Tauroursodeoxycholic acid: a bile acid that may be used for the prevention and treatment of Alzheimer’s disease

Alzheimer’s disease (AD) is a prevalent neurodegenerative disease that has become one of the main factors affecting human health. It has serious impacts on individuals, families, and society. With the development of population aging, the incidence of AD will further increase worldwide. Emerging evidence suggests that many physiological metabolic processes, such as lipid metabolism, are implicated in the pathogenesis of AD. Bile acids, as the main undertakers of lipid metabolism, play an important role in the occurrence and development of Alzheimer’s disease. Tauroursodeoxycholic acid, an endogenous bile acid, has been proven to possess therapeutic effects in different neurodegenerative diseases, including Alzheimer’s disease. This review tries to find the relationship between bile acid metabolism and AD, as well as explore the therapeutic potential of bile acid taurocursodeoxycholic acid for this disease. The potential mechanisms of taurocursodeoxycholic acid may include reducing the deposition of Amyloid-β protein, regulating apoptotic pathways, preventing tau hyperphosphorylation and aggregation, protecting neuronal synapses, exhibiting anti-inflammatory properties, and improving metabolic disorders. The objective of this study is to shed light on the use of tauroursodeoxycholic acid preparations in the prevention and treatment of AD, with the aim of identifying effective treatment targets and clarifying various treatment mechanisms involved in this disease

Randomized controlled trial of a coordinated care intervention to improve risk factor control after stroke or transient ischemic attack in the safety net: Secondary stroke prevention by Uniting Community and Chronic care model teams Early to End Disparities (SUCCEED).

BackgroundRecurrent strokes are preventable through awareness and control of risk factors such as hypertension, and through lifestyle changes such as healthier diets, greater physical activity, and smoking cessation. However, vascular risk factor control is frequently poor among stroke survivors, particularly among socio-economically disadvantaged blacks, Latinos and other people of color. The Chronic Care Model (CCM) is an effective framework for multi-component interventions aimed at improving care processes and outcomes for individuals with chronic disease. In addition, community health workers (CHWs) have played an integral role in reducing health disparities; however, their effectiveness in reducing vascular risk among stroke survivors remains unknown. Our objectives are to develop, test, and assess the economic value of a CCM-based intervention using an Advanced Practice Clinician (APC)-CHW team to improve risk factor control after stroke in an under-resourced, racially/ethnically diverse population.Methods/designIn this single-blind randomized controlled trial, 516 adults (≥40 years) with an ischemic stroke, transient ischemic attack or intracerebral hemorrhage within the prior 90 days are being enrolled at five sites within the Los Angeles County safety-net setting and randomized 1:1 to intervention vs usual care. Participants are excluded if they do not speak English, Spanish, Cantonese, Mandarin, or Korean or if they are unable to consent. The intervention includes a minimum of three clinic visits in the healthcare setting, three home visits, and Chronic Disease Self-Management Program group workshops in community venues. The primary outcome is blood pressure (BP) control (systolic BP <130 mmHg) at 1 year. Secondary outcomes include: (1) mean change in systolic BP; (2) control of other vascular risk factors including lipids and hemoglobin A1c, (3) inflammation (C reactive protein [CRP]), (4) medication adherence, (5) lifestyle factors (smoking, diet, and physical activity), (6) estimated relative reduction in risk for recurrent stroke or myocardial infarction (MI), and (7) cost-effectiveness of the intervention versus usual care.DiscussionIf this multi-component interdisciplinary intervention is shown to be effective in improving risk factor control after stroke, it may serve as a model that can be used internationally to reduce race/ethnic and socioeconomic disparities in stroke in resource-constrained settings.Trial registrationClinicalTrials.gov Identifier NCT01763203

Randomized controlled trial of a coordinated care intervention to improve risk factor control after stroke or transient ischemic attack in the safety net: Secondary stroke prevention by Uniting Community and Chronic care model teams Early to End Disparities (SUCCEED)

