The present study was designed to explore the biological role of resveratrol (RES) in rheumatoid arthritis (RA) and the underlying mechanism. The adjuvant‐induced arthritic rats were administered RES ...on the 12th day after model establishment, and then arthritis assessment, oxidative stress measurement, histological examination, and immunohistochemical staining were performed. The primary rat fibroblast‐like synoviocytes (FLS) were isolated and treated with RES in vitro and then cell proliferation and apoptosis assay were examined. Chromatin immunoprecipitation assay, luciferase reporter assay, intracellular reactive oxygen species (ROS) determination, western blot, and quantitative real time‐polymerase chain reaction (qRT‐PCR) were performed to investigate the mechanisms. RES administration decreased arthritis scores and serum levels of antioxidant enzymes, attenuated paw swelling, synovial hyperplasia, inflammatory cell infiltration, and cartilage degradation, as well as inhibited synoviocyte proliferation in synovial tissues. Further investigation indicated that RES inhibited ROS production and FLS proliferation through activating the silent information regulator 1 (SIRT1)/nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling pathway. NF‐κB was confirmed to negatively regulate miR‐29a‐3p and miR‐23a‐3p expression by directly binding to its promoter. Mechanistic analyses further revealed that Kelch‐like erythroid cell‐derived protein with CNC homology (ECH)‐associated protein 1 (Keap1), a negative regulator of Nrf2, was a downstream target of miR‐29a‐3p, while miR‐23a‐3p directly targeted cullin3 (cul3), a master regulator of ubiquitination and degradation of Nrf2. Together, the present study provided evidence that RES ameliorated RA through activation of Nrf2‐ARE signaling pathway via SIRT1/NF‐κB/miR‐29a‐3p/Keap1 and SIRT1/NF‐κB/miR‐23a‐3p/cul3 signaling pathway.
•Constructed a modelling framework for dynamic matching of supply and demand for urban ES.•Quantified supply and demand indicators based on the diversity and variability of demand for ES.•Identified ...an overall mismatch between supply and demand of green infrastructure in central Tianjin.•Proposed a sustainable development strategy for green spatial systems with multiple benefits.
Quantitative research on the supply and demand of urban green infrastructure (GI) ecosystem services (ES) can play a crucial role in supporting ecological governance, which is vital for enhancing the health and well-being of residents and promoting sustainable development. However, current supply and demand studies often fail to consider the complexity and diversity of local climates and economic status, leading to suboptimal outcomes in urban greening programs. Therefore, there is an urgent need to incorporate the diversity and variability of demand for ES in decision-making processes for urban GI planning. To address this issue, this study proposes a multi-development scenario-based supply and demand modelling framework that measures the supply and demand of ES. By using the central city of Tianjin, China, as a case study, the resulting GI construction potential zoning and optimization strategies are determined to achieve the multiple environmental-social-economic benefits of GI. The results show that the supply and demand levels of GI in the study area are significantly spatially heterogeneous, with the demand levels of GI varying considerably under different development scenarios. Furthermore, the demand for GI is highest under the ecological priority scenario. Based on the relationship between the supply and demand of ES, the study area is classified into four zones, including a GI supply deficit zone, a supply surplus zone, a low-level balance zone, and a high-level balance zone. The area of each zone decreases in turn, indicating that the study area as a whole is in a state of mismatch between the supply and demand of ES. Finally, the study area is divided into seven GI construction potential zones based on the degree of scarcity and development orientation. The proposed planning scheme helps to achieve dynamic matching goals of ES supply and demand and provides valuable insights for policymakers to coordinate urban resources and promote sustainable development.
We develope a computationally efficient extension of the Dyson Brownian Motion (DBM) algorithm to generate random function in C{sup 2} locally. We further explain that random functions generated via ...DBM show an unstable growth as the traversed distance increases. This feature restricts the use of such functions considerably if they are to be used to model globally defined ones. The latter is the case if one uses random functions to model landscapes in string theory. We provide a concrete example, based on a simple axionic potential often used in cosmology, to highlight this problem and also offer an ad hoc modification of DBM that suppresses this growth to some degree.
