Treatment with the Prolyl Hydroxylase Inhibitor JNJ Promotes Abdominal Aortic Aneurysm Progression in Diabetic Mice.

OBJECTIVE: Prolyl hydroxylase domain containing proteins (PHD) rigorously regulate intracellular hypoxia inducible factor-1 (HIF-1) protein expression and activity. Diabetes impairs PHD activity and attenuates abdominal aortic aneurysm (AAA) progression. The extent to which dysregulated PHD activity contributes to diabetes mediated AAA suppression remains undetermined. METHODS: AAAs were induced in diabetic and non-diabetic male C57BL/6J mice via intra-aortic elastase infusion. A PHD inhibitor (JNJ-42041935, aka "JNJ", 150 mmol/kg) or vehicle alone was administered daily starting one day prior to AAA induction for 14 days. Influences on AAA progression was assessed via ultrasonography and histopathology. Expression of aortic HIF-1α, three of its target genes and macrophage derived mediators were assayed via quantitative reverse transcription polymerase chain reaction. Aneurysmal sections from AAA patients with and without diabetes (two patients in each group) were immunostained for HIF-1α and vascular endothelial growth factor (VEGF)-A. RESULTS: Expression of HIF-1α target genes (erythropoietin, VEGF-A, and glucose transporter-1) was reduced by 45% - 95% in experimental diabetic aortas. Diameter enlargement was similarly limited, as were mural elastin degradation, leukocyte infiltration, and neo-angiogenesis (reduced capillary density and length) on histopathology. Pre-treatment with JNJ prior to AAA initiation augmented aortic HIF-1α target gene expression and aneurysm progression in diabetic mice, along with macrophage VEGF-A and matrix metalloproteinase 2 mRNA expression. No differences were noted in HIF-1α or VEGF-A expression on aortic immunohistochemical staining of human aortic tissue as a function of diabetes status. CONCLUSION: Small molecule PHD inhibitor treatment reduces or offsets impairment of experimental AAA progression in hyperglycemic mice, highlighting the potential contribution of dysregulated PHD activity to diabetes mediated aneurysm suppression.

Glucocorticoid therapy reduces ocular hypertension in active moderate-severe thyroid-associated orbitopathy.

PURPOSE: Ocular hypertension (OHT) is an important clinical feature of thyroid-associated orbitopathy (TAO).While the prevalence and outcome of OHT in TAO remains unclear. This study investigates this in moderate-severe active TAO. METHODS: Sixty-eight patients with active moderate-severe TAO were recruited, 49 of whom were treated with 12-week GC therapy.The clinical and biochemical parameters were collected.Treatment outcomes were evaluated after GC therapy. RESULTS: The prevalence of OHT was 44.85% in moderate-severe active TAO patients,including 81.97% of mild hypertension, 13.11% of moderate hypertension and 4.92% of severe hypertension. Clinical and biochemical parameters had no significant difference between OHT patients and non-OHT patients,such as age, sex distributions, smoking status, the kind and the duration of thyroid disease,the duration of eye symptoms and the level of FT3,FT4,TSH, TR-Ab, and Tpo-Ab, Tg-Ab(all P > 0.05). After GC therapy,the intraocular pressure(IOP) in OHT eyes decreased significantly (P < 0.05), while IOP in non-OHT eyes remained unchanged (P > 0.05).There was no significant difference in CAS and the effective rate of GC therapy between OHT eyes and non-OHT eyes (P > 0.05). CONCLUSION: In moderate-severe active TAO, the prevalence of OHT was 44.85%, most of which were mild hypertension.OHT was relieved by GC therapy,which had no effect on the efficacy of GC therapy.Our results will enhance physicians' confidence in GC therapy.

Recovery of heavy metals from industrial wastewater using bioelectrochemical system inoculated with novel Castellaniella species.

