Search

APOE encodes a cholesterol transporter, and the ε4 allele is associated with higher circulating cholesterol levels, ß-amyloid burden, and risk of Alzheimer’s disease. Prior studies demonstrated no significant differences in objective or subjective cognitive function for patients receiving the PCSK9 inhibitor evolocumab vs. placebo added to statin therapy. There is some evidence that cholesterol-lowering medications may confer greater cognitive benefits in APOE ε4 carriers. Thus, the purpose of this study was to determine whether APOE genotype moderates the relationships between evolocumab use and cognitive function. APOE-genotyped patients (N = 13,481; 28% ε4 carriers) from FOURIER, a randomized, placebo-controlled trial of evolocumab added to statin therapy in patients with stable atherosclerotic cardiovascular disease followed for a median of 2.2 years, completed the Everyday Cognition Scale (ECog) to self-report cognitive changes from the end of the trial compared to its beginning; a subset (N = 835) underwent objective cognitive testing using the Cambridge Neuropsychological Test Automated Battery as part of the EBBINGHAUS trial. There was a dose-dependent relationship between APOE ε4 genotype and patient-reported memory decline on the ECog in the placebo arm (p = .003 for trend across genotypes; ε4/ε4 carriers vs. non-carriers: OR = 1.46, 95% CI [1.03, 2.08]) but not in the evolocumab arm (p = .50, OR = 1.18, 95% CI [.83,1.66]). However, the genotype by treatment interaction was not significant (p = .30). In the subset of participants who underwent objective cognitive testing with the CANTAB, APOE genotype did not significantly modify the relationship between treatment arm and CANTAB performance after adjustment for demographic and medical covariates, (p’s>.05). Although analyses were limited by the low population frequency of the ε4/ε4 genotype, this supports the cognitive safety of evolocumab among ε4 carriers, guiding future research on possible benefits of cholesterol-lowering medications in people at genetic risk for Alzheimer’s disease.

APOE encodes a cholesterol transporter, and the ε4 allele is associated with higher circulating cholesterol levels, ß-amyloid burden, and risk of Alzheimer's disease. Prior studies demonstrated no significant differences in objective or subjective cognitive function for patients receiving the PCSK9 inhibitor evolocumab vs. placebo added to statin therapy. There is some evidence that cholesterol-lowering medications may confer greater cognitive benefits in APOE ε4 carriers. Thus, the purpose of this study was to determine whether APOE genotype moderates the relationships between evolocumab use and cognitive function. APOE-genotyped patients (N = 13,481; 28% ε4 carriers) from FOURIER, a randomized, placebo-controlled trial of evolocumab added to statin therapy in patients with stable atherosclerotic cardiovascular disease followed for a median of 2.2 years, completed the Everyday Cognition Scale (ECog) to self-report cognitive changes from the end of the trial compared to its beginning; a subset (N = 835) underwent objective cognitive testing using the Cambridge Neuropsychological Test Automated Battery as part of the EBBINGHAUS trial. There was a dose-dependent relationship between APOE ε4 genotype and patient-reported memory decline on the ECog in the placebo arm (p = .003 for trend across genotypes; ε4/ε4 carriers vs. non-carriers: OR = 1.46, 95% CI [1.03, 2.08]) but not in the evolocumab arm (p = .50, OR = 1.18, 95% CI [.83,1.66]). However, the genotype by treatment interaction was not significant (p = .30). In the subset of participants who underwent objective cognitive testing with the CANTAB, APOE genotype did not significantly modify the relationship between treatment arm and CANTAB performance after adjustment for demographic and medical covariates, (p's>.05). Although analyses were limited by the low population frequency of the ε4/ε4 genotype, this supports the cognitive safety of evolocumab among ε4 carriers, guiding future research on possible benefits of cholesterol-lowering medications in people at genetic risk for Alzheimer's disease.

