Inhibition of Aldose Reductase Activates Hepatic Peroxisome Proliferator-Activated Receptor-α and Ameliorates Hepatosteatosis in Diabetic db/db Mice

We previously demonstrated in streptozotocin-induced diabetic mice that deficiency or inhibition of aldose reductase (AR) caused significant dephosphorylation of hepatic transcriptional factor PPARα, leading to its activation and significant reductions in serum lipid levels. Herein, we report that inhibition of AR by zopolrestat or by a short-hairpin RNA (shRNA) against AR caused a significant reduction in serum and hepatic triglycerides levels in 10-week old diabetic db/db mice. Meanwhile, hyperglycemia-induced phosphorylation of hepatic ERK1/2 and PPARα was significantly attenuated in db/db mice treated with zopolrestat or AR shRNA. Further, in comparison with the untreated db/db mice, the hepatic mRNA expression of Aco and ApoA5, two target genes for PPARα, was increased by 93% (P < 0.05) and 73% (P < 0.05) in zopolrestat-treated mice, respectively. Together, these data indicate that inhibition of AR might lead to significant amelioration in hyperglycemia-induced dyslipidemia and nonalcoholic fatty liver disease

Association of PCSK1 rs6234 with Obesity and Related Traits in a Chinese Han Population

Background: Common variants in PCSK1 have been reported to be associated with obesity in populations of European origin. We aimed to replicate this association in Chinese. Methodology/Principal Findings: Two PCSK1 variants rs6234 and rs6235 (in strong LD with each other, r 2 = 0.98) were genotyped in a population-based cohort of 3,210 Chinese Hans. The rs6234 was used for further association analyses with obesity and related traits. We found no significant association of rs6234 with obesity, overweight, BMI, waist circumference, or body fat percentage (P.0.05) in all participants. However, the rs6234 G-allele showed a significant association with increased risk of combined phenotype of obesity and overweight (OR 1.21[1.03–1.43], P = 0.0193) and a trend toward association with obesity (OR 1.25[0.98–1.61], P = 0.08) in men, but not in women (P$0.29). Consistently, the rs6234 G-allele showed significant association with increased BMI (P = 0.0043), waist circumference (P = 0.008) and body fat percentage (P = 0.0131) only in men, not in women (P$0.24). Interestingly, the rs6234 G-allele was significantly associated with increased HOMA-B (P = 0.0059) and decreased HOMA-S (P = 0.0349) in all participants. Conclusion/Significance: In this study, we found modest evidence for association of the PCSK1 rs6234 with BMI and overweight in men only but not in women, which suggested that PCSK1 rs6234 might not be an important contributor t

Effects of Body Fat on the Associations of High-Molecular-Weight Adiponectin, Leptin and Soluble Leptin Receptor with Metabolic Syndrome in Chinese

BACKGROUND: Little is known regarding the associations between high-molecular-weight (HMW-) adiponectin, leptin and soluble leptin receptor (sOB-R) and metabolic syndrome (MetS) in Chinese. Also few studies elucidate the effects of inflammation and body fat mass on the relations. METHODS: Plasma HMW-adiponectin, leptin and sOB-R were measured among 1055 Chinese men and women (35∼54 yrs). Whole body and trunk fat mass were determined by Dual-energy X-ray absorptiometry. MetS was defined by the updated NCEP/ATPIII criterion for Asian-Americans. RESULTS: HMW-adiponectin was inversely associated with MetS in multivariate model including fat mass index (FMI), inflammatory markers, leptin and sOB-R (OR in the highest quartile= 0.30, 95%CI 0.18∼0.50, P<.0001). Plasma sOB-R was also inversely associated with MetS independent of body fatness and inflammatory markers, whereas the association was somewhat attenuated after adjusting HMW-adiponectin (OR for the highest quartile = 0.78, 95%CI 0.47∼1.32, P = 0.15). In contrast, leptin was associated with increased odds of MetS independent of inflammatory markers, HMW-adiponectin, and sOB-R (OR for the highest quartile= 2.64, 95%CI 1.35∼5.18, P = 0.006), although further adjustment for FMI abolished this association. CONCLUSIONS: HMW-adiponectin exhibited strong inverse associations with MetS independent of body composition, inflammation, leptin and sOB-R; while the associations of leptin and sOB-R were largely explained by fat mass or HMW-adiponectin, respectively

Body Mass Index and Diabetes in Asia: A Cross-Sectional Pooled Analysis of 900,000 Individuals in the Asia Cohort Consortium

10.1371/journal.pone.0019930PLoS ONE66

Diabetes and the Risk of Multi-System Aging Phenotypes: A Systematic Review and Meta-Analysis