Water pollution is a global issue that has drastically increased in recent years due to rapid industrial development. Different technologies have been designed for the removal of pollutants from wastewater. However, most of these techniques are expensive, generate new waste, and focus solely on metal removal instead of metal recovery. In this study, novel facultative exoelectrogenic strains designated Castellaniella sp. A5, Castellaniella sp. B3, and Castellaniella sp. A3 were isolated from a microbial fuel cell (MFC). These isolates were utilized as pure and mixed culture inoculums in a bioelectrochemical system (BES) to produce bioelectricity and treat simulated industrial wastewater. A single-chamber MFC inoculated with the mixed culture attained the highest electricity generation (i.e., 320 mW/m2 power density and 3.19 A/m2 current density), chemical oxygen demand removal efficiency (91.15 ± 0.05%), and coulombic efficiency (54.81 ± 4.18%). In addition, the BES containing biofilms of the mixed culture achieved the highest Cu, Cr, and Cd removal efficiencies of 99.89 ± 0.07%, 99.59 ± 0.53%, and 99.91 ± 0.04%, respectively. The Cr6+ and Cu2+ in the simulated industrial wastewater were recovered via microbial electrochemical reduction as Cr3+ and Cu0, respectively. However, Cd2+ precipitated as Cd (OH)2 or CdCO3 on the surface of the cathodes. These results suggest that a mixed culture inoculum of Castellaniella sp. A5, Castellaniella sp. B3, and Castellaniella sp. A3 has great potential as a biocatalyst in BES for heavy metals recovery from industrial wastewater.

Enhancing microbial fuel cell performance using anode modified with Fe3O4 nanoparticles.

Low electricity generation efficiency is one of the key issues that must be addressed for the practical application of microbial fuel cells (MFCs). Modification of microbial electrode materials is an effective method to enhance electron transfer. In this study, magnetite (Fe3O4) nanoparticles synthesized by co-precipitation were added to anode chambers in different doses to explore its effect on the performance of MFCs. The maximum power density of the MFCs doped with 4.5 g/L Fe3O4 (391.11 ± 9.4 mW/m2) was significantly increased compared to that of the undoped MFCs (255.15 ± 24.8 mW/m2). The COD removal efficiency of the MFCs increased from 85.8 ± 2.8% to 95.0 ± 2.1%. Electrochemical impedance spectroscopy and cyclic voltammetry tests revealed that the addition of Fe3O4 nanoparticles enhanced the biocatalytic activity of the anode. High-throughput sequencing results indicated that 4.5 g/L Fe3O4 modified anodes enriched the exoelectrogen Geobacter (31.5%), while control MFCs had less Geobacter (17.4%). Magnetite is widely distributed worldwide, which provides an inexpensive means to improve the electrochemical performance of MFCs.

Volatile Organic Compounds to Identify Infectious (Bacteria/Viruses) Diseases of the Central Nervous System: A Pilot Study.

BACKGROUND: Central nervous system (CNS) infectious diseases are common diseases in emergency rooms and neurology departments. CNS pathogen identification methods are time consuming and expensive and have low sensitivity and poor specificity. Some studies have shown that bacteria and viruses can produce specific volatile organic compounds (VOCs). The aim of this study is to find potential biomarkers by VOC analysis of cerebrospinal fluid (CSF) in patients with bacterial and viral meningitis/encephalitis (ME). METHODS: CSF samples from 16 patients with bacterial ME and 42 patients with viral ME were collected, and solid-phase microextraction combined with gas chromatography-mass spectrometry was used to analyze the metabolites in the CSF. RESULTS: There are 2 substances (ethylene oxide and phenol) that were found to be different between the 2 groups. Ethylene oxide was significantly greater in the group of bacterial ME patients than in the viral ME group of patients (p < 0.05). In addition, phenol was remarkably increased in the group of ME patients compared with the bacterial ME patients (p < 0.05). CONCLUSIONS: Ethylene oxide and phenol may be potential biomarkers to distinguish bacterial ME and viral ME. VOC analysis of CSF may be used as a supporting tool for clinical diagnosis.

Inhibition of VEGF (Vascular Endothelial Growth Factor)-A or its Receptor Activity Suppresses Experimental Aneurysm Progression in the Aortic Elastase Infusion Model.

