With the steady increase in passenger volume of high-speed railways in China, some high-speed railway sections have faced a difficult situation. To provide more transport services, it is necessary to ...add as many trains as possible in a section to increase capacity. To solve this problem, a compressed multilayer space-time network model is constructed with the maximum number of trains that can be scheduled in the train timetable as the objective. The combination of the train stop plan and speed level is represented by the layer of network where the train is located, and constraints such as train selection, train safety, train overtake and cross-line trains are considered. A method based on timing-cycle iterative optimization is designed to decompose the original problem into multiple subproblems, and the solving order of the subproblems is determined by a heuristic greedy rule. Taking the Beijing-Jinan section of the Beijing-Shanghai high-speed railway as an example, the maximum number of trains was increased by 12.5% compared with the timetable before optimization. The saturated timetables provide detailed schedules, which helps decision-makers better adjust the timetable to run more trains.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Postdoctoral researchers are critical to scholarly advancements, and promoting postdoctoral career growth is an endogenous path to help postdocs break through the "encircled city of scientific ...research". However, further research is needed to fully explore the mechanisms that connect workplace support to postdoctoral career growth.
Drawing from the Conservation of Resources theory, this study proposes a chain mediation model that demonstrates how workplace support enhances career growth by connecting psychological capital with work-life balance. To understand the motivation and career growth of postdocs in China, we conducted two questionnaires in 2021 and 2023 with the support of relevant stations.
Analyzing 367 questionnaires from Chinese postdocs, our research indicates that workplace support has a positive impact on career growth. Additionally, both psychological capital and work-life balance are key factors that contribute to career growth, serving as separate mediators and as part of a chain of mediators.
This study validates the appropriateness of the Conservation of Resources theory in the study of the influence mechanism of postdoctoral career growth and proposes targeted strategies for academic institutions to improve support systems, promoting more effective career development pathways.
Ivabradine not only reduces heart rate but has other cardiac and vascular protective effects including anti-inflammation and anti-oxidation. Since endothelial nitric oxide synthase (eNOS) is a ...crucial enzyme in maintaining endothelial activity, we aimed to investigate the impact of ivabradine in low shear stress (LSS) induced inflammation and endothelial injury and the role of eNOS played in it. Endothelial cells (ECs) were subjected to LSS at 2dyne/cm2, with 1 hour of ivabradine (0.04μM) or LY294002 (10μM) pre-treatment. The mRNA expression of IL-6, VCAM-1 along with eNOS were measured by QPCR. Reactive oxygen species (ROS) was detected by dihydroethidium (DHE) and DCF, and protein phosphorylation was detected by western blot. It demonstrated that ivabradine decreased LSS induced inflammation and oxidative stress in endothelial cells. Western blot showed reduced rictor and Akt-Ser473 as well as increased eNOS-Thr495 phosphorylation. However, mTORC1 pathway was only increased when LSS applied within 30 minutes. These effects were reversed by ivabradine. It would appear that ivabradine diminish ROS generation by provoking mTORC2/Akt phosphorylation and repressing mTORC1 induced eNOS-Thr495 activation. These results together suggest that LSS induced endothelial inflammation and oxidative stress are suppressed by ivabradine via mTORC2/Akt activation and mTORC1/eNOS reduction.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It is well-known that cisplatin exhibited a broad spectrum of anticancer activities against many solid tumors, but its severe toxicity and drug resistance have largely limited wider clinical ...applications. Various strategies have been tried to discover new Pt (II) drugs with at least equal activity as well as low toxicity compared to cisplatin, but the inherent problem remains unsolved. Here we report that Pt (IV) complexes comprising a CA-4 analogue, as dual-targeting Pt (IV) prodrug, were synthesized and evaluated for anti-proliferative activity using MTT assay. Among them, complex 19 displayed most potent activity against the tested cancer cell lines, and simultaneously exhibited better cell selectivity between cancer cells and normal cells than that of cisplatin. Mechanism studies revealed that complex 19 effectively induced cell cycle arrest at the G2/M phase and dramatically disrupted the microtubule organization. Moreover, complex 19 significantly induced cell apoptosis and decreased MMP. Importantly, complex 19 significantly inhibited tumor growth in SK-OV-3 xenograft model in vivo without apparent toxicity.
