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It is important to explore the effective approaches to prevent dry age-related macular degeneration (AMD). In this study, significantly decreased full-field electroretinograms wave amplitudes and disordered retina structures were detected in rat retinas of sodium iodate induced dry AMD model. Six a- and b-wave amplitudes and the antioxidant activities were significantly increased, and the outer nuclear layer thickness was significantly improved in the rat retinas treated with the combination of Lactobacillus fermentum NS9 (LF) and aronia anthocyanidin extract (AAE) compared with the model. The effects were much better than the treatment with AAE alone. The proteomics analysis showed the expressions of α-, β- and γ-crystallins were increased by 3–8 folds in AAE treated alone and by 6–11 folds in AAE + LF treatment compared with the model, which was further confirmed by immuno-blotting analysis. Analysis of gut microbial composition indicated that higher abundance of the genus Parasutterella and species P. excrementihominis was found in the AAE + LF treatment compared with the other groups. The results indicated that the combined treatment of AAE + LF is a potential way to prevent the retina degeneration which is significantly better than the AAE treated alone. [ABSTRACT FROM AUTHOR]

The spatial differences of efficiency and development level of regional tourism are evident, and the dynamic grasp of their spatiotemporal evolution characteristics and coupling coordination relationship is important to promote high-quality sustainable tourism development. Herein, we measured the tourism development level of 31 provincial units in China during 2000–2020, introduced the data envelopment analysis-based Malmquist productivity index to determine tourism efficiency, used exploratory spatiotemporal data analysis methods to explore the spatiotemporal dynamic characteristics of regional tourism differences and spatial structure, constructed a coupled coordination model of tourism efficiency and development level and analyzed their coupling excellence and synergistic consistency. The results were as follows: (1) The spatial differences of comprehensive tourism efficiency from 31 provinces were evident, and the average situation showed high and low distribution characteristics in the east and west, respectively. The interannual changes showed a fluctuating downward trend, with the scale efficiency playing a supporting role for comprehensive efficiency and technical efficiency playing an influencing and restraining role. (2) Less fluctuation existed in the local spatial structure of tourism efficiency and development level; the direction of dependence was more stable, tourism development level was slightly more volatile, and the spatial dependency direction changes were similar. The tourism efficiency of local structure competition posture was stronger than that of collaboration, with the tourism development level collaboration integration being stronger. (3) The local spatial structure of tourism development level was more stable, the relative position of provincial units was more difficult to change, tourism efficiency of local spatial structure was unstable, and provincial units exhibited a greater possibility of change. (4) Tourism efficiency and the scale of the overall coupling degree and coupling coordination gradually improved, with similar spatiotemporal values. The overall coupling degree and coupling coordination degree of tourism efficiency and development level gradually improved, with similar spatiotemporal heterogeneity and volatility of local evolution. The area with a higher value coupling coordination degree spread slower and more widely. [ABSTRACT FROM AUTHOR]

The tourism industry in China presents uneven tourism efficiency but deepening spatial associations; thus, tourism resources must be more rationally allocated. In this study, the highly efficient SBM model was used to measure the tourism environmental efficiency of 31 provinces in China. A spatial correlation network is then constructed based on the gravity model, and the structural characteristics and influencing factors of the network are analyzed. The results show that (1) the overall tourism environmental efficiency in China presents a fluctuating growth trend, with significantly higher values observed in the eastern region than in the central and western regions; moreover, the growth in efficiency in the eastern region has been relatively stable in recent years, that in the central region has increased, while that in the western region has significantly declined. (2) A spatially linked network with a stable tourism environmental efficiency structure has been formed in China. The number of network relations and density of the network fluctuate and increase, while the network efficiency continues to decrease; however, a strong small-world nature is observed. (3) An obvious network core–edge structure is observed, with Shanghai, Beijing, Zhejiang, and Jiangsu at the center showing a significant intermediary role and remote provinces such as Tibet, Xinjiang, Ningxia, and Inner Mongolia at the edge showing fewer connections. (4) The four major plates of China based on the CONCOR algorithm are sparsely connected internally and show strong inter-plate connections and spillover effects. (5) The industry support capacity difference matrix, technological development level difference matrix, transportation accessibility difference matrix, and environmental regulation level difference matrix significantly and positively affect spatial associations, while the geographical distance matrix significantly and negatively affect spatial association relationship establishment. These findings have important theoretical and practical significance for the sustainable development of tourism in China's provinces and cities. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma could be treated by immunotherapy, which only has limited efficacy on uveal melanoma (UM). UM immunotyping for predicting immunotherapeutic responses and guiding immunotherapy should be better understood. This study identified molecular subtypes and key genetic markers associated with immunotherapy through immunosignature analysis. We screened a 6-immune cell signature simultaneously correlated with UM prognosis. Three immune subtypes (IS) were determined based on the 6-immune cell signature. Overall survival (OS) of IS3 was the longest. Significant differences of linear discriminant analysis (LDA) score were detected among the three IS types. IS3 with the highest LDA score showed a low immunosuppression. IS1 with the lowest LDA score was more immunosuppressive. LDA score was significantly negatively correlated with most immune checkpoint-related genes, and could reflect UM patients' response to anti-PD1 immunotherapy. Weighted correlation network analysis (WGCNA) identified that salmon, purple, yellow modules were related to IS and screened 6 prognostic genes. Patients with high-expressed NME1 and TMEM255A developed poor prognosis, while those with high-expressed BEX5 and ROPN1 had better prognosis. There was no notable difference in OS between patients with high-expressed LRRN1 and ST13 and those with low-expressed LRRN1 and ST13. NME1, TMEM255A, Bex5 and ROPN1 showed potential prognostic significance in UM. [ABSTRACT FROM AUTHOR]