OBJECTIVE: We examined the pathogenic significance of VEGF (vascular endothelial growth factor)-A in experimental abdominal aortic aneurysms (AAAs) and the translational value of pharmacological VEGF-A or its receptor inhibition in aneurysm suppression. Approaches and Results: AAAs were created in male C57BL/6J mice via intra-aortic elastase infusion. Soluble VEGFR (VEGF receptor)-2 extracellular ligand-binding domain (delivered in Ad [adenovirus]-VEGFR-2), anti-VEGF-A mAb (monoclonal antibody), and sunitinib were used to sequester VEGF-A, neutralize VEGF-A, and inhibit receptor tyrosine kinase activity, respectively. Influences on AAAs were assessed using ultrasonography and histopathology. In vitro transwell migration and quantitative reverse transcription polymerase chain reaction assays were used to assess myeloid cell chemotaxis and mRNA expression, respectively. Abundant VEGF-A mRNA and VEGF-A-positive cells were present in aneurysmal aortae. Sequestration of VEGF-A by Ad-VEGFR-2 prevented AAA formation, with attenuation of medial elastolysis and smooth muscle depletion, mural angiogenesis and monocyte/macrophage infiltration. Treatment with anti-VEGF-A mAb prevented AAA formation without affecting further progression of established AAAs. Sunitinib therapy substantially mitigated both AAA formation and further progression of established AAAs, attenuated aneurysmal aortic MMP2 (matrix metalloproteinase) and MMP9 protein expression, inhibited inflammatory monocyte and neutrophil chemotaxis to VEGF-A, and reduced MMP2, MMP9, and VEGF-A mRNA expression in macrophages and smooth muscle cells in vitro. Additionally, sunitinib treatment reduced circulating monocytes in aneurysmal mice. CONCLUSIONS: VEGF-A and its receptors contribute to experimental AAA formation by suppressing mural angiogenesis, MMP and VEGF-A production, myeloid cell chemotaxis, and circulating monocytes. Pharmacological inhibition of receptor tyrosine kinases by sunitinib or related compounds may provide novel opportunities for clinical aneurysm suppression.

Urotensin II and urantide exert opposite effects on the cellular components of atherosclerotic plaque in hypercholesterolemic rabbits.

Increasing levels of plasma urotensin II (UII) are positively associated with atherosclerosis. In this study we investigated the role of macrophage-secreted UII in atherosclerosis progression, and evaluated the therapeutic value of urantide, a potent competitive UII receptor antagonist, in atherosclerosis treatment. Macrophage-specific human UII-transgenic rabbits and their nontransgenic littermates were fed a high cholesterol diet for 16 weeks to induce atherosclerosis. Immunohistochemical staining of the cellular components (macrophages and smooth muscle cells) of aortic atherosclerotic lesions revealed a significant increase (52%) in the macrophage-positive area in only male transgenic rabbits compared with that in the nontransgenic littermates. However, both male and female transgenic rabbits showed a significant decrease (45% in males and 31% in females) in the smooth muscle cell-positive area compared with that of their control littermates. The effects of macrophage-secreted UII on the plaque cellular components were independent of plasma lipid level. Meanwhile the wild-type rabbits were continuously subcutaneously infused with urantide (5.4 µg· kg-1· h-1) using osmotic mini-pumps. Infusion of urantide exerted effects opposite to those caused by UII, as it significantly decreased the macrophage-positive area in male wild-type rabbits compared with that of control rabbits. In cultured human umbilical vein endothelial cells, treatment with UII dose-dependently increased the expression of the adhesion molecules VCAM-1 and ICAM-1, and this effect was partially reversed by urantide. The current study provides direct evidence that macrophage-secreted UII plays a key role in atherogenesis. Targeting UII with urantide may promote plaque stability by decreasing macrophage-derived foam cell formation, which is an indicator of unstable plaque.

Prevalence of low lean mass in patients with adult growth hormone deficiency with or without low-dose growth hormone therapy.

