Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

Role of DNA recognition receptors in pathogenic mechanism of hepatitis B

As a global disease, hepatitis B still threatens human health. However, the pathogenesis of hepatitis caused by HBV remains unclear. The innate immune system in the liver can detect HBV infection and use every strategy to eliminate the virus. DNA recognition receptors play an important role in this process; they recognize HBV DNA or pgRNA in cytoplasm or nucleus, activate innate immunity through various signaling pathways to produce inflammatory cytokines and interferon, and finally exert their antiviral effect. This article summarizes the DNA recognition receptors involved in inflammation induced by HBV and HBV clearance, elaborates on their detailed pathways, and discusses the issues regarding the role of DNA recognition receptors in liver innate immunity induced by HBV and related perspectives

Effects of Excess Energy Intake on Glucose and Lipid Metabolism in C57BL/6 Mice.

Excess energy intake correlates with the development of metabolic disorders. However, different energy-dense foods have different effects on metabolism. To compare the effects of a high-fat diet, a high-fructose diet and a combination high-fat/high-fructose diet on glucose and lipid metabolism, male C57BL/6 mice were fed with one of four different diets for 3 months: standard chow; standard diet and access to fructose water; a high fat diet; and a high fat diet with fructose water. After 3 months of feeding, the high-fat and the combined high-fat/high-fructose groups showed significantly increased body weights, accompanied by hyperglycemia and insulin resistance; however, the high-fructose group was not different from the control group. All three energy-dense groups showed significantly higher visceral fat weights, total cholesterol concentrations, and low-density lipoprotein cholesterol concentrations compared with the control group. Assays of basal metabolism showed that the respiratory quotient of the high-fat, the high-fructose, and the high-fat/high-fructose groups decreased compared with the control group. The present study confirmed the deleterious effect of high energy diets on body weight and metabolism, but suggested that the energy efficiency of the high-fructose diet was much lower than that of the high-fat diet. In addition, fructose supplementation did not worsen the detrimental effects of high-fat feeding alone on metabolism in C57BL/6 mice

Local Residents’ Perceptions for Ecosystem Services: A Case Study of Fenghe River Watershed

To make environmental management decisions more executive and targeted, it is essential for decision-making to include local residents’ perceptions and preferences for ecosystem services (ES) and biodiversity (BD). This study conducted a questionnaire survey with 386 local residents to explore social perceptions for ES and BD in the Fenghe River watershed. ES contain food from agriculture (AGR), food from livestock (LIV), fresh water (FW), air purification (AP), water purification (WP), water retention (WR), soil retention (SR), aesthetics (AES), recreation (RE), and spirit (SP) in this study. Ranking and Likert scales are combined to identify residents’ preferences for ES and BD. The hypothetical market method is used to identify the willingness to pay for BD and ES. Independent sample T-test, one-way ANOVA, and Spearman correlation are used to analyze preference heterogeneity. The results show that: (1) residents prefer WP, AP, AGR, and FW; (2) 51.3% of respondents are willing to pay a fee for improving ES while 48.7% of respondents are unwilling to pay; (3) residents’ personal and residential factors affect preference heterogeneity. Last, we put forward three management suggestions on controlling environmental pollution, improving residents’ awareness of ES, and establishing a multi-channel fund based on government financial resources for improving ES in the Fenghe River watershed. Integrating stakeholders’ perceptions for ES into decision-making can promote the sustainable development in Fenghe River watershed

Cardiac Aging: From Basic Research to Therapeutics

With research progress on longevity, we have gradually recognized that cardiac aging causes changes in heart structure and function, including progressive myocardial remodeling, left ventricular hypertrophy, and decreases in systolic and diastolic function. Elucidating the regulatory mechanisms of cardiac aging is a great challenge for biologists and physicians worldwide. In this review, we discuss several key molecular mechanisms of cardiac aging and possible prevention and treatment methods developed in recent years. Insights into the process and mechanism of cardiac aging are necessary to protect against age-related diseases, extend lifespan, and reduce the increasing burden of cardiovascular disease in elderly individuals. We believe that research on cardiac aging is entering a new era of unique significance for the progress of clinical medicine and social welfare