Tumor‐infiltrating immune cells play a crucial role in tumor progression and response to treatment. However, the limited studies on infiltrating immune cells have shown inconsistent and even ...controversial results for osteosarcoma (OS). In addition, the dynamic changes of infiltrating immune cells after neoadjuvant chemotherapy are largely unknown. We downloaded the RNA expression matrix and clinical information of 80 OS patients from the TARGET database. CIBERSORT was used to evaluate the proportion of 22 immune cell types in patients based on gene expression data. M2 macrophages were found to be the most abundant immune cell type and were associated with improved survival in OS. Another cohort of pretreated OS samples was evaluated by immunohistochemistry to validate the results from CIBERSORT analysis. Matched biopsy and surgical samples from 27 patients were collected to investigate the dynamic change of immune cells and factors before and after neoadjuvant chemotherapy. Neoadjuvant chemotherapy was associated with increased densities of CD3+ T cells, CD8+ T cells, Ki67 + CD8+ T cells and PD‐L1+ immune cells. Moreover, HLA‐DR‐CD33+ myeloid‐derived suppressive cells (MDSC) were decreased after treatment. We determined that the application of chemotherapy may activate the local immune status and convert OS into an immune “hot” tumor. These findings provide rationale for investigating the schedule of immunotherapy treatment in OS patients in future clinical trials.
Host anti–tumor immune response boosted by neoadjuvant chemotherapy. Following neoadjuvant chemotherapy, CD3+ T cells increased significantly and there was a trend of increased cytotoxic T cells. CD8+ T cells in both tumor center and stroma also increased remarkably. Importantly, activated CD8+ T cells, defined as Ki67 + CD8+ T cells, were more abundant in post–chemotherapy samples, and were negatively correlated with the proliferation ability of tumor cells.
Wetlands form a crucial component of ecosystems, and wetland restoration serves as an effective strategy for promoting sustainable urban development. Spatial support is essential for wetland ...restoration, meaning that research on wetland spatial planning is of considerable importance. Existing studies on wetland spatial planning primarily focus on the analysis of wetland spatial distribution characteristics, with limited exploration of wetland spatial relationships. This paper aims to explore the potential of utilizing both spatial distribution characteristics and spatial relationships to identify wetland spatial issues, thereby facilitating the formulation of wetland spatial planning strategies. Using Tianjin City as a case study, this research applies nearest neighbor analysis, the geographic concentration index, the Gini index, and kernel density analysis to identify the spatial distribution characteristics of wetlands in Tianjin. Additionally, spatial autocorrelation analysis and connectivity analysis are employed to identify the interrelationships among wetlands in Tianjin. Based on the results derived from the analysis of spatial distribution characteristics and spatial relationships, wetland spatial planning strategies are proposed. The effectiveness of these strategies is validated using methods that consider both spatial distribution characteristics and spatial relationships. The findings reveal that, although wetlands in Tianjin are widely distributed, large wetland patches are primarily concentrated in areas with abundant water resources, while the six districts within the city have few or no large patches of wetlands. The spatial distribution of wetlands is highly uneven, exhibiting patterns of high–high aggregation and low–low aggregation. The number of connecting paths between wetland patches is relatively low, indicating a generally low overall connectivity. While medium-sized and larger wetland patches maintain the connectivity of existing wetlands in Tianjin, small wetlands that serve as stepping stones are lacking. Following the implementation of planning strategies, there would be an increase in the wetland area in Tianjin, accompanied by significant improvements in the spatial distribution pattern and spatial relationships of the wetlands.
This paper analyzes the characteristics of convective heat transfer of a pulse-heated platinum microwire cooling in CO2 under supercritical pressures based on experimental data. The microwire ...undergoes a rapid temperature rise of around 664 K within 0.35 ms. An inverse problem is formulated and numerically solved to extract heat transfer data from experimental measurements. In addition, a predictive model for the convective heat transfer coefficient is developed to fully close the equation set. Results are interpreted based on the bulk pressure from 7.38 to 9 MPa and bulk temperature from 295 to 325 K. The convective heat flux of CO2 generally decreases with time, and in the medium-term, the reduction is slightly decelerated owing to buoyancy-driven flows. This demonstrates that high-pressure and low-temperature bulk states generally exert larger convective heat flux to cool the microwire. During the early 10 ms, the time-averaged convective heat flux is of the order of 1 MW/m2, resulting in rapid cooling. This value shows a weak critical enhancement upon crossing the Widom line. During the remaining time, the time-averaged convective heat flux drops to the order of 0.1 MW/m2. Such a drop in heat flux is more obvious in low-bulk-density cases, leading to a relatively long time for sufficient W cooling.
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by symmetrical polyarthritis as its main clinical manifestation. Uncontrolled RA eventually leads to joint deformities and ...loss of function. Currently, the pathogenesis of RA remains under discussion, and RA treatment is still at the bottleneck stage. Resveratrol has long been regarded as a potential antioxidant drug for RA treatment. Currently, resveratrol is considered to exert therapeutic effects on RA by activating silent information regulator 1 (SIRT1) and its downstream pathways. There is notable crosstalk between the SIRT1 and NF-κB pathways, and these pathways, which play an essential role in the development of RA, are unexpectedly linked to the influence of resveratrol. Based on recent studies of almost all the pathways that resveratrol can affect, this review summarizes a regulatory chain of core components that cover multiple tracks. We also list the effects of resveratrol on immune cells and other subtle controls, which can help clinicians understand the known mechanism of resveratrol and better treat patients with RA.
