided a relatively small aquitard K. Buried locations of the interlayer also implement non-negligible effects on the tidal wave propagation. For the scenario of exponentially decaying aquitard K and Ss, which is commonly encountered for a thick aquitard, a larger decay exponent results in smaller amplitude and phase shift. This analytical study highlights the importance of vertical aquitard heterogeneity on tidal wave propagation in a coastal leaky aquifer system.
•Develop network-based measures for systematically characterizing the network redundancy.•Develop computational methods for evaluating the network-based redundancy measures.•Extend the route ...diversity measure to consider effective routes.•Employ optimization-based approach to determine network spare capacity.•Demonstrate the complementary feature of the two network redundancy measures.
Redundancy is vital for transportation networks to provide utility to users during disastrous events. In this paper, we develop two network-based measures for systematically characterizing the redundancy of transportation networks: travel alternative diversity and network spare capacity. Specifically, the travel alternative diversity dimension is to evaluate the existence of multiple modes and effective routes available for travelers or the number of effective connections between a specific origin-destination pair. The network spare capacity dimension is to quantify the network-wide residual capacity with an explicit consideration of travelers’ mode and route choice behaviors as well as congestion effect. They can address two fundamental questions in the pre-disaster transportation system evaluation and planning, i.e., "how many effective redundant alternatives are there for travelers in the normal or disruptive event?" and "how much redundant capacity does the network have?" To implement the two measures in practice, computational methods are provided to evaluate the network redundancy. Numerical examples are also presented to demonstrate the features of the two redundancy measures as well as the applicability of the computational methods. The analysis results reveal that the two measures have different characterizations on network redundancy from different perspectives, and they can complement each other by providing meaningful information to both travelers and planners.
Composites of LDPE filled with different amounts of graphene nanoplatelets (GnP) were prepared in form of films by means of precoating technique and single screw melt-extrusion using two types of ...screws, compression and mixing. This manufacturing process imposes strong anisotropy on the sample's morphology, in which the nanoplatelets become oriented along the extrusion direction. Such orientation of GnP in LDPE matrix is confirmed by scanning electron microscopy observations and it yields unique electrical properties. As compared to pure LDPE, significant reductions of the through-plane conductivity are found for the composites at relatively low electric fields (<20 kV/mm) at low filler concentrations. Above the field level of 20 kV/mm, a crossover effect is observed that results in a strong field dependency of the conductivity where the non-linear behavior starts to dominate. Moreover, differential scanning calorimetry (DSC) results indicate a decrease in polymer crystallinity of the composite matrix with increasing filler content, whereas thermogravimetric (TG) analysis shows a slight increase in the material's thermal stability. Application of GnP also leads to improvement of mechanical properties, manifested by the increase of Young's modulus and tensile strength in both types of samples.
► The scaling effect and overlapping problem are examined using the logit-based SUE models. ► The overlapping problem is handled by the recently developed extended logit models. ► The O–D specific ...scaling factor is used to partially relax the identical trip length variance problem. ► Numerical experiments are performed on eight logit-based SUE models. ► The effects of route sets, congestion levels, dispersion intensities, and network asymmetries are also examined.
The purpose of this paper is to examine the scaling effect and overlapping problem in a route choice context using the logit-based stochastic user equilibrium (SUE) principle to explicitly account for the congestion effect. Numerical experiments are performed on nine models: the deterministic user equilibrium model, the multinomial logit SUE model with and without scaling, the C-logit SUE model with and without scaling, the path-size logit SUE model with and without scaling, and the paired combinatorial logit SUE model with and without scaling. Sensitivity analysis is conducted to examine the effects of route sets, congestion levels, dispersion intensities, and network asymmetries. A real transportation network in the City of Winnipeg, Canada is also used to compare the network equilibrium flow allocations of different SUE models. The results of the sensitivity analysis and the Winnipeg network reveal that both scaling effect and overlapping problem can have a significant impact on the network equilibrium flow allocations.
Tumour cells adapt to nutrient deprivation in vivo, yet strategies targeting the nutrient poor microenvironment remain unexplored. In melanoma, tumour cells often experience low glutamine levels, ...which promote cell dedifferentiation. Here, we show that dietary glutamine supplementation significantly inhibits melanoma tumour growth, prolongs survival in a transgenic melanoma mouse model, and increases sensitivity to a BRAF inhibitor. Metabolomic analysis reveals that dietary uptake of glutamine effectively increases the concentration of glutamine in tumours and its downstream metabolite, αKG, without increasing biosynthetic intermediates necessary for cell proliferation. Mechanistically, we find that glutamine supplementation uniformly alters the transcriptome in tumours. Our data further demonstrate that increase in intra-tumoural αKG concentration drives hypomethylation of H3K4me3, thereby suppressing epigenetically-activated oncogenic pathways in melanoma. Therefore, our findings provide evidence that glutamine supplementation can serve as a potential dietary intervention to block melanoma tumour growth and sensitize tumours to targeted therapy via epigenetic reprogramming.