BACKGROUND: Recurrent strokes are preventable through awareness and control of risk factors such as hypertension, and through lifestyle changes such as healthier diets, greater physical activity, and smoking cessation. However, vascular risk factor control is frequently poor among stroke survivors, particularly among socio-economically disadvantaged blacks, Latinos and other people of color. The Chronic Care Model (CCM) is an effective framework for multi-component interventions aimed at improving care processes and outcomes for individuals with chronic disease. In addition, community health workers (CHWs) have played an integral role in reducing health disparities; however, their effectiveness in reducing vascular risk among stroke survivors remains unknown. Our objectives are to develop, test, and assess the economic value of a CCM-based intervention using an Advanced Practice Clinician (APC)-CHW team to improve risk factor control after stroke in an under-resourced, racially/ethnically diverse population. METHODS/DESIGN: In this single-blind randomized controlled trial, 516 adults (≥40 years) with an ischemic stroke, transient ischemic attack or intracerebral hemorrhage within the prior 90 days are being enrolled at five sites within the Los Angeles County safety-net setting and randomized 1:1 to intervention vs usual care. Participants are excluded if they do not speak English, Spanish, Cantonese, Mandarin, or Korean or if they are unable to consent. The intervention includes a minimum of three clinic visits in the healthcare setting, three home visits, and Chronic Disease Self-Management Program group workshops in community venues. The primary outcome is blood pressure (BP) control (systolic BP <130 mmHg) at 1 year. Secondary outcomes include: (1) mean change in systolic BP; (2) control of other vascular risk factors including lipids and hemoglobin A1c, (3) inflammation (C reactive protein [CRP]), (4) medication adherence, (5) lifestyle factors (smoking, diet, and physical activity), (6) estimated relative reduction in risk for recurrent stroke or myocardial infarction (MI), and (7) cost-effectiveness of the intervention versus usual care. DISCUSSION: If this multi-component interdisciplinary intervention is shown to be effective in improving risk factor control after stroke, it may serve as a model that can be used internationally to reduce race/ethnic and socioeconomic disparities in stroke in resource-constrained settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01763203

Study on Photon Dose of Ultra-intense and Ultra-short Laser Facility Based on Fully Monte-Carlo Simulation

The possibility of using lasers to achieve previously unobtainable states of matter in the laboratory gained much attention following the demonstration of the first pulsed laser in 1960. In the following few years there was plenty research activity as attempts were made to increase the peak power and focused intensity in order to reach extreme conditions within the laboratory. Laser-acceleration technology is rapidly developing. Petawatt class lasers have been constructed for specific research activities, including particle acceleration, inertial confinement fusion and radiation therapy, and for secondary source generation (X rays, electrons, protons, neutrons and ions). As a new source of ionizing radiation, dose measurement in ultra-intense and ultra-short laser facilities is of great value for radiation protection of the environment, occupational staff and shielding design in laser device design stage. Owing to the pulsed and mixed characteristics of radiation field around the laser facility, it is really challenging to accurately measure the dose equivalent induced by bremsstrahlung photon in the target chamber of the laser facility. Moreover, the rationality of dose assessment model needs more experimental data and to be further verified. To reach this point, the Monte-Carlo program FLUKA was employed to characterize the radiation filed distribution. Firstly, a complete and thorough target chamber module was established according to the XG-Ⅲ geometry parameter and material composition. The in-chamber and out-chamber dose distribution were then calculated and analyzed based on the existing theoretical model of electron source term and typical experimental conditions. The electron energy distribution, characteristic electron temperature, scaling laws and laser-to-energy conversion efficiency were introduced. Secondly, the typical electron spectrum was divided into four intervals. The portion of different energy intervals to the total equivalent dose was determined. Thirdly, a bremsstrahlung photon dose equivalent measuring module was designed and optimized for ultra-intense and ultra-short laser facilities. The simulation results indicate that: 1) The electron dose equivalent is higher than the bremsstrahlung photons both inside and outside the target chamber; 2) The dose equivalent contribution of 0.15 MeV electron energy interval to the total energy range is dominant, and the module was design based on the conclusion; 3) The designed module mainly consists of PMMA and metallic shielding material. With this approach, the module can reduce the electron dose equivalent to 0.3% and photon dose equivalent to 69.1%. The dose ratio of electron to photon is about 128%. In addition, 5% of the total photon dose is contributed by the occurrence of bremsstrahlung of highenergy electron in PMMA

