Search

Purpose: COVID-19 viral infection results in dysregulation of the complement system and a decrease in cortisol and adrenocorticotropin hormone (ACTH) levels. This study aimed to explore the complement system, as well as cortisol and ACTH responses in patients with post-COVID-19 conditions (PCC) and type 2 diabetes mellitus (T2DM). Patients and Methods: This study recruited 31 patients with PCC and T2DM (PCC-T2DM), 19 patients with PCC (PCC), 10 patients with T2DM (T2DM), and 10 healthy participants (control). Cortisol and ACTH in the PCC and PCC-T2DM groups were assessed using the insulin tolerance test. In the fasting state, serum samples were collected for proteomic analyses. Spearman correlation analysis was performed between proteins and cortisol, as well as between proteins and ACTH. Results: Cortisol and ACTH levels were consistently decreased in the PCC and PCC-T2DM groups. Proteomic analyses revealed that most of the differentially abundant proteins (DAPs) in the PCC vs control and PCC-T2DM vs T2DM were involved in the coagulation and complement cascade, and the essential complement C3 was significantly upregulated in the PCC and PCC-T2DM groups when compared to their controls. Additionally, complement-related DAPs in the PCC vs control and PCC-T2DM vs T2DM were significantly correlated with cortisol and ACTH levels. In comparing PCC-T2DM samples with PCC samples, we found that upregulated DAPs were linked to the complement system and other immune system, and most DAPs were negatively correlated with cortisol and ACTH. Conclusion: Our study revealed that T2DM exacerbated dysregulation of the complement system in patients with PCC, and significant correlations were present between complement protein levels and those of cortisol and ACTH. These results provide novel insights into the dysregulation of complement and endocrine hormones in patients with PCC and T2DM. [ABSTRACT FROM AUTHOR]

In China, in recent years it has become a prevailing trend to promote the spatial maturity and high-quality transformation of new towns, yet there are few quantitative methods to evaluate their urban morphological maturity. From the perspective of quantitative urban morphology, this paper integrates street view data and cutting-edge analytical techniques into classic urban morphological study and develops a quantitative index for evaluating urban morphological maturity that fits Chinese cities by adjusting the indicators in line with the unique characteristics of the built environment of Chinese cities. Focusing on five new towns, as well as a historic area, of Shanghai, the paper evaluates their urban morphological maturity with this quantitative index and verifies its validity by comparing the evaluation result with that of expert consensus. It then proposes some design guidelines that may provide robust support for the regeneration of these new towns. Given its reliance on the multi-source data of open access and ready availability, this index holds promise for evaluating the urban morphological maturity of other new towns, to provide support for urban form improvement from both holistic and detailed perspectives. [ABSTRACT FROM AUTHOR]

Rationale: Proteomics and metabolomics are widely used in the study of diabetes, but rarely in prediabetes research. This study aimed to explore the mechanisms of early‐onset type 2 diabetes mellitus (T2DM) by analyzing proteomic changes at different stages of glucose metabolism. Methods: A total of 40 individuals undergoing routine physical health examinations between December 2016 and April 2017 were enrolled. Subjects were divided into four groups based on fasting blood glucose (FPG) levels: FPG < 5.6 mmol/L (group A); FPG ≥ 5.6 mmol/L and <6.1 mmol/L (group B); FPG ≥ 6.1 mmol/L and <7.0 mmol/L (group C); and FPG ≥ 7.0 mmol/L (group D). Each group had 10 cases. Sera from these 40 subjects were analyzed by label‐free quantitative liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). LC/MS/MS with selected reaction monitoring mode was also performed for qualitative and quantitative metabolomics analysis. Differentially expressed proteins were identified. Partial least squares discriminant analysis (PLS‐DA) and orthogonal partial least squares discriminant analysis (OPLS‐DA) were used to analyze the differentially expressed metabolites. Results: A total of 202 differentially expressed proteins were screened and were identified as mainly secreted proteins. Comparing group A with group B, 32 proteins were up‐regulated and 18 proteins were down‐regulated. Comparing group A with group C, 24 proteins were up‐regulated and 24 proteins were down‐regulated. Comparing group A with group D, 19 proteins were up‐regulated and 17 proteins were down‐regulated. The fold change for up‐regulated proteins was >1.2, p < 0.05, while the fold change for down‐regulated proteins was <−1.2, p < 0.05. PLS‐DA and OPLS‐DA revealed 113 differentially expressed metabolites. Correlation analysis of differentially expressed metabolites of group A versus group B revealed that among the down‐regulated differential proteins, transforming growth factor β‐induced protein ig‐h3 correlated negatively with metabolite L‐saccharin, while among the up‐regulated differential proteins, apolipoprotein C‐IV correlated negatively with metabolite 3‐methyloxindole. Among all differentially expressed proteins, 19 proteins were associated with early initiation of chronic inflammation, including CD14 and CSF‐1R, which were newly identified in the early onset of T2DM. Conclusions: Many proteins are differentially expressed between prediabetes and after T2DM diagnosis, although the specific mechanism remains unclear. The expression level of CD14 was significantly up‐regulated and that of CSF‐1R was significantly down‐regulated when FPG was ≥5.6 mmol/L, suggesting that CD14 and CSF‐1R may be important markers for early‐onset T2DM and may serve as new targets for T2DM treatment. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency can damage the human immune system, and the complement system is a key component of the immune system. This study aimed to elucidate the mechanism by which vitamin D affects the immune system by analyzing the changes in the protein expression of the complement system under different vitamin D levels. We selected 40 participants and divided them into three groups according to their serum levels of 25-hydroxyvitamin D (25(OH)VD): group A, 25(OH)VD ≥ 40 ng/mL; group B, 30 ng/mL ≤ 25(OH)VD < 40 ng/mL; and group C, 25(OH)VD < 30 ng/mL. Serum samples were subjected to biochemical analysis, followed by proteomic analysis using high-throughput untargeted proteomic techniques. Vitamin D deficiency increased the levels of fasting blood sugar, fasting serum insulin, and homeostasis model assessment (HOMA) of insulin resistance and decreased the secretion of HOMA of β-cell function, which led to insulin resistance and glucose metabolism disorder. Moreover, vitamin D deficiency resulted in the abnormal expression of 56 differential proteins, among which the expression levels of complement factor B, complement component C9, inducible co-stimulator ligand, and peptidase inhibitor 16 significantly changed with the decrease in vitamin D content. Functional enrichment analysis of these differential proteins showed that they were mainly concentrated in functions and pathways related to insulin secretion and inflammation. In conclusion, vitamin D deficiency not only contributes to insulin resistance and glucose metabolism disorder but also causes abnormal protein expression, resulting in the abnormal activation of the complement system. This study provides a novel theoretical basis for further studies on the relationship between vitamin D and the immune system. [ABSTRACT FROM AUTHOR]