Oil-produced wastewater treatment plants, especially those involving biological treatment processes, harbor rich and diverse microbes. However, knowledge of microbial ecology and microbial interactions determining the efficiency of plants for oil-produced wastewater is limited. Here, we performed 16S rDNA amplicon sequencing to elucidate the microbial composition and potential microbial functions in a full-scale well-worked offshore oil-produced wastewater treatment plant. Results showed that microbes that inhabited the plant were diverse and originated from oil and marine associated environments. The upstream physical and chemical treatments resulted in low microbial diversity. Organic pollutants were digested in the anaerobic baffled reactor (ABR) dominantly through fermentation combined with sulfur compounds respiration. Three aerobic parallel reactors (APRs) harbored different microbial groups that performed similar potential functions, such as hydrocarbon degradation, acidogenesis, photosynthetic assimilation, and nitrogen removal. Microbial characteristics were important to the performance of oil-produced wastewater treatment plants with biological processes.

Understanding the regional relationships between climate change and crop production will benefit strategic decisions for future agricultural adaptation in China. In this study, the combined effects of climatic factors on spring wheat phenophase and grain yield over the past three decades in Inner Mongolia, China, were explored based on the daily climate variables from 1981-2014 and detailed observed data of spring wheat from 1981-2014. Inner Mongolia was divided into three different climate type regions, the eastern, central and western regions. The data were gathered from 10 representative agricultural meteorological experimental stations in Inner Mongolia and analysed with the Agricultural Production Systems Simulator (APSIM) model. First, the performance of the APSIM model in the spring wheat planting areas of Inner Mongolia was tested. Then, the key climatic factors limiting the phenophases and yield of spring wheat were identified. Finally, the responses of spring wheat phenophases and yield to climate change were further explored regionally. Our results revealed a general yield reduction of spring wheat in response to the pronounced climate warming from 1981 to 2014, with an average of 3564 kg·ha-1. The regional differences in yields were significant. The maximum potential yield of spring wheat was found in the western region. However, the minimum potential yield was found in the middle region. The air temperature and soil surface temperature were the optimum climatic factors that affected the key phenophases of spring wheat in Inner Mongolia. The influence of the average maximum temperature on the key phenophases of spring wheat was greater than the average minimum temperature, followed by the relative humidity and solar radiation. The most insensitive climatic factors were precipitation, wind speed and reference crop evapotranspiration. As for the yield of spring wheat, temperature, solar radiation and air relative humidity were major meteorological factors that affected in the eastern and western Inner Mongolia. Furthermore, the effect of the average minimum temperature on yield was greater than that of the average maximum temperature. The increase of temperature in the western and middle regions would reduce the spring wheat yield, while in the eastern region due to the rising temperature, the spring wheat yield increased. The increase of solar radiation in the eastern and central regions would increase the yield of spring wheat. The increased air relative humidity would make the western spring wheat yield increased and the eastern spring wheat yield decreased. Finally, the models describing combined effects of these dominant climatic factors on the maturity and yield in different regions of Inner Mongolia were used to establish geographical differences. Our findings have important implications for improving climate change impact studies and for local agricultural production to cope with ongoing climate change.

The association between Human Leukocyte Antigen (HLA) class II and rheumatoid arthritis (RA) has been extensively studied, but few reported DR-DQ haplotype. Here we investigated the association of HLA-DRB1, DQA1, DQB1, and DR-DQ haplotypes with RA susceptibility and with anti-CCP antibodies in 281 RA patients and 297 control in Han population. High-resolution genotyping were performed. The HLA-DRB1 shared epitope (SE)-encoding allele *0405 displayed the most significant RA association (P = 1.35×10(-6)). The grouped DRB1 SE alleles showed great association with RA (P = 3.88×10(-13)). The DRB1 DRRAA alleles displayed significant protective effects (P = 0.021). The SE-dependent DR-DQ haplotype SE-DQ3/4/5 remained strong association with both anti-CCP -positive (P = 3.71×10(-13)) and -negative RA (P = 3.89×10(-5)). Our study revealed that SE alleles and its haplotypes SE-DQ3/4/5 were highly associated with RA susceptibility in Han population. The SE-DQ3/4/5 haplotypes were associated with both anti-CCP positive RA and -negative RA.

[This corrects the article DOI: 10.1371/journal.pone.0041228.].

