Abstract Background The triglyceride-glucose (TyG) index is a risk marker for arterial stiffness; however, the extent to which the TyG index is associated with arterial stiffness via lipids and ...inflammation remains unknown. The first aim was to probe the relationship between the TyG index and arterial stiffness in two surveys. The second aim was to clarify whether lipids and inflammation mediate this relationship. Methods The sample size of 13,726 U.S. individuals from the National Examination Survey (NHANES) and 3,964 Chinese individuals from the China Health and Retirement Longitudinal Study (CHARLS 2015) were enrolled. Weighted multivariate logistic and linear regression models, as well as restricted cubic spline (RCS) and mediation analyses, were utilized to estimate complex relationships between the TyG index, arterial stiffness, lipids (non-high-density lipoprotein cholesterol non-HDL-C) and inflammation (C-reactive protein CRP) biomarkers. Results A total of 3,420 U.S. patients and 992 Chinese patients were diagnosed with increased arterial stiffness. Regression analyses demonstrated that higher quartiles of the TyG index were associated with a greater incidence of increased arterial stiffness (NHANES: OR = 2.610, 95% CI = 2.043–3.334, P < 0.001; CHARLS: OR = 1.579, 95% CI = 1.057–2.360, P < 0.001). Participants with a higher TyG index/higher CRP level or with a higher TyG index/higher non-HDL-C level had the highest incidence of increased arterial stiffness in the two surveys. The results were still consistent when the sensitivity analysis was implemented with stricter clinical cut-off values of non-HDL-C. Mediation analysis verified that lipids (mediated effect: β = 0.012, P < 0.001 in NHANES; β = 0.020, P < 0.001 in CHARLS) and inflammation (mediated effect: β = 0.003, P < 0.001 in NHANES; β = 0.006, P < 0.001 in CHARLS) partially mediated this relationship. Conclusions These results indicated a positive linear correlation between the TyG index, non-HDL-C level, CRP level and increased arterial stiffness in two surveys. Furthermore, lipids and inflammation could partly mediate the correlation of the TyG index with arterial stiffness in both surveys.
A modified precipitation method was used to prepare yttria powers for the fabrication of yttria ceramics in this study. The precipitation behavior, phase evolution, and shape of the yttria precursor ...were all examined in the presence or absence of an electric field. The findings demonstrate that the phases of the yttria precursor were Y
(CO
)
·2H
O with and without an electric field, while the morphology changed from flake to needle-like under the action of the electric field. After calcining both yttria precursors at 750 °C, yttria powders with similar morphologies were obtained and then densified via conventional sintering (CS) and spark plasma sintering (SPS). The densification and thermal shock resistance of the yttria ceramics were investigated. The yttria ceramics sintered using SPS had higher bulk density and thermal shock resistance than the samples sintered using CS. When the sintering process for the ceramics sintered from needle-like yttria powder was switched from CS to SPS, the bulk density increased from 4.44 g·cm
to 5.01 g·cm
, while the number of thermal shock tests increased from two to six. The denser samples showed better thermal shock resistance, which may be related to the fracture mechanism shifting from intergranular fracture to transgranular fracture.
Binary ethosome vesicles have been developed as flexible lipid vesicles for the enhanced physicochemical stability and skin delivery of drugs. This work aimed to prepare phloretin-loaded propylene ...glycol ethosomes (PHL-PGEs) to improve their stability, skin permeability and antioxidant activity. PHL-PGEs were prepared via the ethanol injection method and optimized using different weight ratios of ethanol to propylene glycol (PG). When the ethanol/PG mass ratio changed from 10:0 to 0:10, the encapsulation efficiency and stability of ethosomes increased. At a PHL concentration of 1mg/mL, the EE% was 89.42 ± 2.42 and the DL% was 4.21 ± 0.04, which exhibited their highest values. The encapsulation of the PHL in the PHL-PGEs was strengthened via XRD analysis and FTIR analysis. The results of the in vitro percutaneous permeability test demonstrated that the combined use of ethanol and PG exhibited a notable enhancement in skin permeability, and the skin retention of PHL-PGEs was 1.06 times that of PHL-ethosomes (PHL-Es) and 2.24 times that of the PHL solution. An in vitro antioxidant activity study indicated that solubility and antioxidant activity was potentiated via the nanoencapsulation of phloretin. Therefore, these results confirm the potential of this nanocarrier to enhance physicochemical stability, skin permeability and antioxidant activity.
