Hepatocellular carcinoma (HCC) is a common malignancy associated with a high risk of recurrence and metastasis and a poor prognosis. Here, we examined the involvement of the pseudokinase Tribbles 1 (TRIB1), a scaffold protein associated with several malignancies, in HCC and investigated the underlying mechanisms. TRIB1 was upregulated in HCC tissues and cell lines in correlation with low levels of p53. TRIB1 gain and loss of function experiments indicated that TRIB1 promoted HCC cell viability concomitant with the downregulation of p53, and induced HCC cell migration, invasion, and epithelial-mesenchymal transition. TRIB1 was identified as a target of microRNA-23a (miR-23a), and miR-23a overexpression downregulated TRIB1 and upregulated p53 in HCC cells. Ectopic expression of TRIB1 upregulated β-catenin and its effectors c-myc and MMP-7 in a p53-dependent manner. TRIB1 silencing inhibited tumor growth and promoted apoptosis in vivo via a mechanism that would involve the modulation of p53 and β-catenin signaling. The present results indicate that TRIB1 promotes HCC tumorigenesis and invasiveness via a feedback loop that involves the modulation of its expression by miR-23a with the likely downregulation of p53, and suggest the involvement of the β-catenin signaling pathway. These findings suggest potential targets for the treatment of HCC and therefore merit further investigation.
Rural residents’ perception is an important way of evaluating rural ecosystem services. Different topographies affect the level of ecosystem services, thus affecting residents’ perceived preferences. This study conducted a questionnaire survey of 1176 rural residents in mountainous, hilly, and plain areas of Shandong Province. It analyzed respondents’ satisfaction with ecosystem services and landscape preferences in different topographical areas. The results showed that the perception of ecosystem services was higher than average in all three topographic areas. The perceptions from high to low were cultural services, provisioning services, and regulating services. The perception of ecosystem services was significantly affected by topography, with significant differences between mountainous and plain areas in particular. Rural residents’ perceptions of cultural services varied widely and there were diverse preferences. This study believes that the important concerns in enhancing the perception of ecosystem services among rural residents are to raise villagers’ ecological awareness by meeting their growing spiritual needs and the high sensitivity of older people.
BACKGROUND: Knee osteoarthritis is a common degenerative joint disease where a single treatment method often fails to fully alleviate symptoms. Hence, finding effective non-invasive combined treatment approaches is particularly crucial. OBJECTIVE: The efficacy of treating knee osteoarthritis with hip abductors exercise training combined with repetitive transcranial magnetic stimulation was assessed through functional scales and objective evaluation methods. METHODS: In this four-week randomized clinical trial, 160 patients meeting inclusion criteria were randomly assigned 1:1 to group A to receive oral celecoxib and group B to receive a combination of hip abductors exercise training and repeated transcranial magnetic stimulation. The primary outcome was the western Ontario and McMaster universities osteoarthritis index. The secondary outcomes include Visual Analogue Scale, knee outcome survey activities of daily living scale, Active Range of Motion, and the Quadriceps Angle, the tibiofemoral angle, peak adductor moment, the integrated electromyography and root mean square of the surface electromyography of the lower extremity muscles. Paired sample t test was used for Within-Group comparison of outcome indicators, and independent sample t test was used for Between-Group comparison. RESULTS: Of the 160 randomly assigned patients, 150 completed the study. After 4 weeks, the WOMAC index decreased from 61 ± 10.83 to 40.55 ± 7.58 in the combined treatment group and from 60.97 ± 10.18 to 47.7 ± 10.13 in the celecoxib group. The effect of the combined treatment group was significantly higher than that in the celecoxib group (P< 0.001). In the combined treatment group, the score of knee joint daily living scale increased (P< 0.001), the active range of motion increased (P< 0.001), the quadriceps angle decreased (P< 0.001), the tibiofemoral angle increased (P< 0.001), and the peak adduction moment decreased (P< 0.001), integrated electromyography and root mean square increased (P< 0.001), and the effect was better than that of celecoxib group (P< 0.001). The visual analog scale score in celecoxib group was lower (P< 0.001) and knee outcome survey activities of daily living scale was higher (P< 0.001). The incidence of treatment-related adverse events was 10% in the celecoxib group and 2.5% in the combined treatment group, all of which were mild. CONCLUSIONS: Hip abductors exercise training combined with repetitive transcranial magnetic stimulation can enhance abduction muscle strength, improve mobility, reduce joint pain, and enhance quality of life. This combined approach shows superior clinical effectiveness compared to oral celecoxib.
