高原鼢鼠干扰强度对祁连山东段高寒草甸大型土壤动物功能群特征及空间分布的影响

为明晰高原鼢鼠干扰对大型土壤动物类群分布和功能群特征影响,选取祁连山东段高原鼢鼠典型分布高寒草甸,依据鼠丘密度将研究区划分4个干扰梯度,调查各干扰区植物、群落结构、土壤理化性质和大型土壤动物功能群组成。采用冗余分析方法探讨植物土壤因子对土壤动物功能群组成和分布的影响。结果表明：研究区植食性土壤动物为优势功能群,极重度干扰区植食性功能群丰富度和Shannon多样性指数显著高于中度和重度干扰区(P<0.05);高原鼢鼠干扰对高寒草甸土壤动物群落稳定和相似性影响较小;冗余分析表明土壤温度、紧实度、全氮和全钾以及莎草科生物量和植物物种均匀度均显著影响高寒草甸土壤动物功能群的空间分布(P<0.05),其中土壤温度对土壤动物功能群分布影响最为显著。     

高原鼠兔干扰对高寒草甸植物多样性与土壤养分间关系的影响

高原鼠兔干扰虽然能够改变高寒草甸植物多样性与土壤养分含量,但植物多样性与土壤养分间的关系对高原鼠兔干扰的响应尚不清晰。利用高原鼠兔有效洞口密度将高原鼠兔干扰程度划分为T_1(7个/625 m~2)、T_2(12个/625 m~2)、T_3(22个/625m~2)、T_4(38个/625 m~2)4个水平,运用RDA冗余分析法研究了高原鼠兔不同干扰程度下高寒草甸植物多样性与土壤养分间的关系。结果表明:随着高原鼠兔干扰水平的增加,优势种高山嵩草(Kobresia pygmaea)的重要值先增加后降低,而伴生种小花草玉梅(Anemone rivularis var.flore-minors)和莓叶委陵菜(Potentilla fragarioides)的重要值先降低后增加;当高原鼠兔干扰水平从T_1到T_2时植物多样性指数变化不显著,而高原鼠兔干扰程度超过T_2时则植物多样性指数具有降低趋势;土壤全氮和硝态氮含量随高原鼠兔干扰水平增加而降低,而土壤铵态氮含量则降低后增加,土壤有机碳和全磷先增加后降低;多样性指数与0—10cm土壤深度硝态氮、10—20cm土壤深度全钾间的相关性从T_1到T_3时为正相关,而到T_4时则变为负相关,而与0—10cm土壤深度全氮的相关性则表现T_1到T_3时为负相关,T_4时为正相关,与铵态氮间相关性只有T_1时为负相关,这说明高原鼠兔干扰改变了植物多样性与土壤养分间的关系,其变化阈值介于T_2和T_3。     

高寒草甸不同扰动斑块植物功能群和根土复合体特征变化研究

高原鼠兔(Ochotona curzoniae)活动在高寒草甸上会形成各种类型扰动斑块, 扰动斑块类型的转变是导致草地退化的原因之一。目前, 斑块类型发生转变的关键影响因子尚不清楚, 因此, 对高寒草甸活动斑块、非活动斑块和恢复斑块三个扰动斑块类型植物功能类群结构、根土复合体特征和斑块分布特征进行研究, 旨在探讨斑块类型发生转变的主要因子, 说明高寒草甸退化机理。研究结果表明, 高寒草甸中活动斑块土壤表层由于放牧和高原鼠兔活动扰动强度大, 无法形成稳定的植物群落, 非活动斑块的植物群落处于次生演替早期阶段, 但是恢复斑块已具备高寒草甸优势种莎草科植物生长的基本条件。退化高寒草甸中活动斑块与非活动斑块呈现镶嵌性分布, 而恢复斑块相对独立没有镶嵌性分布现象。造成高寒草甸干扰斑块类型转变的主要原因是高原鼠兔活动强度由间歇性干扰转变为持续干扰的结果。     

放牧条件下高原鼠兔扰动对高寒草甸植物群落特征的影响

在高寒草甸生态系统中,大型草食动物放牧是重要的管理方式之一,对草地生物多样性起着关键的驱动作用。高原鼠兔是高寒草甸生态系统中生物多样性的重要组成成分,对生态系统的食物网结构以及其功能与稳定性起着关键作用。探明放牧条件下高原鼠兔扰动对高寒草甸的影响,对于高寒草甸建立合理的放牧提供理论依据,为鼠害的防治提供科学依据有一定的现实意义。2017年5—9月在青海省海北州祁连县矮嵩草草甸,以高原鼠兔为研究对象,通过小区控制研究放牧条件下高原鼠兔扰动对高寒草甸植物功能群植物特征的影响。结果显示高原鼠兔扰动降低了除杂类草以外的各植物功能群的高度;同时显著降低了禾本科、豆科功能群盖度及总盖度,而杂类草功能群的盖度有增加的趋势。另外,我们的结果也发现高原鼠兔扰动对各植物功能群生物量和重要值的影响不显著。该研究表明放牧条件下高原鼠兔扰动在一定程度上对杂草群落特征具有积极的作用,对其它功能群的群落特征具有抑制作用。     