OBJECTIVE: The importance of muscle mass has been emphasized in various studies, and growth hormone (GH) deficiency is tightly associated with lean mass loss. Therefore, we aimed to investigate the prevalence of low lean mass in patients with adult growth hormone deficiency (AGHD) who received or did not receive GH therapy. METHODS: In this retrospective study, we included patients diagnosed with AGHD by using the insulin tolerance test (ITT) in our hospital. Patients without completed follow-up data were excluded, and data for 56 patients were analysed. Twenty-six patients who had received GH therapy for more than 6 months, based on the medical record, were included in the GH group and received recombinant human growth hormone (rhGH) at a dose of 0.5 IU/d. Thirty patients who had not previously received GH treatment were included in the non-GH group. Many anthropometric and blood biochemical indicators were measured. Body composition was measured on a dual-energy X-ray-absorptiometry (DXA) scanner. Low lean mass was defined as a skeletal muscle index (SMI) <7.0 kg/m2 in males or 5.7 kg/m2 in females. Statistical analyses were performed using GraphPad Prism 5.0. RESULTS: Compared to the non-GH group, the patients who received GH therapy had significantly lower total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and fasting plasma glucose (FPG). The percentage of patients with low lean mass in GH and non-GH groups was 30.77% and 60%, respectively. The percentage of total lean was lower in the GH group than in the non-GH group, but the difference in total lean mass was not statistically significant. Conversely, patients with GH treatment had significantly lower fat mass and percentage than non-GH-treated patients (P < 0.05). The GH group had significantly higher serum levels of both IGF-1 and IGFBP3. Moreover, both IGF-1 and IGFBP3 were significantly correlated with SMI (r2  = 0.275, P = 0.003, and r2  = 0.138, P = 0.005, respectively). CONCLUSIONS: Our data showed that AGHD patients who received low-dose GH treatment had a lower prevalence of low lean mass than those who did not receive GH treatment. Patients with GH treatment had significantly lower cardiovascular risk factors, especially the lipid profile.

Release of volatile organic compounds (VOCs) from colorectal cancer cell line LS174T.

Colorectal cancer (CRC) is the third most common cancer worldwide. To date, no non-invasive and specific biomarkers have been identified for the diagnosis of CRC. The analysis of volatile organic compounds (VOCs) is attracting increasing attention and provides the possibility of a non-invasive diagnosis. Solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) have been used to analyze the VOCs released from the headspace gas of LS174T (Dukes' type B colorectal adenocarcinoma) cells, arsenic trioxide (ATO)-treated LS174T cells and the blood from tumor-bearing mice. The data were processed using principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA), which showed that the levels of decanal, 2,4-dimethyl- heptane, and twelve other metabolites were significantly greater in the headspace gas of the LS174T cells and blood of tumor-bearing mice. Additionally, in vivo experiments indicated that formic acid, ethenyl ester and p-trimethylsilyloxyphenyl-(trimethylsilyloxy)trimethylsilylacrylate were consumed during tumor growth. In conclusion, VOCs such as 1-methoxy-hexane and 2,4-dimethyl-heptane could be useful diagnostic markers for CRC. Further research should focus on the potential metabolic pathways associated with these profiles.

EXPOSURE TO THE CHINESE FAMINE IN EARLY LIFE AND THE THYROID FUNCTION AND NODULES IN ADULTHOOD.

Objective: Previous studies found that exposure to famine was associated with a higher risk of metabolic syndrome and fatty liver in adult women. In the present study, we investigated the relationship between exposure to the Chinese famine in early life and thyroid function and nodules in adulthood. Methods: We retrospectively analyzed the data of subjects who underwent routine physical check-up in the Public Health Center of our hospital in 2017. Subjects were divided into 3 groups: post-, pre-, and nonexposed groups. The basal metabolic rate (BMR) was estimated by the revised Harris-Benedict formulation. The serum levels of thyroid hormones were detected. Thyroid ultrasonography was performed by experienced technicians. The diagnosis of thyroid nodules was according to the Thyroid Imaging Reporting and Data System (TI-RADS). Results: Compared to nonexposed subjects, the postnatally exposed subjects had a significantly lower level of thyroxine, and statistically higher ultrasensitive thyroid stimulating hormone (P<.05). There was no significant difference in thyroid autoimmune antibodies between groups exposed to the famine and the nonexposed group (P>.05). There were no statistical differences in heart rate and BMR among these groups (P>.05). Exposure to the famine did not affect either the numbers of thyroid nodules, the TI-RADS score of thyroid nodules, or the maximal diameters of thyroid nodules. Conclusion: Our results indicate a significant association between famine exposure in early life and down-regulated thyroid function in adulthood. Postnatal famine exposure may be more vulnerable to nutrient deficiency and lead to restricted thyroid development in later life. Abbreviations: BMR = basal metabolic rate; FT3 = free triiodothyronine; FT4 = free thyroxine; IDD = iodine deficiency disorder; T3 = triiodothyronine; T4 = thyroxine; TG-Ab = thyroglobulin antibody; TI-RADS = Thyroid Imaging Reporting and Data System; uTSH = ultrasensitive thyroid stimulating hormone.