Biodiversity arks in the Anthropocene

The Anthropocene proposal suggested that the Earth may have entered a new geological epoch, in which human activity and climate change are influencing the environment at global scale. Arrival of the Anthropocene is bringing an unprecedented challenge to the biodiversity that is essential to humans, and enhancing many benefits of nature to human being. However, biodiversity loss is aggravating in the rhythm of inevitable change in the Anthropocene, and the adaptation of biodiversity to the anthropogenic disturbance seems unable to keep pace with the human activity and climate change. Therefore, re-examination of the assumptions and practices upon the current conservation endeavor are needed. We suggested that biodiversity conservation should be paid more attention to the response from biodiversity to the human activity and climate change in the Anthropocene. Thus, the concept of biodiversity arks in the Anthropocene is proposed, that is, biodiversity arks in the Anthropocene are the areas where vulnerable biodiversity is sheltered to alleviate human activity and buffered from climate change under the anthropogenic disturbance. The concept should be implemented for biodiversity conservation to fill gaps between our knowledge and build on successful conservation and sustainability in the Anthropocene. It will be certainly important to conservation policy instruction and management under climate change, especially the implementation of climate buffering zones preserving biodiversity in the face of warming climate

Degradation Characteristics and Remediation Ability of Contaminated Soils by Using &beta;-HCH Degrading Bacteria

Three degradation strains that can utilize &beta;-Hexachlorocyclohexanes (&beta;-HCH) as the sole carbon source were isolated from the soil substrate of constructed wetland under long-term &beta;-HCH stress, and they were named A1, J1, and M1. Strains A1 and M1 were identified as Ochrobactrum sp. and strain J1 was identified as Microbacterium oxydans sp. by 16S rRNA gene sequence analysis. The optimum conditions for degradation with these three strains, A1, J1, and M1, were pH = 7, 30 &deg;C, and 5% inoculum amount, and the degradation rates of 50 &mu;g/L &beta;-HCH under these conditions were 58.33%, 51.96%, and 50.28%, respectively. Degradation characteristics experiments showed that root exudates could increase the degradation effects of A1 and M1 on &beta;-HCH by 6.95% and 5.82%, respectively. In addition, the degradation bacteria A1 and J1 mixed in a ratio of 1:1 had the highest degradation rate of &beta;-HCH, which was 69.57%. An experiment on simulated soil remediation showed that the compound bacteria AJ had the best effect on promoting the degradation of &beta;-HCH in soil within 98 d, and the degradation rate of &beta;-HCH in soil without root exudates was 60.22%, whereas it reached 75.02% in the presence of root exudates. The addition of degradation bacteria or degradation bacteria-root exudates during soil remediation led to dramatic changes in the community structure of the soil microorganisms, as well as a significant increase in the proportion of aerobic and Gram-negative bacterial groups. This study can enrich the resources of &beta;-HCH degrading strains and provided a theoretical basis for the on-site engineering treatment of &beta;-HCH contamination

Degradation Characteristics and Remediation Ability of Contaminated Soils by Using <i>β</i>-HCH Degrading Bacteria

Three degradation strains that can utilize β-Hexachlorocyclohexanes (β-HCH) as the sole carbon source were isolated from the soil substrate of constructed wetland under long-term β-HCH stress, and they were named A1, J1, and M1. Strains A1 and M1 were identified as Ochrobactrum sp. and strain J1 was identified as Microbacterium oxydans sp. by 16S rRNA gene sequence analysis. The optimum conditions for degradation with these three strains, A1, J1, and M1, were pH = 7, 30 °C, and 5% inoculum amount, and the degradation rates of 50 μg/L β-HCH under these conditions were 58.33%, 51.96%, and 50.28%, respectively. Degradation characteristics experiments showed that root exudates could increase the degradation effects of A1 and M1 on β-HCH by 6.95% and 5.82%, respectively. In addition, the degradation bacteria A1 and J1 mixed in a ratio of 1:1 had the highest degradation rate of β-HCH, which was 69.57%. An experiment on simulated soil remediation showed that the compound bacteria AJ had the best effect on promoting the degradation of β-HCH in soil within 98 d, and the degradation rate of β-HCH in soil without root exudates was 60.22%, whereas it reached 75.02% in the presence of root exudates. The addition of degradation bacteria or degradation bacteria-root exudates during soil remediation led to dramatic changes in the community structure of the soil microorganisms, as well as a significant increase in the proportion of aerobic and Gram-negative bacterial groups. This study can enrich the resources of β-HCH degrading strains and provided a theoretical basis for the on-site engineering treatment of β-HCH contamination

Purification Effects on β-HCH Removal and Bacterial Community Differences of Vertical-Flow Constructed Wetlands with Different Vegetation Plantations