高原鼠兔干扰对高寒草甸β多样性的影响

β多样性反映生物群落沿某一环境梯度的物种周转速率, 该研究尝试采用β多样性揭示植物群落随小型啮齿草食动物干扰梯度变化的生态过程。该研究利用野外随机样地的采集数据, 分析了高原鼠兔(Ochotona curzoniae)不同干扰强度下Whittaker指数的变化特征, 并利用群落二元丰富度的方差分解法, 确定了单个物种(SCBD)和单个干扰位点(LCBD)对β多样性的贡献。主要结果: 随高原鼠兔干扰强度增加, 植物群落内物种周转速率呈先增加后降低的趋势; 占据位点数居中的物种对区域内的β多样性贡献较大, 其中冰草(Agropyron cristatum)、臭蒿(Artemisia hedinii)、小花草玉梅(Anemone rivularis var. flore-minore)等单个物种对整个区域内β多样性的贡献最为突出; 整个区域内干扰位点T₀ (高原鼠兔干扰强度为0)对区域β多样性贡献值最大, LCBD值和该位点的群落丰富度呈显著负相关关系, 但与高原鼠兔干扰强度无显著关联。说明重点保护LCBD值高的干扰位点所在的高寒草甸, 以及SCBD值较高的冰草、臭蒿、小花草玉梅, 对保护高原鼠兔存在时高寒草甸植物群落多样性具有重要意义。     

高原鼠兔对高寒沼泽草甸土壤呼吸的干扰

高原鼠兔(Ochotona curzoniae)的穴居和啃食活动改变土壤养分含量、微生物群落、团聚体结构和孔隙度, 干扰生态系统土壤CO2排放, 对生态系统碳循环产生重要影响。为了研究高原鼠兔干扰下的高寒沼泽草甸土壤呼吸动态, 实验设计了高原鼠兔实验组和自然对照组, 采用LI-8100A土壤呼吸测量系统在2018年的生长季监测了高原鼠兔干扰下的土壤呼吸、土壤温度及土壤含水量, 分析了高原鼠兔对高寒沼泽草甸土壤呼吸的影响。实验发现: (1)在高原鼠兔活动干扰下土壤呼吸速率增加了9.58%(高原鼠兔实验组的土壤呼吸速率值为5.27 µmol·m-2·s-1, 自然对照组为5.22 µmol·m-2·s-1, P<0.05), (2)在高原鼠兔干扰下高寒沼泽草甸土壤呼吸对土壤温度的敏感程度(Q10)降低了21.02%; (3)土壤呼吸变化深受5 cm土壤温度变化的影响(P<0.05)。研究结果表明高原鼠兔活动深刻干扰高寒沼泽草甸土壤呼吸, 影响高寒沼泽草甸生态系统碳循环。因此, 在全球气候变暖的背景下, 加强高原鼠兔活动对高寒沼泽草甸土壤碳排放的干扰研究具有重要的科学与现实意义。     

高寒草甸鼠兔活动对土壤微生物群落特征的影响

高原鼠兔活动严重影响了高寒草甸生态系统的多样性及稳定性, 土壤微生物对环境变化高度敏感, 其群落特征受到了高原草甸鼠兔活动的显著影响。为探究鼠兔活动对土壤微生物群落结构及多样性的影响, 本实验以青海湖高寒草甸鼠兔活动干扰下的土壤微生物为研究对象, 基于细菌16s rRNA进行高通量测序。不同处理下的土壤细菌的优势菌群相似, 主要包括变形菌门和酸杆菌门。与自然状态下的高寒草甸相比, 鼠兔活动下的土壤细菌群落丰富度显著增加, 多样性指数显著降低 (P < 0.05)。鼠兔活动显著影响了土壤细菌的群落结构 (P < 0.05), 对照与鼠兔活动分组间存在104个差异菌群, 鼠兔活动下的亚表层土壤 (10—20 cm) 仅有3个菌群相对丰度显著升高, 鼠兔活动下的表层土壤 (0—10 cm) 则存在52个差异菌群。FAPROTAX预测分析表明, 土壤细菌群落功能基团多为碳氮代谢相关的功能基团, 另有部分与无氧呼吸途径及人类疾病有关。总体而言, 鼠兔活动显著影响了高寒草甸土壤细菌的群落结构及多样性特征, 且表层土壤的细菌群落对鼠兔活动的响应更为明显。     