Pseudorabies virus (PRV) is one of the causative agents of common infectious diseases in swine herds. Enterococcus faecium is a probiotic belonging to the group of lactic acid bacteria and has ...excellent immunomodulatory effects. Vaccine immunization is an important approach to prevent animal diseases in the modern farming industry, and good immunization outcomes can substantially reduce the damage caused by pathogens to animals, improve the quality of animals’ lives, and reduce economic losses. In the present study, we showed that inactivated E. faecium and inactivated PRV when co-injected intravenously significantly reduced the mortality of mice after inoculation with PRV. The inactivated E. faecium + inactivated PRV intravenous injection group induced more production of Th cells and Tc cells. Additionally, the inactivated E. faecium + inactivated PRV intravenous injection group showed higher concentrations of cytokines (IFN-γ and IL-10) and induced higher antibody production. Thus, the co-injection of inactivated E. faecium and inactivated PRV could remarkably prevent and control the lethality of PRV infection in mice, which is a critical finding for vaccination and clinical development.
In a high-speed railway (HSR) corridor, railway companies provide diverse train services with different features such as departure time, running speed, and fare. Furthermore, passengers have varying ...preferences, which influence their travel choices. Focusing on this problem, this paper proposed a novel train timetable optimization model based on departure time and pricing strategy to analyze their impact on passengers’ travel choices with a consistent operating speed. Additionally, an extended time-space-fare network is constructed to visualize this process. The generalized cost of each arc in the network is used as a criterion for evaluating passenger selection. Then, we adapted a passenger flow distribution method based on the user equilibrium (UE) principle to allocate the passenger flow to each train. We also developed a bi-level planning model with passenger allocation as the lower-level model and timetable decision as the upper-level one to optimize collaboratively. Finally, a genetic algorithm integrated with the Frank-Wolfe method is designed to seek the optimal timetable and pricing strategy and a concrete numerical example in Lanzhou-Xi’an HSR is taken to investigate the effectiveness of the proposed model and algorithm.
Breast cancer is one of the most common cancers worldwide among women, and angiogenesis has an important effect on its growth and metastasis. Glipizide, which is a widely used drug for type 2 ...diabetes mellitus, has been reported to inhibit tumor growth and metastasis by upregulating the expression of natriuretic peptide receptor A (NPRA). Atrial natriuretic peptide (ANP), the receptor of NPRA, plays an important role in angiogenesis. The purpose of this study was to explore the effect of glipizide combined with ANP on breast cancer growth and metastasis.
This study aimed at investigating the effect of glipizide combined with ANP on breast cancer. Glipizide, ANP, or glipizide combined with ANP was intraperitoneally injected into MMTV-PyMT mice. To explore whether the anticancer efficacy of glipizide combined with ANP was correlated with angiogenesis, a tube formation assay was performed.
Glipizide combined with ANP was found to inhibit breast cancer growth and metastasis in MMTV-PyMT mice, which spontaneously develop breast cancer. Furthermore, the inhibitory effect of ANP combined with glipizide was better than that of glipizide alone. ANP combined with glipizide significantly inhibited tube formation of human umbilical vein endothelial cells (HUVECs) by suppressing vascular endothelial growth factor (VEGF)/VEGFR2 (vascular endothelial growth factor receptor 2) signaling.
These results demonstrate that glipizide combined with ANP has a greater potential than glipizide alone to be repurposed as an effective agent for the treatment of breast cancer by targeting tumor-induced angiogenesis.
The development of a simple, portable and accurate instrument used in the evaluation of in vitro cytotoxicity is particularly important and urgent in the field of toxicology research at present. In ...the current study, a miniature electrochemical detection system was constructed that integrated graphene oxide quantum dots and multiwall carbon nanotubes modified anodized screen printed carbon electrode (GOQDs/MWCNTs/SPCE*) with a mini reaction vessel, which reduced the consumption of sample from 500 to 80 μL. Four electrochemical signals could be detected in cells distinctly for the first time which were attributed to the oxidation of uric acid, guanine/xanthine, adenine and hypoxanthine, respectively. This miniature electrochemical detection system has better selectivity, sensitivity and its detection limits were lower than those of most electrochemical sensors. Furthermore it has been found that the level of purine nucleotide metabolism in BALB/3T3 cells and MCF-7 cells was different, which could be related to the different purine nucleotide metabolisms of cancer cells and non cancer cells. The simple, portable and miniature electrochemical detection system could be used as a convenient instrument for toxicology detection.
