Managing congestion at visitor hotspots using park-level use level data: Case study of a Chinese World Heritage Site.

Tourist congestion at hot spots has been a major management concern for UNESCO World Heritage Sites and other iconic protected areas. A growing number of heritage sites employ technologies, such as cameras and electronic ticket-checking systems, to monitor user levels, but data collected by these monitoring technologies are often under-utilized. In this study, we illustrated how to integrate data from hot spots by camera-captured monitoring and entrance counts to manage use levels at a World Heritage Site in Southeastern China. 6,930 photos of a congestion hotspot (scenic outlook on a trail) were collected within the park at a 10-minute interval over 105 days from January to November 2017. The entrance counts were used to predict daily average and maximum use level at the hotspots. Results showed that the average use level at the congestion hotspot did not exceed the use limit mandated by the park administration agency. However, from 9:20 am to 12:00 pm, the use level at hotspots exceeded visitor preferred use level. Visitor use level was significantly higher at the hotspot during a major Chinese "Golden Week". The daily entrance counts significantly predicted the average and maximum use level at the hotspot. Based on our findings, park managers can achieve the management goals by permitting the corresponding number of visitors passing the entrances. The gap manifested the complexities in visitor capacity management at high-use World Heritage Sites and other protected areas and calls for innovative monitoring and management strategies.

Knockout of CNR1 prevents metabolic stress-induced cardiac injury through improving insulin resistance (IR) injury and endoplasmic reticulum (ER) stress by promoting AMPK-alpha activation.

Obesity and diabetes are associated with diabetic cardiomyopathy (DCM). However, the pathogenesis of DCM is not fully understood. Cannabinoid receptor gene (CNR1) has been a drug target for the treatment of obesity. Here, we reported that CNR1 expression was increased in high fat diet (HFD)-induced heart of mice. Following, the wild type (CNR1+/+) and CNR1-knockout (CNR1-/-) mice were employed and subjected to HFD treatments for 16 weeks to further investigate the effects of CNR1 on DCM. The results indicated that CNR1 knockout mice after HFD feeding exhibited a significant decrease of body weight and lipid accumulation in serum. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) analysis indicated that HFD-induced insulin resistance was attenuated by CNR1 deficiency. HFD-triggered cardiac dysfunction was also improved by CNR1 knockout using echocardiographic analysis. Further, CNR1 suppression increased expressions of genes promoting fatty acid oxidation, and mitochondrial biogenesis. Also, TUNEL staining showed that CNR1 inhibition markedly reduced apoptotic levels in heart tissue sections of HFD-fed mice. Importantly, HFD-induced insulin resistance was prevented by CNR1-knockout through decreasing p-IRS1Ser expressions, and increasing phosphorylated insulin receptor substrate 1 (p-IRS1Tyr), phospho-AMP-activated protein kinase α (AMPKα) and phospho-acetyl-CoA carboxylase α (ACCα) expressions in heart tissue samples. In addition, CNR1 knockout impeded endoplasmic reticulum (ER) stress caused by HFD via down-regulating phospho-protein kinase-like ER kinase (PERK), phospho-eukaryotic initiation factor-2α (eIF2α), activating transcription factor 4 (ATF4) and ATF6 in heart tissue samples. Of note, we found that CNR1 knockout-improved insulin resistance, ER stress and lipid accumulation was diminished by AMPKα suppression using its inhibitor, Compound C. Therefore, the results demonstrated that therapeutic CNR1 inhibition could alleviate the progression of DCM.

Hypermethylation of DDAH2 promoter contributes to the dysfunction of endothelial progenitor cells in coronary artery disease patients.

BACKGROUND: Circulating endothelial progenitor cells (EPCs) may be a biomarker for vascular function and cardiovascular risk in patients with coronary artery disease (CAD). Dimethylarginine dimethylaminohydrolase 2 (DDAH2) regulates the function of EPCs. This study aimed to examine whether hypermethylation of DDAH2 promoter contributes to impaired function of EPCs in CAD patients. METHODS: Peripheral blood mono-nuclear cells from 25 CAD patients and 15 healthy volunteers were collected and differentiated into EPCs. EPCs were tested for their adhesive capability. DDAH2 mRNA expression was analyzed by real-time PCR, and the methylation of DDAH2 promoter was detected by bisulfite genomic sequencing. RESULTS: DDAH2 promoter in EPCs from CAD patients was hypermethylated and the methylation level was negatively correlated to DDAH2 mRNA level and adhesion function of EPCs. Homocysteine impaired the adhesion function of EPCs, accompanied by lower DDAH2 expression and higher methylation level of DDAH2 promoter, compared to controls. These effects of homocysteine were reversed by pretreatment with Aza, an inhibitor of DNA methyltransferase. CONCLUSION: Hypermethylation in DDAH2 promoter is positively correlated to the dysfunction of EPCs in CAD patients. Homocysteine disrupts EPCs function via inducing the hypermethylation of DDAH2 promoter, suggesting a key role of epigenetic mechanism in the progression of atherosclerosis.