CORRELATION OF INCREASED SERUM ADIPSIN WITH INCREASED CARDIOVASCULAR RISKS IN ADULT PATIENTS WITH GROWTH HORMONE DEFICIENCY.

Objective: Adult growth hormone deficiency (AGHD) patients have an increased cardiovascular morbidity and mortality. Adipsin is an adipokine that is significantly correlated with metabolic disease, especially in people with obesity. The objective of our study was to compare AGHD patients with healthy subjects to evaluate whether adipsin levels are closely related to glycolipid metabolism and cardiovascular risks in AGHD patients. Methods: Our study included 88 AGHD patients and 88 age-, weight-, and body mass index (BMI)-matched healthy subjects. Anthropometric parameters such as BMI, waist circumference, and blood pressure were measured. Biochemical indicators such as serum adipsin, lipids, and fasting insulin levels were determined. Results: Adipsin levels in AGHD patients were significantly increased compared to levels of the control group (11,567.29 ng/mL, interquartile [9,856.46 to 13,360.60 ng/mL]) versus (9,127.86 ng/mL, interquartile [8,061.82 to 10,647.06 ng/mL], P = .000). Increased serum adipsin levels are correlated with cardiovascular risk factors such as a higher waist-to-hip ratio, serum lipids levels, and insulin resistance. Adipsin levels were inversely related to insulin-like growth factor 1 (IGF-1) (r = -0.6363, P<.0001) and insulin-like growth factor binding protein 3 levels (r = -0.498, P<.0001). The odds ratio (OR) for AGHD in the highest quartile was found to be 4.491 times the ratio in the lowest quartile (OR = 4.491, P = .048). Additionally, adipsin was found to be the most independent factor to influence IGF-1 levels in AGHD subjects. Conclusion: The serum levels of adipsin were significantly correlated with glucolipid metabolism disorder with a growth hormone deficiency status. Furthermore, serum levels of adipsin might be a good marker for the occurrence and development of cardiovascular diseases in AGHD patients. Abbreviations: AGHD = adult growth hormone deficiency; ASCVD = atherosclerotic cardiovascular disease; BMI = body mass index; DBP = diastolic blood pressure; FINS = fasting insulin; FPG = fasting plasma glucose; GH = growth hormone; HOMA-IR = homeostatic model to assess insulin resistance index; hsCRP = high-sensitivity C-reactive protein; IGF-1 = insulin-like growth factor 1; IGFBP-3 = insulin-like growth factor binding protein 3; LAP = lipid accumulation products; LDL = low-density lipoprotein; SBP = systolic blood pressure; TC = total cholesterol; TG = triglycerides; WC = waist circumference; WHR = waist-to-hip ratio; OR = odds ratio.

Effect of IL-21 on the Balance of Th17 Cells/Treg Cells in the Pathogenesis of Graves' Disease.

