MCP-1 levels in astrocyte-derived exosomes are changed in preclinical stage of Alzheimer's disease

BackgroundAlzheimer's disease (AD) is the most common form of dementia in older adults. There is accumulating evidence that inflammatory processes play a critical role in AD pathogenesis. In this study, we investigated whether inflammatory factors in plasma and astrocyte-derived exosomes (ADEs) from plasma are differentially expressed in the early stages of AD and their potential role in pathological processes in the AD continuum.MethodWe included 39 normal controls (NCs), 43 participants with subjective cognitive decline (SCD), and 43 participants with amnestic mild cognitive impairment (aMCI)/AD. IL-6, IL-8, and MCP-1 in plasma and ADEs from plasma were evaluated using a commercial multiplex Luminex-based kit.ResultsPairwise comparisons between the groups showed no significant differences in plasma levels of IL-6, IL-8, or MCP-1. However, ADEs in the SCD group showed an increase in MCP-1 levels compared to the NC group. To differentiate the preclinical group, discriminant analysis was performed using sex, age, years of education, and genotype. This revealed a difference between the SCD and NC groups (area under the curve: 0.664). A Spearman correlation analysis of MCP-1 in plasma and ADEs showed no or weak correlation in the SCD (R = 0.150, p = 0.350) and aMCI/AD (R = 0.310, p = 0.041) groups, while a positive correlation in the NC group (R = 0.360, p = 0.026).ConclusionPlasma IL-6, IL-8, and MCP-1 levels were not significantly different. However, the concentration of MCP-1 in ADEs is slightly altered during the preclinical phase of AD, which could be a potential role of the central neuron system (CNS) immune response in the AD continuum.Clinical trial registrationwww.ClinicalTrials.gov, identifier: NCT03370744

Spatial and temporal changes in the coupling of ecological environment and tourism development: the case of Kyushu, Japan

The relationship between the ecological environment and tourism development is extremely complex. Summarizing evolutionary trends, temporal patterns and spatial differences in time and space can contribute to the coordinated development of an ecological environment and tourism. Based on the Carrying capacity–Supporting capability–Attraction capability–Evolutional capability–Development capability model and the Pressure–State–Response model, this paper proposes a conceptual index system using the entropy weight method and the coupled coordination degree model. The coupling coordination relationship between the ecological environment and tourism development in seven prefectures in the Kyushu region of Japan from 2010 to 2019 was analyzed. Then, using the membership degree model, the coordinated development of each prefecture was further analyzed. The results mainly show that in the Kyushu region, the degree of coupling coordination between the ecological environment and the tourism development system changed from moderate coordination to marginal coordination during the study period, then steadily improved, with large differences between regions. Based on the analysis results, this paper puts forward specific suggestions for the prefectures with lagging tourism development and lagging ecological environment development, respectively, to provide a reference path for the sustainable development of the ecological environment and tourism in the Kyushu region. For prefectures in the ecological environment development lag-type stage, the following requirements were identified: (a) the need for the government to strengthen tourism infrastructures; (b) the need for the government to focus on developing regional ecotourism, focusing on the fragility of island ecosystems and the sustainability of resources in the Kyushu region; (c) the need for the government to scientifically formulate tourism-related policies and plan tourism-related investments. For prefectures in the tourism development lag-type stage, the following were identified: (a) the need for the government to develop a variety of tourism products and create regional tourism brands based on local conditions; (b) prefectures should determine the main tourism functions and themes it offers based on the specifics of their resource advantages

Ganoderma lucidum Protects Dopaminergic Neuron Degeneration through Inhibition of Microglial Activation

Abundant evidence has suggested that neuroinflammation participates in the pathogenesis of Parkinson's disease (PD). The emerging evidence has supported that microglia may play key roles in the progressive neurodegeneration in PD and might be a promising therapeutic target. Ganoderma lucidum (GL), a traditional Chinese medicinal herb, has been shown potential neuroprotective effects in our clinical trials that make us to speculate that it might possess potent anti-inflammatory and immunomodulating properties. To test this hypothesis, we investigated the potential neuroprotective effect of GL and possible underlying mechanism of action through protecting microglial activation using co-cultures of dopaminergic neurons and microglia. The microglia is activated by LPS and MPP+-treated MES 23.5 cell membranes. Meanwhile, GL extracts significantly prevent the production of microglia-derived proinflammatory and cytotoxic factors [nitric oxide, tumor necrosis factor-α (TNF-α), interlukin 1β (IL-1β)] in a dose-dependent manner and down-regulate the TNF-α and IL-1β expressions on mRNA level as well. In conclusion, our results support that GL may be a promising agent for the treatment of PD through anti-inflammation

Genomic heterogeneity of multiple synchronous lung cancer

Multiple synchronous lung cancers (MSLCs) present a clinical dilemma as to whether individual tumours represent intrapulmonary metastases or independent tumours. In this study we analyse genomic profiles of 15 lung adenocarcinomas and one regional lymph node metastasis from 6 patients with MSLC. All 15 lung tumours demonstrate distinct genomic profiles, suggesting all are independent primary tumours, which are consistent with comprehensive histopathological assessment in 5 of the 6 patients. Lung tumours of the same individuals are no more similar to each other than are lung adenocarcinomas of different patients from TCGA cohort matched for tumour size and smoking status. Several known cancer-associated genes have different mutations in different tumours from the same patients. These findings suggest that in the context of identical constitutional genetic background and environmental exposure, different lung cancers in the same individual may have distinct genomic profiles and can be driven by distinct molecular events