[[abstract]]Background: Observational studies suggested an association between diabetes and the risk of various geriatric conditions (i.e., cognitive impairment, dementia, depression, mobility impairment, disability, falls, and urinary incontinence). However, the magnitude and impact of diabetes on older adults have not been reviewed. Methodology/Principal Findings: MEDLINE and PSYCINFO databases were searched through November 2007 for published studies, supplemented by manual searches of bibliographies of key articles. Population-based, prospective cohort studies that reported risk of geriatric outcomes in relation to diabetes status at baseline were selected. Two authors independently extracted the data, including study population and follow-up duration, ascertainment of diabetes status at baseline, outcomes of interest and their ascertainment, adjusted covariates, measures of association, and brief results. Fifteen studies examined the association of DM with cognitive dysfunction. DM was associated with a faster decline in cognitive function among older adults. The pooled adjusted risk ratio (RR) for all dementia when persons with DM were compared to those without was 1.47 (95% CI, 1.25 to 1.73). Summary RRs for Alzheimer's disease and vascular dementia comparing persons with DM to those without were 1.39 (CI, 1.16 to 1.66) and 2.38 (CI, 1.79 to 3.18), respectively. Four of 5 studies found significant association of DM with faster mobility decline and incident disability. Two studies examined the association of diabetes with falls in older women. Both found statistically significant associations. Insulin users had higher RR for recurrent falls. One study for urinary incontinence in older women found statistically significant associations. Two studies for depression did not suggest that DM was an independent predictor of incident depression. Conclusions/Significance: Current evidence supports that DM is associated with increased risk for selected geriatric conditions. Clinicians should increase their awareness and provide appropriate care. Future research is required to elucidate the underlying pathological pathway. 2009 Lu et al

Characteristics of Heavy Storms and the Scaling Relation with Air Temperature by Event Process-Based Analysis in South China

The negative scaling rate between precipitation extremes and the air temperature in tropic and subtropic regions is still a puzzling issue. This study investigates the scaling rate from two aspects, storm characteristics (types) and event process-based temperature variations. Heavy storms in South China are developed by different weather systems with unique meteorological characteristics each season, such as the warm-front storms (January), cold-front storms (April to mid-May), monsoon storms (late May to June), convective storms, and typhoon storms (July to September). This study analyzes the storm characteristics using the hourly rainfall data from 1990 to 2017; compares the storm hyetographs derived from the one-minute rainfall data during 2008–2017; and investigates the interactions between heavy storms and meteorological factors including air temperature, relative humidity, surface pressure, and wind speed at 42 weather stations in Guangzhou during 2015–2017. Most storms, except for typhoon and warm-front storms, had a short duration (3 h) and intense rates (~13 mm/h) in Guangzhou, South China. Convective storms were dominant (50%) in occurrence and had the strongest intensity (15.8 mm/h). Storms in urban areas had stronger interactions with meteorological factors and showed different hyetographs from suburban areas. Meteorological factors had larger variations with the storms that occurred in the day time than at night. The air temperature could rise 6 °C and drop 4 °C prior to and post-summer storms against the diurnal mean state. The 24-hour mean air temperature prior to the storms produced more reliable scaling rates than the naturally daily mean air temperature. The precipitation extremes showed a peak-like scaling relation with the 24-hour mean air temperature and had a break temperature of 28 °C. Below 28 °C, the relative humidity was 80%–100%, and it showed a positive scaling rate. Above 28 °C, the negative scaling relation was likely caused by a lack of moisture in the atmosphere, where the relative humidity decreased with the air temperature increase

Willingness and uptake of the COVID-19 testing and vaccination in urban China during the low-risk period : a cross-sectional study

Background: Regular testing and vaccination are effective measures to mitigate the ongoing COVID-19 pandemic. Evidence on the willingness and uptake of the COVID-19 testing is scarce, and the willingness and uptake of vaccination may change as the pandemic evolves. This study aims to examine willingness and uptake of COVID-19 testing and vaccination during a low-risk period of the COVID-19 pandemic in urban China. Methods: A cross-sectional online survey was conducted among 2244 adults in urban China. Descriptive analyses were performed to compare the respondents’ willingness and uptake of COVID-19 testing and vaccination. Multivariate logistic regressions were fitted to investigate factors associated with the willingness and uptake of the two measures. Results: In early 2021, about half (52.45%) of the respondents had received or scheduled a COVID-19 test at least once, and a majority (95.63%) of the respondents were willing to receive testing. About two-thirds (63.28%) of the respondents had received/scheduled or were willing to receive a COVID-19 vaccine. Willingness and uptake of COVID-19 testing were not associated with socio-demographic characteristics, except for occupation. Being of older age, migrants, having higher educational attainment and secure employment were associated with a higher uptake of COVID-19 vaccination among the surveyed respondents, while willingness to vaccinate was consistent across socio-demographic characteristics among those who had not been vaccinated. Conclusions: By early 2021, Chinese adults expressed almost universal willingness of COVID-19 testing and over half of adults have been tested, while the willingness and uptake of COVID-19 vaccination were relatively low at the low-risk period of the COVID-19 pandemic. Maintaining willingness of COVID-19 vaccination is critical and necessary, especially when the pandemic evolved into a low-risk period.publishedVersionPeer reviewe

