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In-depth research on the spatial and temporal evolution of ecosystem service trade-offs and synergistic relationships, scientific identification of ecosystem service bundles, and the main factors affecting the spatial differentiation of ecosystem service bundle provisioning are crucial to enhancing the overall benefits of regional ecosystem services and human well-being. Based on the assessment of the Guangdong–Hong Kong–Macao Greater Bay Area ecosystem service functional system, we combined the correlation analysis method, hierarchical clustering method, and principal component analysis to analyze the trade-offs/synergistic relationships of 11 indicators contained in four major ecosystem service categories of the Guangdong–Hong Kong–Macao Greater Bay Area and explored the study of ecosystem service bundle identification and clustering spatial differentiation. The results of this study showed the following: (1) Between 2000 and 2018, Regulating and Supporting services showed a decreasing trend while provisioning and cultural services showed an increasing trend. Human interference affected the spatial differentiation of ecosystem services provision; the provision of individual ecosystem services was more random, but the geospatial distribution showed a certain degree of regularity. (2) The intrinsic connection of ecosystem services is continuously strengthened, and the other four ecosystem services except industrial products in the provisioning services easily produce synergistic relationships with regulating and supporting services, while industrial products, leisure and recreation, scientific research and education, and other ecosystem services are more likely to produce a trade-off relationship between them. The correspondence among ecosystem service trade-offs, synergistic relationships, and cold/hot spots is not uniform due to spatial scales. (3) The method of combining socio-economic statistics and the InVEST model can identify similar ecosystem service bundle classifications, but there are differences in the performance of some of the roles at different study scales and in different study areas. (4) For complex urban-natural ecosystem services, the classified ecosystem service bundles have broad similarities. The development of high-density city clusters depends on the coordinated development of the population, resources, environment, society, and economy of each city in the region. [ABSTRACT FROM AUTHOR]

Ancient trees play an important ecosystem service role in high-density cities, revealing the zonal distribution characteristics of vegetation under climate influence. The ancient trees in Guangzhou and Foshan in 2018 and 2023 were taken as study objects to explore the evolution of their spatio-temporal patterns and to analyze the spatial differentiation characteristics of their driving factors using the geographical weighted regression (GWR) model. The results showed the following: (1) The ancient trees in Guangzhou and Foshan were composed of typical subtropical evergreen broad-leaved forest communities, mainly represented by broad-leaved species of evergreen dicotyledonous plants. The dominant species mainly included Litchi chinensis, Ficus microcarpa, Canarium pimela, Ficus virens, and Dimocarpus longan. However, there was a significant difference between Guangzhou and Foshan. (2) The number of ancient trees in Guangzhou showed negative growth, while Foshan saw a significant increase. However, species diversity in both areas increased, with the highest diversity in the northeast, higher diversity in the south-central part, and lower diversity in the western and northwestern parts. (3) The maximum kernel density of ancient trees in Guangzhou and Foshan differed 22-fold, indicating a spatial distribution pattern of multiple clusters. (4) The GWR model effectively explained the driving factors of the heterogeneity of the spatial distribution of ancient trees. The results showed that artificial disturbance was the most important factor affecting the spatial distribution of ancient trees in high-density urban agglomerations in the same vegetation zone. The study clarified the characteristics of the spatial distribution and species diversity of ancient trees in the region, revealed the driving factors for the evolution of the spatial pattern of ancient trees in highly urbanized areas, and provided guidelines for policies and measures for enhancing biodiversity and conserving germplasm resources in the region. [ABSTRACT FROM AUTHOR]

