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Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is highly correlated with metabolic disease. NAFLD results from environmental exposures acting on a susceptible polygenic background. This study performed the largest multiethnic investigation of exonic variation associated with NAFLD and correlated metabolic traits and diseases. An exome array meta-analysis was carried out among eight multiethnic population-based cohorts (n = 16 492) with computed tomography (CT) measured hepatic steatosis. A fixed effects meta-analysis identified five exome-wide significant loci (P < 5.30 × 10-7); including a novel signal near TOMM40/APOE. Joint analysis of TOMM40/APOE variants revealed the TOMM40 signal was attributed to APOE rs429358-T; APOE rs7412 was not associated with liver attenuation. Moreover, rs429358-T was associated with higher serum alanine aminotransferase, liver steatosis, cirrhosis, triglycerides and obesity; as well as, lower cholesterol and decreased risk of myocardial infarction and Alzheimer's disease (AD) in phenome-wide association analyses in the Michigan Genomics Initiative, United Kingdom Biobank and/or public datasets. These results implicate APOE in imaging-based identification of NAFLD. This association may or may not translate to nonalcoholic steatohepatitis; however, these results indicate a significant association with advanced liver disease and hepatic cirrhosis. These findings highlight allelic heterogeneity at the APOE locus and demonstrate an inverse link between NAFLD and AD at the exome level in the largest analysis to date.

Li Wang,1 Nie Hu,1 Zhongjun Jiang,1 Ping Luo,1 Nian Yi,1 Yanhua Chen,2 Ning Zhou,2 Longfei Liu2 1Department of Breast Surgery, Nanhua Hospital, Nanhua University, Hengyang City, Hunan Province, 421002, People’s Republic of China; 2Department of General Surgery, Nanhua Hospital, Nanhua University, Hengyang City, Hunan Province, 421002, People’s Republic of ChinaCorrespondence: Longfei LiuDepartment of General Surgery, Nanhua Hospital, Nanhua University, No. 336, Dongfeng South Road, Hengyang City, Hunan Province, 421002, People’s Republic of ChinaTel +86 0734-8399028Email liulongfei1977@aliyun.comBackground: Patients with cancer have a higher incidence of cardiovascular diseases (CVDs). We aimed to evaluate the relationship between serum human epididymal protein 4 (HE4) levels and cardiovascular events in obese patients with breast cancer.Methods: Serum HE4 levels in 316 obese patients with breast cancer were measured at baseline and then prospectively followed up for approximately 36 months. The prognostic value of serum HE4 for predicting cardiovascular events was analyzed by the Cox proportional hazard model.Results: Serum HE4 was significantly associated with CVD history after adjustment for confounding factors (OR= 1.50; 95% CI 1.23– 3.43; P= 0.038) using multivariable logistic regression analysis. The multivariable Cox proportional hazard analysis suggested that serum HE4 had an independent prognostic value for predicting cardiovascular events in patients with breast cancer (HR=2.21, 95% CI 1.60– 5.13, P< 0.001). Additionally, sensitivity analysis showed that the independent association still existed. Stratified analysis showed that this relationship was not affected by chemoradiotherapy.Conclusion: Serum HE4 is significantly related to cardiovascular events and poses good prognostic value for predicting cardiovascular events in obese patients with breast cancer. Serum HE4 may be a valuable indicator for the early detection of cardiovascular compli

Cropland abandonment strongly affects plant-soil interactions. However, knowledge remains limited about how the production and diversity of plants and soil physicochemical parameters drive changes in soil microbial activity (such as microbial biomass, respiration, and enzyme activity) after cropland abandonment. Here, we investigated a grassland restoration chronosequence (0–30 years) to determine the dynamics of soil microbial biomass, respiration, and enzyme activity in the Loess Hilly, Region (China). Overall, cropland abandonment caused an increase in soil microbial activity primarily in the 0–20 cm soil layers. The metabolic quotient in the 0–10 cm layer decreased linearly with time since abandonment (recovery years). Structural equation models showed that recovery years directly and indirectly affected changes to soil microbial activity. Plant species richness, aboveground biomass, and soil organic carbon explained a large proportion of the variability in soil microbial activity in the 0–20 cm layer. However, the variability in soil microbial activity was mostly explained by plant species richness, belowground biomass, and soil total nitrogen in the 20–50 cm layers. Our results indicate that during recovery after cropland abandonment, changes in soil microbial activity are driven by plant characteristics and soil physicochemical parameters, with different drivers at different soil depths.