Soluble ST2 Plasma Concentrations Predict Mortality in HBV-Related Acute-on-Chronic Liver Failure

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a rapidly progressing and frequently fatal condition. The aim of this study was to determine whether interleukin- (IL-) 33 and soluble ST2 (sST2) were associated with disease severity and mortality in HBV-ACLF. We found that plasma levels of sST2 but not IL-33 were higher in HBV-ACLF patients compared with chronic hepatitis B (CHB) patients and healthy controls. However, plasma levels of IL-33, TNF-α, IFN-γ, and IL-10 did not correlate with sST2 levels. Similarly, immunohistochemistry revealed low IL-33 expression and high ST2 expression in liver sections of patients with HBV-ACLF. Evaluation of dynamic changes of sST2 in HBV-ACLF showed that plasma sST2 levels increased over time in patients who died during the 180-day follow-up but decreased in those who survived. In addition, plasma sST2 level after week 1 correlated with disease severity, as assessed by total bilirubin, prothrombin time, and model for end-stage liver disease score. Results of Kaplan-Meier survival analysis showed that higher sST2 concentration (≥87 ng/mL) at week 3 was associated with poor survival. These findings indicate the potential usefulness of sST2 as a predictor of disease severity and in making treatment decisions for patients with HBV-ACLF

IFI16 is involved in HBV-associated acute-on-chronic liver failure inflammation

Abstract Background Hepatitis B virus (HBV) is a hepatotropic DNA virus, and its DNA may be a potent inflammatory molecule. Interferon-inducible protein 16 (IFI16), a newly discovered DNA sensor, plays an important role in the process of inflammation in viral infections. Our study sought to identify a correlation between IFI16 expression and inflammation in patients with chronic hepatitis B (CHB) and HBV-associated acute-on-chronic liver failure (HBV-ACLF). Methods We performed flow cytometry to measure IFI16 levels in peripheral blood mononuclear cells (PBMC) and used immunohistochemistry and western blotting to measure IFI16 protein levels in liver tissues. The cellular source of IFI16 was detected using double immunofluorescence. All datum were analyzed using SPSS 13.0 and GraphPad Prism 6. Results The number of IFI16+ cells was significantly associated with the degree of inflammation. In detail, the number of IFI16+ cells was higher in livers but lower in PBMCs in HBV-ACLF patients than those in CHB patients and healthy controls. There was no significant difference between CHB patients and healthy controls in numbers of IFI6+ cells in livers and PBMCs. There was no significant relationship between IFI16 expression levels and HBV parameters. Furthermore, IFI16 was expressed in the nucleus of Kupffer cells (KCs), endothelial cells, natural killer cells, dendritic cells, and hepatic stellate cells in healthy donors and CHB patients, but only in the cytoplasm of KCs in the livers of HBV-ACLF patients. Conclusions IFI16 was closely related to the degree of inflammation in CHB and HBV-ACLF patients and may serve as a vital contributor to the pathogeneses of liver damage in HBV-ACLF

Effect of diet modification on lipid accumulation in the liver.

<p>Liver tissue slides were stained with oil red O and photographed under a microscope. Compared with control mice (A), lipid droplets could be detected obviously in the HFR mice (B), HFA mice (C) and HFF mice (D). The length of the scale is 20 μm.</p

Effect of diet modification on lipid metabolism.

<p>The levels of total cholesterol (TC, A), low-density lipoprotein cholesterol (LDL, B), high-density lipoprotein cholesterol (HDL, C) and triglyceride (TG, D) were detected in the control, HFR, HFA and HFF groups. Data are presented as means ± SD (n ≥ 6 in each group). A significant difference was determined by one-way analysis of variance. *P < 0.05 versus control, **P < 0.01 versus control.</p