Display omitted
•Novel Pt (IV) complexes containing CA-4 analogues can inhibit tubulin.•The resulting Pt (IV) complexes exhibited certain ability to overcome cisplatin resistance.•Complex 19 displayed higher cytotoxicity and lower toxicity than cisplatin.•19 effectively inhibited tumor growth in SK-OV-3 xenograft model in vivo.•19 might induce cell apoptosis through mitochondrion pathway.
The high quality waste heat recovery of the molten blast furnace slag was necessary and urgent. In this paper, the flow characteristic of the molten slag reactor was investigated by numerical ...simulation. Firstly, the three-dimensional model was established for investigating the gas-liquid two-phase flow. The gas-liquid flow was modeled to be turbulent, which was described by the RNG k-ε model, and the interface of gas and liquid was conducted by the VOF model. Secondly, the top-submerged cold experiment system was constructed to validate the accuracy of the simulation model. Thirdly, the bubble behavior, gas phase distribution and molten slag motion were investigated. The bubble in the reactor would go through five stages and the maximum gas fraction reached about 4.87% at 0.75s. Meanwhile, the gas phase distribution and molten slag motion were closely related to the bubble behavior. Ultimately, the matrix analysis method was applied to obtain the optimal parameters of the reactor. The optimal condition improved the flow behavior in the molten BFS reactor significantly. The present results of the simulation provided an insight for the gas-liquid two-phase flow in molten slag reactor, which would provide the theoretical guidance for industrial applications.
•Gas-liquid interaction characteristic in molten slag was investigated in detail.•Bubble behavior was grasped by simulation and validated by cold experiment.•The changing of gas phase distribution and liquid motion with bubble were obtained.•Optimal structure and operation parameters were obtained by matrix analysis method.
Six novel platinum(II) complexes 1–6 bearing different furoxan moieties as nitric oxide (NO) donors have been designed, synthesized, and characterized by elemental analysis and 1H NMR, IR, and ESI-MS ...spectroscopy. The furoxan groups were introduced to the platinum complexes to release NO, which may take synergic action with the platinum-based moieties on the tumor cells. It was found that all compounds exhibited considerable cytotoxicity against human HCT-116 and SGC-7901 cell lines via DNA binding together with NO-releasing features, especially for compound 3. This finding is in accordance with the previous reports that NO hybrids show higher cytotoxicity against colon cancer cell lines compared with their parent compounds.
Flavonoids are one of the most important bioactive components in litchi (
Sonn.) seeds and have broad-spectrum antiviral and antitumor activities. Litchi seeds have been shown to inhibit the ...proliferation of cancer cells and induce apoptosis, particularly effective against breast and liver cancers. Elucidating the distribution of flavonoids is important for understanding their physiological and biochemical functions and facilitating their efficient extraction and utilization. However, the spatial distribution patterns and expression states of flavonoids in litchi seeds remain unclear. Herein, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used for
detection and imaging of the distribution of flavonoids in litchi seed tissue sections for the first time. Fifteen flavonoid ion signals, including liquiritigenin, apigenin, naringenin, luteolin, dihydrokaempferol, daidzein, quercetin, taxifolin, kaempferol, isorhamnetin, myricetin, catechin, quercetin 3-β-d-glucoside, baicalin, and rutin, were successfully detected and imaged
through MALDI-MSI in the positive ion mode using 2-mercaptobenzothiazole as a matrix. The results clearly showed the heterogeneous distribution of flavonoids, indicating the potential of litchi seeds for flavonoid compound extraction. MALDI-MS-based multi-imaging enhanced the visualization of spatial distribution and expression states of flavonoids. Thus, apart from improving our understanding of the spatial distribution of flavonoids in litchi seeds, our findings also facilitate the development of MALDI-MSI-based metabolomics as a novel effective molecular imaging tool for evaluating the spatial distribution of endogenous compounds.