With the development of research on novel memristor model and device, neural networks by integrating various memristor models have become a hot research topic recently. However, state-of-the-art works still build such neural networks using drift memristor only. Furthermore, some other related works are only applied to a few individual applications including pattern recognition and edge detection. In this paper, a novel kind of multilayer neural network is proposed, in which diffusion and drift memristor models are applied to construct a system merging image preprocessing and pattern recognition. Specifically, the entire network consists of two diffusion memristive cellular layers for image preprocessing and one drift memristive feedforward layer for pattern recognition. Experimental results show that good recognition accuracy of noisy MNIST is obtained due to the fusion of image preprocessing and pattern recognition. Moreover, owing to high-efficiency in-memory computing and brief spiking encoding methods, high processing speed, high throughput, and few hardware resources of the entire network are achieved., Comment: Accepted by IEEE Transactions on Cognitive and Developmental Systems

Fully memristive spiking-neuron learning framework, which uses drift and diffusion memristor models as axon and dendrite respectively, becomes a hot topic recently with the development of memristor devices. Normally, some other devices like resistor or capacitor are still necessary on recent works of fully memristive learning framework. However, theoretically, one neuron needs axon and dendrite only, which makes technique process simpler and learning framework more similar to biologic brain. In this paper, a fully memristive spiking-neuron learning framework is introduced, in which a neuron structure is just built of one drift and one diffusion memristive models. To verify it merits, a feedforward neural network for pattern recognition and a cellular neural network for edge detection are designed. Experiment results show that compared to other memristive neural networks, our framework's the processing speed is much faster and the hardware resource is saved in pattern recognition due to its simple structure. Further due to the dynamic filtering function of diffusion memristor model in our learning framework, its peak signal noise ratio (PSNR) is much higher than traditional algorithms in edge detection., Comment: Accepted by Neurocomputing

Yanhua Chen,1,* Xu Zhang,2,* Bingdong Zhang,1 Guodong He,2 Lifang Zhou,2 Yubo Xie2 1Department of Anesthesiology, Cardiovascular Institute, 2Department of Anesthesiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China *These authors contributed equally to this work Abstract: Cardiopulmonary bypass (CPB) constitutes one of the primary methodologies pertaining to cardiac surgery. However, this form of surgery can cause damage to the body. Many studies have reported that dexmedetomidine confers cerebral protection. In this study, we aimed to investigate the effect and mechanism of dexmedetomidine on neuronal apoptosis caused by CPB. Here, rats were treated with different doses of dexmedetomidine by intravenous infusion 2 hours after CPB. We observed that dexmedetomidine treatment to rats reduces the S100ß, NSE levels in plasma, and neuronal apoptosis following CPB in a dose-dependent manner. Furthermore, we observed that the beneficial effect of dexmedetomidine treatment following CPB was associated with a reduction in IL6, an inflammatory cytokine in plasma and cortex. Our results suggest that dexmedetomidine provides neuroprotective effects by inhibiting inflammation and reducing neuronal apoptosis. There was a correlation between the protective effect on the brain and the dose of dexmedetomidine. In addition, dexmedetomidine administration inhibits phosphorylation of JAK2 and STAT3 proteins in the hippocampus of rats 2 hours after CPB. Therefore, we speculate that the JAK2–STAT3 pathway plays an important role in the neuroprotective effects of dexmedetomidine following brain injury induced by CPB. Keywords: apoptosis, cardiopulmonary bypass, dexmedetomidine, neuroprotective effect, JAK2, STAT3