To evaluate the pharmacokinetic effects of SHR3680 on repaglinide and bupropion and its metabolite hydroxybupropion. Methods: A single‐centre, open‐label, single‐arm, fixed‐sequence clinical trial in 18 patients with prostate cancer. Results: After a single oral dose of 0.5 mg repaglinide and SHR3680, geometric mean peak plasma concentration (Cmax) of plasma repaglinide was 14.240 and 5.887 ng/mL, geometric mean area under the concentration–time curve (AUC0–t)was 20.577 and 7.320 h ng/mL, geometric mean AUC0–∞ was 20.949 and 7.451 h ng/mL, mean half‐life (t1/2) was 1.629 and 1.195 hours, and geometric mean oral clearance (CL/F) was 23.867 and 67.107 L/h, respectively. After a single oral administration of 150 mg bupropion and SHR3680, geometric mean Cmax of plasma bupropion was 85.430 and 33.747 ng/mL, geometric mean AUC0–t was 1003.896 and 380.158 h ng/mL, geometric mean AUC0–∞ was 1038.054 and 401.387 h ng/mL, mean t1/2 was 22.533 and 17.733 hours, and geometric mean CL/F was 144.501 and 373.705 L/h, respectively. The plasma geometric mean Cmax of its main active metabolic hydroxybupropion was 268.113 and 177.318 ng/mL, geometric mean AUC0–t was 14 283.087 and 5420.219 h ng/mL, geometric mean AUC0–∞ was 15 218.158 and 5364.625 h ng/mL, mean t1/2 were 36.069 and 16.688 hours, and geometric mean CL/F was 8.623 L/h and 27.961 L/h, respectively. Conclusion: Coadministration of SHR3680 with repaglinide or bupropion significantly shortened the elimination half‐lives, significantly increased the apparent clearance rate, and significantly decreased the in vivo exposure of repaglinide, bupropion and hydroxybupropion compared with single administration of repaglinide or bupropion. [ABSTRACT FROM AUTHOR]

Solute carrier family 12 member 5 (SLC12A5) has an oncogenic role in bladder urothelial carcinoma. The present study aimed to characterize the molecular mechanisms of SLC12A5 in bladder urothelial carcinoma pathogenesis. Functional assays identified that in bladder urothelial carcinoma SLC12A5 interacts with and stabilizes SOX18, and then upregulates matrix metalloproteinase 7 (MMP7). In vivo and in vitro assays were performed to confirm the effect of SLC12A5's interaction with SOX18 on MMP7‐mediated bladder urothelial carcinoma progression. SLC12A5 was upregulated in human bladder tumors, and correlated with the poor survival of patients with bladder urothelial carcinoma tumor invasion and metastasis, promoted by SLC12A5 overexpression. We demonstrated that SLC12A5 interacted with SOX18, and then upregulated MMP7, thus enhancing tumor progression. Importantly, SLC12A5 expression correlated positively with SOX18 and MMP7 expression in bladder urothelial carcinoma. Furthermore, SLC12A5 expression was suppressed by miR‐133a‐3p. Ectopic expression of SLC12A5 partly abolished miR‐133a‐3p‐mediated suppression of cell migration. SLC12A5‐SOX18 complex‐mediated upregulation on MMP7 was important in bladder urothelial carcinoma progression. The miR‐133a‐3p/SLC12A5/SOX18/MMP7 signaling axis was critical for progression, and provided an effective therapeutic approach against bladder urothelial carcinoma. [ABSTRACT FROM AUTHOR]

Tissue engineering technology offers an appealing approach for tissue reconstruction of the urothelium. Adipose-derived mesenchymal stem cells (ADSCs) represent an abundant source for tissue engineering applications. However, ASCs primarily possess mesoderm lineage differentiation potential. It is difficult to induce differentiation of ASCs towards urothelial cells that are derived from the endoderm, although a recent findings have reported that a conditioned medium may drive ADSCs towards differentiation into the urothelium phenotype. In the present study, human ADSCs were isolated from abdominal adipose tissues and incubated in this conditioned medium for indicated time periods. Western blotting showed that protein expression levels of urothelial specific marks, including CK7, CK20 and UPIII, were increased after seven days' incubation, but immunofluorescence microscopy determined that cells with CK7 and UPIII staining were scarce, which suggested a low-efficiency for the differentiation. Prolonging the incubation time did not further increase CK20 and UPIII expression. Furthermore, miR-33a expression was increased with ADSC differentiation. Using synthetic miRNAs to mimic or inhibit the action of miR-33a revealed that miR-33a hinders the differentiation of ADSCs towards urothelial cells. Furthermore, luciferase reporter assay confirmed that β-catenin and transforming growth factor-β receptor (TGFR) are targets of miR-33a. Inhibition of miR-33a expression increased β-catenin and TGFR expression and improved the efficiency of ADSCs towards differentiation into the urothelium phenotype. The present novel finding suggests that miR-33 may be an important target in tissue engineering and regenerative medicine for urothelium repair. [ABSTRACT FROM AUTHOR]