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Objective: To analyze effects of tectorigenin on improving cognitive deficits in rats with vascular dementia (VD) by regulating Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: A total of 72 rats were randomly divided into sham operation group, model group, low, medium and high doses [25, 50, 100 mg/(kg⋅d)] tectorigenin groups and positive control group [piracetam 324 mg/(kg⋅d], with 12 rats in each group. Except for sham operation group, VD models were replicated in other groups. After successful modeling, different doses tectorigenin groups and positive control group were administered intragastrically with different doses of tectorigenin and piracetam, while other groups were administered intragastrically with same volume of normal saline for 28 d. Spatial learning and memory ability were detected by Morris water maze. Neurotransmitter levels in hippocampus interstitial fluid were detected by high performance liquid chromatography-electro-chemical. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor b (TrkB) expressions in hippocampus were detected by RT-qPCR and Western blot. TLR4/MyD88/NF-κB pathway-related proteins in hippocampus were detected by Western blot. Results: Compared with sham operation group, escape latency was longer, while stay time in target area and times of crossing platform were lower in model group (P<0.05). Compared with model group, escape latency was shorter, while stay time in target area and times of crossing platform were higher in medium and high doses tectorigenin groups (P<0.05). NE, DA, 5-HT and 5-HIAA levels in model group were lower than those in sham operation group (P<0.05), which were higher in medium and high doses tectorigenin groups than model group (P<0.05). Compared with sham operation group, BDNF and TrkB mRNA and proteins levels were lower, while TLR4, MyD88 and p-NF-κB p65/NF-κB p65 proteins levels were higher in model group (P<0.05). Compared with model group, BDNF and TrkB mRNA and proteins levels were higher, while TLR4, MyD88 and p-NF-κB p65/NF-κB p65 proteins levels were lower in medium and high doses tectorigenin groups (P<0.05). Conclusion:Tectorigenin can improve cognitive deficits in VD rats, which may be related to regulating TLR4/MyD88/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

This paper addresses the substitution elasticity of capital on the labour force in the context of the development of intellectualization. Given the substitution of capital for labour, China's benchmark listed logistics companies are compared with an American company to discuss the evolution of capital – labour substitution. A large-scale intellectualization process began in 2017, and based on a variable elasticity of substitution, this paper creates an econometric model of substitution elasticity between capital and labour and its evolution between 2017 and 2021. The American logistics company UPS maintains a relatively high level of substitution elasticity, and Chinese logistics companies are quickly catching up. The substitution elasticity of capital on labour in Chinese enterprises trends upward year after year. In 2021, the capital – labour substitution elasticity of logistics enterprises in both countries showed considerable growth. The calculation model of substitution elasticity presented in this paper can be extended to different regions and industries to measure intelligent development levels and the relationship between capital and the labour force. [ABSTRACT FROM AUTHOR]

RAGE, a druggable inflammatory receptor, is known to function as an oligomer but the exact oligomerization mechanism remains poorly understood. Previously we have shown that heparan sulfate (HS) plays an active role in RAGE oligomerization. To understand the physiological significance of HS-induced RAGE oligomerization in vivo, we generated RAGE knock-in mice (AgerAHA/AHA) by introducing point mutations to specifically disrupt HS-RAGE interaction. The RAGE mutant demonstrated normal ligand-binding but impaired capacity of HS-binding and oligomerization. Remarkably, AgerAHA/AHA mice phenocopied Ager−/− mice in two different pathophysiological processes, namely bone remodeling and neutrophil-mediated liver injury, which demonstrates that HS-induced RAGE oligomerization is essential for RAGE signaling. Our findings suggest that it should be possible to block RAGE signaling by inhibiting HS-RAGE interaction. To test this, we generated a monoclonal antibody that targets the HS-binding site of RAGE. This antibody blocks RAGE signaling in vitro and in vivo, recapitulating the phenotype of AgerAHA/AHA mice. By inhibiting HS-RAGE interaction genetically and pharmacologically, our work validated an alternative strategy to antagonize RAGE. Finally, we have performed RNA-seq analysis of neutrophils and lungs and found that while Ager−/− mice had a broad alteration of transcriptome in both tissues compared to wild-type mice, the changes of transcriptome in AgerAHA/AHA mice were much more restricted. This unexpected finding suggests that by preserving the expression of RAGE protein (in a dominant-negative form), AgerAHA/AHA mouse might represent a cleaner genetic model to study physiological roles of RAGE in vivo compared to Ager−/− mice.