This study aimed to investigate the removal of β-hexachlorocyclohexane (β-HCH) at realistic concentration levels (10 µg/L) in different plant species in constructed wetlands (Acorus calamus, Canna indica, Thalia dealbata, and Pontederia cordata) and the structure of the rhizosphere microbial community response of each group during summer and winter. Results showed that all groups of constructed wetlands had very good decontamination efficiency against β-HCH in water (90.86–98.17%). The species that most efficiently purified β-HCH in water was A. calamus in summer (98.17%) and C. indica in winter (96.64%). Substrate sorption was found to be the major pathway for β-HCH removal from water in the constructed wetlands. The ability of the wetland plants to absorb and purify β-HCH was limited, and C. indica had the strongest absorptive capacity among the four plant species. The mean β-HCH removal from the matrix of the planted plants increased by 5.8% compared with that of the control treatment (unplanted plants). The average β-HCH content in the plant rhizosphere substrate was 4.15 µg/kg lower than that in the non-rhizosphere substrate. High-throughput sequencing analysis revealed significant differences (P Actinobacteria and Sphingomonas remarkably increased over time in summer

Socioeconomic and Environmental Impacts on Regional Tourism across Chinese Cities: A Spatiotemporal Heterogeneous Perspective

Understanding geospatial impacts of multi-sourced drivers on the tourism industry is of great significance for formulating tourism development policies tailored to regional-specific needs. To date, no research in China has explored the combined impacts of socioeconomic and environmental drivers on city-level tourism from a spatiotemporal heterogeneous perspective. We collected the total tourism revenue indicator and 30 potential influencing factors from 343 cities across China during 2008–2017. Three mainstream regressions and an emerging local spatiotemporal regression named the Bayesian spatiotemporally varying coefficients (Bayesian STVC) model were constructed to investigate the global-scale stationary and local-scale spatiotemporal nonstationary relationships between city-level tourism and various vital drivers. The Bayesian STVC model achieved the best model performance. Globally, eight socioeconomic and environmental factors, average wage (coefficient: 0.47, 95% credible intervals: 0.43–0.51), employed population (−0.14, −0.17–−0.11), GDP per capita (0.47, 0.42–0.52), population density (0.21, 0.16–0.27), night-time light index (−0.01, −0.08–0.05), slope (0.10, 0.06–0.14), vegetation index (0.66, 0.63–0.70), and road network density (0.34, 0.29–0.38), were identified to have nonlinear effects on tourism. Temporally, the main drivers might have gradually changed from the local macro-economic level, population density, and natural environment conditions to the individual economic level over the last decade. Spatially, city-specific dynamic maps of tourism development and geographically clustered influencing maps for eight drivers were produced. In 2017, China formed four significant city-level tourism industry clusters (hot spots, 90% confidence), the locations of which coincide with China’s top four urban agglomerations. Our local spatiotemporal analysis framework for geographical tourism data is expected to provide insights into adjusting regional measures to local conditions and temporal variations in broader social and natural sciences

Interaction between rpsL and gyrA mutations affects the fitness and dual resistance of Mycobacterium tuberculosis clinical isolates against streptomycin and fluoroquinolones

Background: The interaction between different drug-resistant mutations is important to the development of drug resistance and its evolution. In this study, we aimed to reveal the potential relationships between mutations conferring resistance to two important antituberculosis drugs streptomycin (STR) and fluoroquinolones (FLQ). Materials and methods We used an in vitro competitive fitness assay to reveal the interactions between different mutations of rpsL and gyrA in drug-resistant Mycobacterium smegmatis, followed by the analysis of the frequency of rpsL and gyrA mutation combinations in 213 STR–FLQ dual-resistant clinical Mycobacterium tuberculosis isolates from Sichuan region, which was also investigated by the whole genome data from 3,056 global clinical M. tuberculosis isolates. Results: The strains with K43R and K88R mutation in rpsL showed no difference in relative fitness compared with their susceptible ancestor, while K43N, K43M, K43T, and K88E exhibited a significantly lower relative fitness (P<0.05). For the FLQ-resistant mutants, all mutation types showed no difference in their relative fitness. Among STR–FLQ dual-resistant M. smegmatis strains, a lower fitness was detected in those with K43N/M/T and K88E instead of K43R and K88R mutations in rpsL. Among M. tuberculosis isolates harboring rpsL and gyrA dual mutations, the most two frequent combinatorial mutation types were K43R/D94G (n=37) and K43R/A90V (n=24), with the former being the most frequent one by both in vitro tests and clinical survey. Conclusion: Our results suggest that the interaction between rpsL and gyrA mutations affects the fitness cost in STR–FLQ dual-resistant M. smegmatis and also the predilection of mutation combinations in clinical M. tuberculosis isolates