Metabonomics research accelerates discovery of medical biomarkers

Biomarker refers to a characteristic that can be objectively detected and evaluated, and can be used as an indicator of normal biological process, pathological process or therapeutic intervention pharmacological response. As one of the key words of individualized medicine, the search and discovery of valuable biomarkers has become a research hotspot in the current medical field

Spatial and temporal changes in the coupling of ecological environment and tourism development: the case of Kyushu, Japan

The relationship between the ecological environment and tourism development is extremely complex. Summarizing evolutionary trends, temporal patterns and spatial differences in time and space can contribute to the coordinated development of an ecological environment and tourism. Based on the Carrying capacity–Supporting capability–Attraction capability–Evolutional capability–Development capability model and the Pressure–State–Response model, this paper proposes a conceptual index system using the entropy weight method and the coupled coordination degree model. The coupling coordination relationship between the ecological environment and tourism development in seven prefectures in the Kyushu region of Japan from 2010 to 2019 was analyzed. Then, using the membership degree model, the coordinated development of each prefecture was further analyzed. The results mainly show that in the Kyushu region, the degree of coupling coordination between the ecological environment and the tourism development system changed from moderate coordination to marginal coordination during the study period, then steadily improved, with large differences between regions. Based on the analysis results, this paper puts forward specific suggestions for the prefectures with lagging tourism development and lagging ecological environment development, respectively, to provide a reference path for the sustainable development of the ecological environment and tourism in the Kyushu region. For prefectures in the ecological environment development lag-type stage, the following requirements were identified: (a) the need for the government to strengthen tourism infrastructures; (b) the need for the government to focus on developing regional ecotourism, focusing on the fragility of island ecosystems and the sustainability of resources in the Kyushu region; (c) the need for the government to scientifically formulate tourism-related policies and plan tourism-related investments. For prefectures in the tourism development lag-type stage, the following were identified: (a) the need for the government to develop a variety of tourism products and create regional tourism brands based on local conditions; (b) prefectures should determine the main tourism functions and themes it offers based on the specifics of their resource advantages

Announcement effects of mergers and acquisitions on financial institutions in Asia Pacific

This study seeks to address the announcement effect of Merger and Acquisitions (M&A) of the financial institutions in Asia Pacific. The research involves 92 successful merger transactions which took place between 1995 and 2010. Based on the efficient market hypothesis, share prices reflect the information for publicly listed firms. In this paper, an event study was conducted to measure the changes in shareholders’ value of the acquiring and target companies. In addition, a regression is employed to identify the influences to abnormal returns brought about by M&A. Our results showed that target firms, on average, gained shareholder value in different window periods. Bidder firms, on the other hand, revealed varying results that are predominantly gains but also include both zero and minimal losses.BUSINES

Robust Automatic Target Recognition Algorithm for Large-Scene SAR Images and Its Adaptability Analysis on Speckle

Aiming at the multiple target recognition problems in large-scene SAR image with strong speckle, a robust full-process method from target detection, feature extraction to target recognition is studied in this paper. By introducing a simple 8-neighborhood orthogonal basis, a local multiscale decomposition method from the center of gravity of the target is presented. Using this method, an image can be processed with a multilevel sampling filter and the target’s multiscale features in eight directions and one low frequency filtering feature can be derived directly by the key pixels sampling. At the same time, a recognition algorithm organically integrating the local multiscale features and the multiscale wavelet kernel classifier is studied, which realizes the quick classification with robustness and high accuracy for multiclass image targets. The results of classification and adaptability analysis on speckle show that the robust algorithm is effective not only for the MSTAR (Moving and Stationary Target Automatic Recognition) target chips but also for the automatic target recognition of multiclass/multitarget in large-scene SAR image with strong speckle; meanwhile, the method has good robustness to target’s rotation and scale transformation

Temporal Stability of Vegetation Cover across the Loess Plateau Based on GIMMS during 1982–2013

The Loess Plateau, covering approximately 640,000 km2, has experienced the most severe soil erosion in the world. A greening tendency has been noticed since implementing the Grain to Green Program (GTGP), which may prevent further soil erosion. Therefore, understanding the underpinning basis of greening stability and persistence is important for sustainable improvement. Global Inventory Modeling and Mapping Studies (GIMMS) normalized difference vegetation index (NDVI) datasets for 1982–2013 were used to investigate the temporal stability and persistent time (PT) of vegetation over the Loess Plateau, utilizing the coefficient of variation (CV) and the estimation of tendencies of vegetation greening starting from the selected reference conditions. Two periods from 1982 to 1999 (as the reference period) and 2000 to 2013 were selected by considering the GTGP since 1999. The results indicate that: (1) A significant increase in vegetation cover occurred in the low NDVI area (NDVI < 0.3), with a high fluctuation from 2000 to 2013 compared with the reference period. Moreover, the fluctuation in vegetation is more related to precipitation variation since 1999. (2) Most areas recovered in the greening trend of the first period starting in 2009, occurring in 28.7% (2628 of 9148) of the total area. (3) The revegetated areas have a low PT and a high CVvi, that is, the revegetated areas need a long time to recover from disturbances. Therefore, we identify the sensitive areas with PT = 4; further management needs to be implemented for sustainable development in these areas. These results provide a method to quantify the stability and persistence of the complex interactions between vegetation greenness and environmental changes, particularly in fragile areas