Graves' disease (GD) is a common organ-specific autoimmune disease, and its pathogenesis is still unclear. The aim of this study is to investigate the role of interleukin (IL)-21 in the regulation of Th17/Treg cells in GD. We recruited 28 newly diagnosed GD patients, 27 GD patients in remission (eGD), and 24 normal controls (NC). Thyroid function and autoantibodies were evaluated by electrochemical luminescence. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured with or without recombinant human interleukin-21 (rhIL-21), and mRNA and protein levels were quantified by real-time PCR and ELISA, respectively. Compared with those in the eGD and control groups, the thyroid function indexes and autoantibodies levels were significantly different in the GD group (P < 0.05). Without rhIL-21 stimulation, the expression levels of retinoid-related orphan gamma t (RORγt), IL-17, IL-22, forkhead box protein P3 (Foxp3) and IL-10 mRNA and the IL-10 and IL-22 proteins were significantly higher in the GD group than those in the eGD and control groups (P < 0.05). rhIL-21 stimulation increased the RORγt, IL-17, and IL-22 mRNA levels and IL-22 protein levels and decreased the Foxp3 and IL-10 mRNA levels and IL-10 protein levels (P < 0.05) in the GD group. In conclusion, our analyses demonstrated that IL-21 might induce the differentiation of CD4+ T cells to Th17 cells and reduce Treg cell differentiation, which could contribute to activation of the downstream immune response and the pathogenesis of GD.

Gender-specific association of serum uric acid levels and cardio-ankle vascular index in Chinese adults.

BACKGROUND: Little is known about the relationship between serum uric acid (SUA) and cardio-ankle vascular index (CAVI) in Chinese population. Therefore, we aimed to investigate the gender difference in the association of SUA and CAVI in a southwestern Chinese population. METHODS: Data were obtained from subjects via routine physical examinations in the Public Health Center of our hospital between 2011 and 2014 in Chongqing. The data included completed anthropometry and blood biochemical indicators. The CAVI were recorded using an automatically VaseraVS-1000 vascular screening system. RESULTS: We found females with hyperuricemia (HUA) had significantly higher CAVI than women with normal SUA (8.45 ± 1.40 vs 7.67 ± 1.15, P<0.05). Then we defined high CAVI as CAVI≥9 m/s, and compared the percentage of high CAVI, we found women with HUA had higher percentage of high CAVI than women with normal SUA (26.83% vs 9.38%, P<0.05). Those differences were not significant in males. Also, the logistic regression analysis found age and hypertension were major independent risk factors associated with high CAVI in both genders. HUA and hyperglycemia were independently associated with high CAVI in females with an OR of 3.65, 95%CI (1.37-9.73) and 3.02, 95%CI (1.38-6.63) respectively. However, these significant associations were not be found in males. CONCLUSIONS: Our data showed positive associations between elevated SUA levels and higher CAVI risk in the inland Chinese females, but not in males. The reason for the gender differences were still unclear, sex hormones may play a role. Further prospective studies including detailed personal information and multicenter were required.

MST-4 and TRAF-6 expression in the peripheral blood mononuclear cells of patients with Graves' disease and its significance.

BACKGROUND: MST-4 and TRAF-6 are involved in the regulation of inflammatory and immune responses. However, whether they participate in the pathogenesis of Graves' disease (GD) has not yet been reported. Therefore, the purpose of this study was to investigate the expression of MST-4 and TRAF-6 in the peripheral blood of patients with GD to understand their role in the pathogenesis of GD. METHODS: Thirty newly diagnosed GD patients, 24 GD patients in remission (eGD) and 30 normal controls (NC) were recruited. Thyroid function and autoantibody levels were determined using a chemiluminescence immunoassay. Peripheral blood mononuclear cells (PBMCs) were extracted, and MST-4 and TRAF-6 mRNA and protein levels were determined using real-time PCR and Western blotting, respectively. RESULTS: 1. Thyroid function in the GD group was significantly different from that in the eGD and NC groups (P < 0.05); however, there was no difference in thyroid function between the eGD group and the NC group (P > 0.05). The autoantibody levels in the NC group were significantly different from those in the GD and eGD groups (P < 0.05); however, the difference in the levels between the GD group and eGD group was not statistically significant (P > 0.05). 2. The MST-4 and TRAF-6 mRNA and protein levels in the GD group were significantly lower than those in the NC group (P < 0.05); however, there were no differences in mRNA and protein levels between the GD group and the eGD group or between the eGD group and the NC group (P > 0.05). 3. The correlation between the MST-4 and TRAF-6 mRNA and protein levels was not significant. However, there was a significant correlation between the TRAF-6 mRNA and TPO Ab levels in the eGD group and between the TRAF-6 mRNA and TR Ab levels in the NC group. CONCLUSION: The MST-4 and TRAF-6 mRNA and protein levels were lower in the GD group than in the NC group, suggesting that MST-4 and TRAF-6 may be important in the pathogenesis of GD. Whether MST-4 influences the innate immune response through TRAF-6 and thus regulates the imbalance in downstream effector T cells requires further study. Investigating the expression of MST-4 and TRAF-6 in GD can provide a new perspective and targets for further study of the upstream mechanism responsible for effector T cell imbalance.