The Role of NADPH Oxidase in Multi-Walled Carbon Nanotubes-Induced Oxidative Stress and Cytotoxicity in Human Macrophages

Natural Science Foundation of China [30901175]; Science and Technology Innovation Project of Fujian Province for Young Scientific Researchers, China [2008F3097]Recent studies suggest reactive oxygen species (ROS) induced in mammalian cells exposed to multi-walled carbon nanotubes (MWCNTs) could mediate the cytotoxicity. This study was conducted to determine the mechanisms responsible for MWCNTs-induced ROS production in human primary macrophages. Our results showed that superoxide levels were significantly increased in a time-dependent manner in blood monocyte-derived macrophages treated with 100 mu g/ml MWCNTs for 12 h. Concomitantly, MWCNTs induced membrane translocation of the NADPH oxidase subunits p47(phox) and p67(phox), a signature event for NADPH oxidase activation. Pre-incubation with apocynin, a selective inhibitor of NADPH oxidase, prevented both membrane translocation of p47(phox) and superoxide production. Treatment with MWCNTs also resulted in an increased cytotoxicity in human primary macrophages that was significantly attenuated by both apocynin and antioxidants. These findings demonstrate that MWCNTs activate NADPH oxidase in human macrophages, which may contribute to ROS generation in MWCNTs treated-macrophages

Performance Evaluation of Real-Time Precise Point Positioning with Both BDS-3 and BDS-2 Observations

For time-critical precise applications, one popular technology is the real-time precise point positioning (PPP). In recent years, there has been a rapid development in the BeiDou Navigation Satellite System (BDS), and the constellation of global BDS (BDS-3) has been fully deployed. In addition to the regional BDS (BDS-2) constellation, the real-time stream CLK93 has started to support the BDS-3 constellation, indicating that the real-time PPP processing involving BDS-3 observations is feasible. In this study, the global positioning performance of real-time PPP with BDS-3/BDS-2 observations is initially evaluated using the datasets from 147 stations. In the east, north and upward directions, positioning accuracy of 1.8, 1.2 and 2.5 cm in the static mode, and of 6.7, 5.1 and 10.4 cm in the kinematic mode can be achieved for the BDS-3/BDS-2 real-time PPP, respectively, while the corresponding convergence time with a threshold of 10 cm is 32.9, 23.7 and 32.8 min, and 66.9, 42.9 and 69.1 min in the two modes in the three directions, respectively. To complete this, the availability of BDS-3/BDS-2 constellations, the quality of BDS-3/BDS-2 real-time precise satellite products, and the BDS-3/BDS-2 post-processed PPP solutions are also analyzed. For comparison, the results for the GPS are also presented

The Role of NADPH Oxidase in Multi-Walled Carbon Nanotubes-Induced Oxidative Stress and Cytotoxicity in Human Macrophages

Natural Science Foundation of China [30901175]; Science and Technology Innovation Project of Fujian Province for Young Scientific Researchers, China [2008F3097]Recent studies suggest reactive oxygen species (ROS) induced in mammalian cells exposed to multi-walled carbon nanotubes (MWCNTs) could mediate the cytotoxicity. This study was conducted to determine the mechanisms responsible for MWCNTs-induced ROS production in human primary macrophages. Our results showed that superoxide levels were significantly increased in a time-dependent manner in blood monocyte-derived macrophages treated with 100 mu g/ml MWCNTs for 12 h. Concomitantly, MWCNTs induced membrane translocation of the NADPH oxidase subunits p47(phox) and p67(phox), a signature event for NADPH oxidase activation. Pre-incubation with apocynin, a selective inhibitor of NADPH oxidase, prevented both membrane translocation of p47(phox) and superoxide production. Treatment with MWCNTs also resulted in an increased cytotoxicity in human primary macrophages that was significantly attenuated by both apocynin and antioxidants. These findings demonstrate that MWCNTs activate NADPH oxidase in human macrophages, which may contribute to ROS generation in MWCNTs treated-macrophages