Abstract Background Dysfunction in brain network dynamics has been found to correlate with many psychiatric disorders. However, there is limited research regarding resting electroencephalogram (EEG) brain network and its association with cognitive process for patients with methamphetamine use disorder (MUD). This study aimed at using EEG microstate analysis to determine whether brain network dynamics in patients with MUD differ from those of healthy controls (HC). Methods A total of 55 MUD patients and 27 matched healthy controls were included for analysis. The resting brain activity was recorded by 64-channel electroencephalography. EEG microstate parameters and intracerebral current sources of each EEG microstate were compared between the two groups. Generalized linear regression model was used to explore the correlation between significant microstates with drug history and cognitive functions. Results MUD patients showed lower mean durations of the microstate classes A and B, and a higher global explained variance of the microstate class C. Besides, MUD patients presented with different current density power in microstates A, B, and C relative to the HC. The generalized linear model showed that MA use frequency is negatively correlated with the MMD of class A. Further, the generalized linear model showed that MA use frequency, scores of Two-back task, and the error rate of MA word are correlated with the MMD and GEV of class B, respectively. Conclusions Intracranial current source densities of resting EEG microstates are disrupted in MUD patients, hence causing temporal changes in microstate topographies, which are correlated with attention bias and history of drug use.

AIM: To preliminarily test proteomics in aqueous humor in patients with dry age-related macular degeneration (AMD) by using the proteomic technology. METHODS: Aqueous humor samples were collected from patients with or without dry AMD, who underwent cataract surgery. The aqueous samples were analyzed with isobaric tags for relative and absolute quantification (iTRAQ) combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) technology. The differential expressed proteins were analyzed with gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analysis. The data were partly validated by ELISA and Western blot. False discovery rate (FDR) was used for statistical analysis. RESULTS: A total of 244 proteins were detected, in which 38 proteins were up-regulated and 51 were down-regulated significantly in patients with dry AMD compared with that in control groups (FDR value

Background: This study aimed to share the experience in applying the chimney graft technique combined with embolization for treating aortic arch rupture under emergency conditions and evaluating early-term results in these patients.Methods: This study retrospectively included patients with ruptured aortic arch lesions who received the chimney graft technique combined with embolization between March 2016 and March 2021. The primary endpoint was a technical success, deemed as successful stent graft deployment to the planned location, patency of the target branch vessel, and absence of significant type I endoleak. The secondary endpoint was clinical success defined with the size of false lumen in follow-up remaining unchanged or decreasing over time, 30-day mortality, complication, and primary patency of chimney graft.Results: This study included 12 patients (age, 61 ± 12 years; male, 83%). Five patients (42%) received single chimney, one patient (8%) received double chimney, and six patients (50%) received triple chimney. Intraoperative type I endoleak occurred in six patients (50%) who underwent endovascular embolization in the primary operation. Post-operative type I endoleak, evaluated by computed tomography angiography examination following the primary operation, occurred in seven patients (58%), including one patient who received endovascular embolization two times. All patients with post-operative type I endoleak were successfully re-treated using coil and Onyx glue within 1 week, and the median length of stay was 22 ± 11 days (range: 7–44 days). Overall technical success was 100%. Eleven patients had completed their follow-up (median, 12 months, range: 1–34 months), and one patient was out of contact. The 30-day mortality was 9% (1/11, post-operative death of a patient with cerebral hemorrhage). No major complications and no chimney compression, migration, occlusion, or stenosis were recorded during follow-up. Seven patients (58%) have ≥6 months of clinical follow-up time with appropriate imaging. In four (57%) of these patients, diameter stabilization was detected, whereas three (43%) experienced significant reduction (≥5 mm).Conclusion: The patients in this study had satisfactory early-term outcomes. The chimney graft technique combined with coil and Onyx glue embolization may be a safe and effective treatment for ruptured aortic arch lesions under emergency conditions.