Transit-oriented development (TOD) construction is considered critical for economic growth and the population's daily well-being in suburban development. However, there are few empirical evaluations of TOD performance and typology in suburban areas of high-density cities. In this study, we selected 23 metro stations in the five new towns in Shanghai as research objects to understand their TOD characteristics. By proposing a data-driven framework built on points of interest (PoIs) to characterize urban functions of metro stations in new towns, four thematic topic functions were extracted by implementing Latent Dirichlet Allocation (LDA) topic modeling. Five types of stations were revealed through a hierarchical cluster analysis based on their main functions. Then, an extended "Node-Place" model with a third "design" dimension was applied to classify TOD typologies. After establishing an evaluation framework by calculating the results of 15 indicators, five TOD topologies were identified through hierarchical cluster analysis. In addition, results from the ANOVA analysis showed that the classification according to thematic topics changes according to the "place" dimension indicators. Ultimately, the identified urban thematic function types and TOD types provide a useful tool for planners and governors to diagnose common problems and design targeted strategies in new towns. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates the possible roles and potential prediction ability of metabolic parameters in the early development of T2D by detecting their serum levels at different fasting blood glucose (FBG) levels. Methods: The subjects were included and divided into normal glucose tolerance (NGT), prediabetes (PD), and T2Dsubgroups. Apart from detecting the levels of routine biochemical parameters, fasting serum insulin (FINS), 25(OH)D, thioredoxin-interacting protein (TXNIP), thioredoxin (TRX), and NOD-like receptor family, pyrin domain-containing 3 (NLRP3) were detected. β-cell dysfunction (HOMA-β) and insulin resistance (HOMA-IR) were assessed by homeostasis model assessment. Both univariate and multivariate logistic regression analyses were used to estimate the risk of metabolic parameters, and their optimal cut-off values were obtained in the receiver operating characteristic (ROC) curve analysis and the Youden index. Results: Among the 207 subjects, aged from 20 to 60 years (44.62+12.92) contain 118 males and 89 females. There was a significantly lower trend of TRX, HOMA-β, and 25(OH)D following the higher FBG level among these three subgroups, while a significantly higher trend of all the other metabolic parameters. The multivariate analysis showed that subjects with higher values of TRX, HOMA-β, and 25(OH)D had a significantly lower risk for patients to be diagnosed as PD (aOR: 0.945, 0.961, and 0.543) and T2D (aOR: 0.912, 0.947, 0.434). Under the reliable 95% CI, TXNIP with a cut-off value of 119.27 showed the highest AUC value, sensitivity, and specificity (AUC: 0.981, 95% CI: 0.8524– 0.9839, 91.49%, and 83.33%) to diagnose PD. FINS with a cut-off value of 28.1 also showed the highest ones (AUC=0.9872, 95% CI: 0.9753– 0.9992, 100%, and 92.91%) to diagnose T2D. Conclusion: Early prediction of T2D is vital for timely intervention. Based on the FBG ≥ 100.8 mg/dl, the results provide evidence that 25(OH)D might be the protective factor in the early development of T2D. Besides, TXNIP and FINS might be the predictor for PD and T2D, respectively. [ABSTRACT FROM AUTHOR]