The computer aided 3D display system, flicker-free field sequential stereoscopic image display system, is newly developed. This system is composed of personal computer, liquid crystal glasses driving card, stereoscopic display software and liquid crystal glasses. It can display field sequential stereoscopic images at refresh rate of 70 Hz to 120 Hz. A typical application of this system, 3D vision test system, is mainly discussed in this paper. This stereoscopic vision test system can test stereoscopic acuity, cross disparity, uncross disparity and dynamic stereoscopic vision quantitatively. We have taken the use of random-dot- stereograms as stereoscopic vision test charts. Through practical test experiment between Anaglyph Stereoscopic Vision Test Charts and this stereoscopic vision test system, the statistical figures and test result is given out.
The study of long-term changes to urban green space reveals the reasons for changes in the spatial pattern of urban green space and predicts the future development trends, which is of great importance for urban green space protection and integrated urban development. This study used Markov Chain and PLUS models to explore the spatial and temporal patterns of changes to green space in urban and rural areas in Jinan City during recent rapid urbanization and the driving forces behind them. The results show that from 2000 to 2020, the decrease in urban green space in Jinan City slowed down gradually, and that elevation and population density were the primary factors influencing changes in urban green space. In the simulation projections, the ecologically protected development scenario had a relatively low rate of site change and was more protective of arable land and green space. Ecological conservation development was predicted to result in a decrease in unused urban land and to reflect the advantages of intensive land use. The findings will provide decision-makers with ideas related to the sustainable development of urban green space.
Background Observational studies have documented increased serum IL-6 levels in elderly individuals afflicted with sarcopenia. Nevertheless, the relationship between serum IL-6 concentrations and sarcopenia prevalence in the aging population is yet to be defined.
ABSTRACT Molecular chirality plays a crucial role in the fields of chemistry and biology. Various nuclear magnetic resonance (NMR) methods have been employed for assignment of stereochemical configurations. Alignment media for measurements of anisotropic parameters contribute to configuration elucidations, while chiral auxiliaries assist in enantiomer discrimination and chiral recognition. However, each method comes with limitations, and the assignment of absolute configuration by NMR remains challenging. In this study, we explored a combined approach for absolute configuration elucidation with the multifaceted application of the oligopeptide (FK) 4 , which possesses dual functionalities as an alignment medium for anisotropic NMR measurements and a chiral differentiating agent. As an alignment medium, (FK) 4 facilitates the analysis of stereochemical features through residual dipolar couplings (RDC), aiding in the structural elucidation of stereoisomers. Moreover, (FK) 4 exhibits unique chiral differentiating properties, interacting distinctly with enantiomers and resulting in observable bifurcation of chemical shift signals, in 13 C, 1 H and 19 F spectra. Using isoleucine and xylose as model compounds, we demonstrate how the dual functionality of (FK) 4 enables the identification of stereoisomeric structures via RDC parameters and the assignment of enantiomeric configurations through measurements of t2 relaxation time coupled with theoretical simulations. These findings highlight the potential of versatile chiral media as (FK) 4 for approaching the elucidation of absolute configurations of organic molecules via combined NMR spectroscopy approaches, with implications for structural characterization and enantiomer discrimination in chemical applications.
Hydroxy-carboxylic acid receptors HCA1, HCA2, and HCA3 can be activated by important intermediates of energy metabolism. Despite the research focusing on HCA2, its clinical application has been limited by adverse effects. Therefore, the role of HCA1 as a promising target for the treatment of lipolysis warrants further exploration. As HCAs exhibit high similarity when activated with diverse selective agonists, a conserved yet unique activation mechanism for HCAs remains undisclosed. Herein, we unveil the cryo-electron microscopy structures of the 3,5-DHBA-HCA1-Gi signaling complex, the acifran- and MK6892-bound HCA2-Gi signaling complexes, and the acifran-HCA3-Gi signaling complex. Comparative analysis across HCAs reveals key residues in HCA1 contributing to the stabilization of the ligand-binding pocket. Furthermore, chimeric complexes and mutational analyses identify residues that are pivotal for HCA2 and HCA3 selectivity. Our findings elucidate critical structural insights into the mechanisms of ligand recognition and activation within HCA1 and broaden our comprehension of ligand specificity binding across the HCA family.
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