An improved individual-based forest ecosystem carbon budget model for China (FORCCHN) was applied to investigate the spatial-temporal dynamics of net primary productivity of different forest types in northeastern China. In this study, the forests of northeastern China were categorized into four ecological types according to their habitats and generic characteristics (evergreen broadleaf forest, deciduous broadleaf forest, evergreen needleleaf forest and deciduous needleleaf forest). The results showed that distribution and change of forest NPP in northeastern China were related to the different forest types. From 1981 to 2002, among the forest types in northeastern China, per unit area NPP and total NPP of deciduous broadleaf forest were the highest, with the values of 729.4 gC/(m(2)•yr) and 106.0 TgC/yr, respectively, followed by mixed broadleaf- needleleaf forest, deciduous needleleaf forest and evergreen needleleaf forest. From 1981 to 2002, per unit area NPP and total NPP of different forest types in northeastern China exhibited significant trends of interannual increase, and rapid increase was found between the 1980s and 1990s. The contribution of the different forest type's NPP to total NPP in northeastern China was clearly different. The greatest was deciduous broadleaf forest, followed by mixed broadleaf- needleleaf forest and deciduous needleleaf forest. The smallest was evergreen needleleaf forest. Spatial difference in NPP between different forest types was remarkable. High NPP values of deciduous needleleaf forest, mixed broadleaf- needleleaf forest and deciduous broadleaf forest were found in the Daxing'anling region, the southeastern of Xiaoxing'anling and Jilin province, and the Changbai Mountain, respectively. However, no regional differences were found for evergreen needleleaf NPP. This study provided not only an estimation NPP of different forest types in northeastern China but also a useful methodology for estimating forest carbon storage at regional and global levels.

MKT-077, a rhodacyanine dye, was shown to produce cancer specific cell death. However, complications prevented the use of this compound beyond clinical trials. Here we describe YM-1, a derivative of MKT-077. We found that YM-1 was more cytotoxic and localized differently than MKT-077. YM-1 demonstrated this cytotoxicity across multiple cancer cell lines. This toxicity was limited to cancer cell lines; immortalized cell models were unaffected. Brief applications of YM-1 were found to be non-toxic. Brief treatment with YM-1 restored tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cell model. This effect is potentially due to altered estrogen receptor alpha phosphorylation, an outcome precipitated by selective reductions in Akt levels (Akt/PKB). Thus, modifications to the rhodocyanine scaffold could potentially be made to improve efficacy and pharmacokinetic properties. Moreover, the impact on tamoxifen sensitivity could be a new utility for this compound family.

Dendritic cell immunoreceptor (DCIR) has been implicated in development of autoimmune disorders in rodent and DCIR polymorphisms were associated with anti-citrullinated proteins antibodies (ACPA)-negative rheumatoid arthritis (RA) in Swedish Caucasians. This study was undertaken to further investigate whether DCIR polymorphisms are also risk factors for the development of RA in four Asian populations originated from China and Malaysia.We genotyped two DCIR SNPs rs2377422 and rs10840759 in Han Chinese population (1,193 cases, 1,278 controls), to assess their association with RA. Subsequently, rs2377422 was further genotyped in three independent cohorts of Malaysian-Chinese subjects (MY_Chinese, 254 cases, 206 controls), Malay subjects (MY_ Malay, 515 cases, 986 controls), and Malaysian-Indian subjects (MY_Indian, 378 cases, 285 controls), to seek confirmation of association in various ethnic groups. Meta-analysis was preformed to evaluate the contribution of rs2377422 polymorphisms to the development of ACPA-negative RA in distinct ethnic groups. Finally, we carried out association analysis of rs2377422 polymorphisms with DCIR mRNA expression levels.DCIR rs2377422 was found to be significantly associated with ACPA -negative RA in Han Chinese (OR 1.92, 95% CI 1.27-2.90, P=0.0020). Meta-analysis confirms DCIR rs2377422 as a risk factor for ACPA-negative RA across distinct ethnic groups (OR(overall) =1.17, 95% CI 1.06-1.30, P=0.003). The SNP rs2377422 polymorphism showed significant association with DCIR mRNA expression level, i.e. RA-risk CC genotype exhibit a significant increase in the expression of DCIR (P=0.0023, Kruskal-Wallis).Our data provide evidence for association between DCIR rs2377422 and RA in non-Caucasian populations and confirm the influence of DCIR polymorphisms on RA susceptibility, especially on ACPA-negative RA.