Serum uric acid and non-alcoholic fatty liver disease in non-obesity Chinese adults.

BACKGROUND: Previous studies found elevated serum uric acid (SUA) was associated with the development or progression of non-alcoholic fatty liver disease (NAFLD) in general population; in this study we aim to investigate the association of SUA and the severity of NAFLD based on grade of fatty liver on ultrasonography in non-obese subjects. METHODS: Data were obtained from subjects via routine physical examinations in the Public Health Center of our hospital between 2011 and 2014. The data included completed anthropometry and blood biochemical indicators and the results of abdominal ultrasound. The diagnosis of NAFLD was according to the clinical diagnosis of the Guidelines for the diagnosis and treatment of nonalcoholic fatty liver disease in 2008. RESULTS: In total, 95,924 subjects were analyzed in this study. The prevalence rate of lean-NAFLD was 8.16%, among which 7.58% had mild steatosis, and 0.58% had moderate and severe steatosis. The prevalence of fatty liver was increased progressively with SUA. Among which the prevalence of mild fatty liver from Q1 to Q4 were 10.33%, 18.39%, 23.11% and 25.93%; the prevalence of moderate and severe fatty liver from Q1 to Q4 were 1.06%, 2.82%, 5.05% and 7.27%. Lean-subjects with hyperuricemia had an OR of 1.718 (95% CI 1.622-1.820) to have NAFLD, after adjusted for other metabolic disorders. The area under curve (AUC) for detecting mild fatty liver based on SUA was 0.70; and the AUC for detecting moderate and severe fatty liver based on SUA was 0.78. CONCLUSIONS: Our data showed positive associations between elevated SUA levels and lean-NAFLD risk in the inland Chinese adults, independent of other metabolic factors. Our study also suggests that SUA could be considered as a simple and non-invasive method to follow up patients with lean-NAFLD.

The Great Chinese Famine Exposure in Early Life and the Risk of Nonalcoholic Fatty Liver Disease in Adult Women.

INTRODUCTION AND AIM: Previous studies found famine exposure was associated with a higher risk of metabolic syndrome (MetS). In the study, we investigated the relationship between Chinese famine exposure and the risk of nonalcoholic fatty liver disease (NAFLD) in adult women. MATERIALS AND METHODS: Data were obtained from subjects via routine physical examinations in the Public Health Center of our hospital between 2011 and 2014. Women were categorized into the following three groups: control, prenatally exposed, and postnatally exposed. Hepatic steatosis was diagnosed according to the guidelines established for the diagnosis and treatment of NAFLD. RESULTS: The prevalence rates of NAFLD among non-exposed, prenatally, and postnatally exposed women were 17.3, 23.0, and 22.9%, respectively. Pre-exposed and postnatally exposed women had higher risks of NAFLD, exhibiting ORs (95% CI) of 1.33 (1.04-1.70) and 1.26 (1.03-1.55), respectively. Prenatally, but not postnatally, exposed women had significantly higher risks of having abnormal alanine aminotransferase (ALT), with ORs of 1.30 (1.05-1.61). CONCLUSIONS: The results indicate a significant association between famine exposure in early life and the risk of NAFLD in adult women. Prenatally exposed women displayed higher risks of NAFLD and mild, moderate and severe steatosis.

Genetic analysis and gene mapping of the glabrous leaf and hull mutant glr3 in rice (Oryza sativa L.).