Thyroid dysfunction is associated with abnormal glucose-insulin homeostasis, and the triglyceride-glucose (TyG) index has been recommended as a convenient surrogate of insulin resistance (IR). This ...study aimed to investigate the relationship between TyG and thyroid function in the US population.
We analyzed data from the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2012 in a cross-sectional manner. Aside from conventional thyroid parameters, our study evaluated the central sensitivity to thyroid hormones (THs) using the thyroid feedback quantile-based index (TFQI), thyrotropin resistance index (TT4RI), and thyrotropin index (TSHI). To evaluate peripheral sensitivity to THs, we calculated the ratio of free triiodothyronine (FT3) to free thyroxine (FT4) and the sum activity of peripheral deiodinases (SPINA-GD). In the 1848 adults, multivariable linear regression, subgroup, and interaction analyses were employed to estimate the association between TyG and thyroid parameters. The nonlinear relationship was addressed by smooth curve fittings and generalized additive models.
After adjusting covariates, we demonstrated a significant negative association between TyG and FT4 (β = - 0.57, p < 0.001), and a positive relationship between TyG and thyroid-stimulating hormone (β = 0.34, p = 0.037), as well as TgAb (β = 17.06, p = 0.005). Subgroup analysis indicated that the association between TyG and TgAb was more pronounced in the female subjects (β = 32.39, p < 0.001, p for interaction = 0.021). We also confirmed an inverse correlation between TyG and central sensitivity to THs, as assessed by TSHI and TT4RI (βTSHI = 0.12, p < 0.001; βTT4RI = 2.54, p = 0.023). In terms of peripheral sensitivity to THs, we found a significant positive correlation between TyG and FT3/FT4 (β = 0.03, p = 0.004), and SPINA-GD (β = 2.93, p = 0.004).
The present study established a noteworthy association between TyG and thyroid parameters, indicating a strong link between IR and thyroid dysfunction. Further investigations are warranted to validate these results.
Accurately identifying the boundary of urban clusters is a crucial aspect of studying the development of urban agglomerations. This process is essential for comprehending and optimizing smart and ...compact urban development. Existing studies often rely on a single category of data, which can result in coarse identification boundaries, insufficient detail accuracy, and slight discrepancies between the coverage and the actual conditions. To accurately identify the extent of urban clusters, this study proposes and compares the results of three methods for identifying dense urban areas of three major agglomerations in China: Beijing–Tianjin–Hebei, the Yangtze River Delta, and the Guangdong–Hong Kong–Macao Greater Bay Area. The study then integrates the results of these methods to obtain a more effective identification approach. The social economic method involved extracting a density threshold based on the fused nuclear density of socio-economic vitality data, including population, GDP, and POI, while the remote sensing method evaluated feature indices based on remote sensing images, including the density index, continuity index, gradient index, and development index. The traffic network method utilizes land transportation networks and travelling speeds to identify the minimum cost path and delineate the boundary by 20–30 min isochronous circles. The results obtained from the three methods were combined, and hotspots were identified using GIS overlay analysis and spatial autocorrelation analysis. This method integrates the multi-layered information from the previous three methods, which more comprehensively reflects the characteristics and morphology of urban clusters. Finally, the accuracy of each identification result is verified and compared. The results reveal that the average overall accuracy (OA) of the three areas delineated by the first three methods are 57.49%, 30.88%, and 33.74%, respectively. Furthermore, the average Kappa coefficients of these areas are 0.4795, 0.2609, and 0.2770, respectively. After performing data fusion, the resulting average overall accuracy (OA) was 85.34%, and the average Kappa coefficient was 0.7394. These findings suggest that the data fusion method can effectively delineate dense urban areas with greater accuracy than the previous three methods. Additionally, this method can accurately reflect the scope of urban clusters by depicting their overall boundary contour and the distribution of internal details in a more scientific manner. The study proposes a feasible method and path for the identification of urban clusters. It can serve as a starting point for formulating spatial planning policies for urban agglomerations, aiding in precise and scientific control of boundary growth. This can promote the rational allocation of resources and optimization of spatial structure by providing a reliable reference for the optimization of urban agglomeration space and the development of regional spatial policies.
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