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•A miniature electrochemical detection system was constructed that reduced the consumption of sample from 500 to 80 μL.•Four electrochemical signals attributed to UA, G/X, A and HX could be detected in cells for the first time.•The level of purine nucleotide metabolism in BALB/3T3 cells and MCF-7 cells has been found different.
Surges in sympathetic activity should be a major contributor to the frequent occurrence of cardiovascular events towards the end of nocturnal sleep. We aimed to investigate whether the analysis of ...hypnopompic heart rate variability (HRV) could assist in the prediction of cardiovascular disease (CVD). 2217 baseline CVD-free subjects were identified and divided into CVD group and non-CVD group, according to the presence of CVD during a follow-up visit. HRV measures derived from time domain analysis, frequency domain analysis and nonlinear analysis were employed to characterize cardiac functioning. Machine learning models for both long-term and short-term CVD prediction were then constructed, based on hypnopompic HRV metrics and other typical CVD risk factors. CVD was associated with significant alterations in hypnopompic HRV. An accuracy of 81.4% was achieved in short-term prediction of CVD, demonstrating a 10.7% increase compared with long-term prediction. There was a decline of more than 6% in the predictive performance of short-term CVD outcomes without HRV metrics. The complexity of hypnopompic HRV, measured by entropy-based indices, contributed considerably to the prediction and achieved greater importance in the proposed models than conventional HRV measures. Our findings suggest that Hypnopompic HRV assists the prediction of CVD outcomes, especially the occurrence of CVD event within two years.
Gullies of different scales and types have developed in the Loess Plateau, China. Differences in the amount of gully erosion influence the development, evolution, morphology, and spatial distribution ...of these gullies. The strengths of headward erosion on the gully shoulder line are used to dictate soil and water conservation measures. In this study, six typical loess landforms in the Loess Plateau were selected as sampling sites: Shenmu, Suide, Ganquan, Yanchuan, Yijun, and Chunhua, which respectively represent loess–aeolian and dune transition zones, loess hills, loess ridge hills, loess ridges, loess long-ridge fragmented tablelands, and loess tablelands. Using 5 m resolution digital elevation model data from the National Basic Geographic Information Database, a small representative watershed was selected from each sampling site to obtain elevation data on the terrain profiles of gully shoulder lines. Multifractal detrended fluctuation analysis (MF-DFA) was used to conduct statistical and comparative analysis of the elevation fluctuation characteristics of these profiles. The results show that MF-DFA is capable of detecting active gully erosion sites. Sites of active gully erosion are concentrated in Shenmu and Suide but more widely distributed in the other five sites. The results provide a scientific basis for small watershed management planning and the design of soil and water conservation measures.
We aimed to provide insight into differences in drug review decisions made by the US Food and Drug Administration's (FDA) accelerated approval (AA) pathway and the European Medicines Agency's (EMA) ...conditional marketing authorisation (CMA) pathway, and to add to the current knowledge base of drug approval processes.
This cross-sectional study thoroughly examines novel oncology drugs with dual approval through FDA AA and EMA CMA between 2006 and 2021. Statistical analysis was performed from June to July 2022.
The study examined the regulatory differences between regions for dually approved novel oncology drugs, including approval decisions, pivotal efficacy clinical trials, speed of review and postmarketing obligations.
During this time period, there was a difference in the use of the FDA AA and the EMA CMA (FDA: EMA: 41.2%: 70.0%, p<0.05). Of the 25 drugs approved by both the FDA AA and the EMA CMA, 22 (88.0%) of the regulatory decisions were based on the same pivotal clinical trials. But there were more differences in the requirements for postmarketing obligations, with the EMA's postmarketing obligations focusing on the efficacy and safety of the drug (EMA: FDA: 63.0%: 27.0%, p＜0.05) and the FDA's postmarketing obligations focusing more on the efficacy (FDA: EMA: 73.0%: 23.9%, p＜0.05). In addition, both the USA and EU had some postmarketing obligations completed beyond the schedule (30.4% and 19.2% in the USA and EU, respectively), with the longest delays lasting 3.7 years (0.2-3.7 years) and 3.3 years (0.04-3.3 years) in the USA and EU, respectively.
The FDA and EMA have different orientations and benefit-risk balance considerations in the use of AA or CMA. It is also the case that the shortcomings in the design and implementation of postmarketing studies have made it a challenge to obtain the evidence needed to confirm a drug's benefits.
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