We obtained a glabrous leaf and hull mutant from a population of radiation mutagenesis of an indica rice cultivar R401. The mutant produced smooth leaves and hairless glumes under normal growth conditions. An F2 population was developed from a cross between a japonica cultivar Nipponbare and the glabrous leaf and hull mutant. By investigating the performance of the F2 population, we found that the mutant phenotype was controlled by a single recessive gene, temporarily designated GLR3. Bulked segregant analysis (BSA) based on the F2 mapping population revealed that GLR3 is located on chromosome 6. By analyzing 417 typical glabrous leaf F2 plants using molecular markers, GLR3 was mapped to a 0.2 cM interval between InDel markers ID27101 and ID27199, and the physical distance between the two markers is 98 kb. Thus we have mapped the gene GLR3, and our work will provide basis for future mechanistic analysis of GLR3 function.

Identification of Mycoviruses in the Pathogens of Fragrant Pear Valsa Canker from Xinjiang in China.

As a common disease, canker seriously affects the yield and quality of fragrant pear due to the lack of effective control measures. Some fungi have been reported to harbor rich reservoirs of viral resources, and some mycoviruses can be used as biocontrol agents against plant diseases. In this study, 199 isolates were obtained from diseased branches of fragrant pear in the main production areas of Xinjiang. Among them, 134 belonged to Valsa spp., identified using morphological and molecular biological techniques, in which V. mali was the dominant species. The mycoviruses in Valsa spp. were further identified using metatranscriptomic sequencing and RT-PCR. The results revealed that a total of seven mycoviruses were identified, belonging to Botourmiaviridae, Endornaviridae, Fusariviridae, Hypoviridae, Mitoviridae, and Narnaviridae, among which Phomopsis longicolla hypovirus (PlHV) was dominant in all the sample collection regions. The Cryphonectria hypovirus 3-XJ1 (CHV3-XJ1), Botourmiaviridae sp.-XJ1 (BVsp-XJ1), and Fusariviridae sp.-XJ1 (Fvsp-XJ1) were new mycoviruses discovered within the Valsa spp. More importantly, compared with those in the virus-free Valsa spp. strain, the growth rate and virulence of the VN-5 strain co-infected with PlHV and CHV3-XJ1 were reduced by 59% and 75%, respectively, and the growth rate and virulence of the VN-34 strain infected with PlHV were reduced by 42% and 55%, respectively. On the other hand, the horizontal transmission efficiency of PlHV decreased when PlHV was co-infected with CHV3-XJ1, indicating that PlHV and CHV3-XJ1 were antagonistic. In summary, the mycoviruses in Valsa spp. were identified in Xinjiang for the first time, and three of them were newly discovered mycoviruses, with two strains yielding good results. These results will offer potential biocontrol resources for managing pear canker disease and provide a theoretical basis for the control of fruit tree Valsa canker disease.

The HIF1α polymorphism rs2301104 is associated with obesity and obesity-related cytokines in Han Chinese population.

AIMS: To evaluate the association between genetic polymorphisms of HIF1α and obesity and obesity-related cytokines in the Han Chinese population. METHODS: The study consisted of 160 subjects with obesity and 166 age- and gender-matched healthy controls. We genotyped three tag single nucleotide polymorphisms (SNPs) of HIF1α by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based genotyping technology. Plasma cytokine concentrations were determined on the Luminex platform. The genetic associations were analysed statistically. RESULTS: Obese subjects had significant obesity-related metabolic abnormalities, including hyperglycaemia, insulin resistance, and abnormalities in blood lipids, liver enzymes, and uric acid levels. SNP analysis of HIF1α revealed that the allele and genotype frequencies of rs2301104 were significantly associated with obesity. Our results suggest that the minor allele C of rs2301104 might be a protective mutation of obesity, and CC/CG genotypes of rs2301104 could be protective genotype of obesity. We also found that subjects with CC/CG genotypes of rs2301104 had significantly lower levels of IL-6, TNF-α, IL-1ß, IL-8, and IL-10 than subjects with GG genotypes. CONCLUSIONS: This is the first study to report an association between HIF1α polymorphisms and obesity and obesity-related cytokines in a Han Chinese population. These results require replication in larger populations but suggest that HIF1α may play an important role in obesity development.