Spent fluid catalytic cracking catalysts (S-FCC-Cs) constitutes a fraction of the hazardous solid waste generated in the petrochemical industry. The resource application of S-FCC-Cs remains a ...challenge. This study aims to explore utilizing S-FCC-Cs in asphalt mortar as a means to enhance resource utilization. Five different S-FCC catalysts were used as substitutes for mineral powder in the asphalt slurry at varying proportions. The high-temperature rheology of the resulting spent FCC catalyst-modified asphalt slurry was analyzed using temperature scanning tests and multiple stress creep recovery (MSCR) tests conducted at different temperatures and substitution doping levels. As the proportion of alternative doping increased, both the phase angle and irrecoverable creep flexibility decreased, while the absolute values of the rutting factor, deformation recovery rate, and irrecoverable creep flexibility difference increased. Moreover, as the temperature rose, the phase angle increased while the rutting factor decreased. The inclusion of an alternative admixture significantly improved the high-temperature performance of the asphalt mastic. This improvement was attributed to several factors, including the increase in the elastic component, enhanced deformation resistance, and improved deformation recovery. While the high-temperature performance of spent FCC catalyst-modified asphalt mastic gradually declined with increasing test temperature, all performance indices remained superior to those of limestone mineral powder asphalt mastic. In addition, the asphalt mortar modified by S-FCC-C JX with a surface area and hydrophilic coefficient of 105 m2/g and 1.026, respectively, exhibited the best rutting resistance and resilience performances among the five mortars, suggesting that the two factors co-affected the high-temperature rheological properties of S-FCC-C asphalt mortar. Considering stress sensitivity, it is more advantageous in improving the high-temperature deformation resistance of asphalt slurry at the JX dosage of 20%. These research findings offer valuable guidance for the application of S-FCC catalysts in asphalt pavement.
Background. Oscillatory shear stress (OSS) disrupts endothelial homeostasis and promotes oxidative stress, which can lead to atherosclerosis. In atherosclerotic lesions, Toll-like receptor 4 (TLR4) ...is highly expressed. However, the molecular mechanism by which TLR4 modulates oxidative changes and the cell signaling transudation upon OSS is yet to be determined. Methods and Results. Carotid artery constriction (CAC) surgery and a parallel-plate flow chamber were used to modulate shear stress. The results showed that OSS significantly increased the oxidative burden, and this was partly due to TLR4 activation. OSS activated NOX2 and had no significant influence to NOX1 or NOX4 in endothelial cells (ECs). OSS phosphorylated caveolin-1, promoted its binding with endothelial nitric oxide synthase (eNOS), and resulted in deactivation of eNOS. TLR4 inhibition restored levels of nitric oxide (NO) and superoxide dismutase (SOD) in OSS-exposed cells. Conclusion. TLR4 modulates OSS-induced oxidative stress by activating NOX2 and suppressing eNOS.
Glioma and pancreatic cancer are tumors with a high degree of malignancy, morbidity, and mortality. The present study explored possible molecular mechanisms and potential diagnostic and prognostic ...biomarker-PLPP4 of glioma and PAAD. PLPP4 is differentially elevated in glioma and PAAD tissues. Statistical analysis from TCGA demonstrated that high expression of PLPP4 significantly and positively correlated with clinicopathological features, including pathological grade and poor overall survival in glioma and PAAD patients. Following this, the methylation levels of PLPP4 also affected overall survival in clinical tissue samples. Silencing PLPP4 inhibited proliferation, invasion, and migration in LN229 cells and PANC-1 cells. Moreover, the combination of multiple proteins for the prognosis prediction of glioma and PAAD was evaluated. These results were conducted to elaborate on the potential roles of the biomarker-PLPP4 in clonability and invasion of glioma and PAAD cells.