高原鼠兔跑道对高寒草甸退化斑块扩大与连通的影响

高原鼠兔(Ochotona curzoniae)的活动会在退化高寒草甸草地上形成退化斑块,退化斑块的连通会导致高寒草甸破碎化,对高寒草甸完整性造成严重影响。本研究使用无人机拍摄不同刈割强度和鼠兔密度处理下高寒草甸图像,解译出退化斑块和高原鼠兔跑道。从地理信息系统中获得退化斑块面积信息,计算跑道连通性指数,识别高原鼠兔跑道在高寒草甸退化过程中的作用,确定高原鼠兔干扰活动对高寒草甸影响的临界条件。结果表明:高密度高原鼠兔处理的鼠兔跑道数显著增加(P0.05);退化斑块面积增量与连通性指数呈显著正相关(P0.05);高原鼠兔洞口数对鼠兔密度的处理不敏感(P0.05);随着退化斑块面积的增加,高原鼠兔洞口数显著减少(P0.05),高原鼠兔跑道连通性指数呈抛物线变化;高原鼠兔跑道是导致高寒草甸退化斑块扩大的原因之一,也会加速高寒草甸退化斑块的连通;当退化斑块面积达到临界值21%时,高寒草甸破碎化程度加剧。     

高原鼢鼠扰动及恢复年限对高寒草甸土壤养分和微生物功能多样性的影响

为了研究高原鼢鼠扰动后退化高寒草甸恢复演替的动态过程,利用常规实验室分析方法和Biolog-ECO生态板法对青藏高原东缘高寒草甸土壤养分和微生物功能多样性进行分析.结果表明: 高原鼢鼠扰动显著降低了土壤有机质、全氮、速效氮和速效磷含量,对土壤全磷和全钾含量无显著影响;在一定植被恢复年限内,土壤微生物的碳源利用率、Shannon、Pielou和McIntosh指数随着植被恢复年限的增加而升高;主成分分析表明,碳水化合物和氨基酸是土壤微生物利用的主要碳源类型;冗余分析表明,土壤pH、有机质、全氮、速效氮和全钾是影响土壤微生物代谢活性和功能多样性的主要因子.不同植被恢复年限土壤微生物功能多样性的变化可能是对地上植被、土壤微生物群落组成和土壤养分变化的响应.     

高原鼠兔对垂穗披碱草及豆科植物生长特性的影响

高原鼠兔通过取食对高寒草甸产生广泛的影响,从而影响高寒草甸植物的个体生长特征。2012年在青海省果洛州矮嵩草草甸,以高原鼠兔喜食植物(豆科和垂穗披碱草)为研究对象,通过小区控制研究高原鼠兔取食（对照组、低密度处理组、中密度处理组、高密度处理组）对植物个体生长特征的影响。研究显示：在实验前期（5月和6月）,喜食植物个体特征基本上无明显规律;在实验后期（7月和8月）,随着高原鼠兔取食强度增大,高原鼠兔喜食植物的地上生物量、平均高度、分蘖枝数、分蘖枝长度、丛幅均呈下降趋势;叶片长度和叶片数均呈先上升后下降态势。2.高原鼠兔喜食植物个体特征的增长率对照组显著高于高密度处理组（P<0.05）。以上结果表明(1)高寒草甸豆类植物在其生长后期与高原鼠兔的取食强度呈一定的负相关关系;高原鼠兔取食强度在阈值（中、低密度）内有利于垂穗披碱草的生长,但超过其阈值的取食强度不利于其生长。(2)高原鼠兔高强度的取食对其喜食植物个体的生长率有明显的抑制作用。     

高尿酸血症与肾脏疾病关系的研究进展

高尿酸血症(HUA)是血尿酸(UA)增高的一种疾病,也是常见的机体代谢紊乱,临床上大多数HUA患者无明显的症状。由于经济水平提高和生活方式的改变,其发病率有增高趋势,且男性高于女性。HUA多发于中老年人群,严重影响其生活质量,因此中老年人群HUA已经成为普遍关注的健康问题。近年来研究发现HUA是痛风的主要病因之一,并且血尿酸(UA)水平可导致肾功能减退。已有多项研究表明HUA与肾脏疾病的发生发展密切相关,HUA是Ig A肾病、糖尿病肾病、急性肾损伤等肾脏疾病的独立危险因素,本文主要从HUA的流行病学、危险因素、发病机制及其与肾脏疾病关系这几个方面展开综述。     

Hyperuricemia is independently associated with coronary heart disease and renal dysfunction in patients with type 2 diabetes mellitus

Aims

To investigate the relationship between hyperuricemia (HUA) and the clinical backgrounds in Japanese patients with type 2 diabetes mellitus.

Methods

After a cross-sectional study evaluating the association of HUA with the clinical characteristics in 1,213 patients with type 2 diabetes mellitus, the estimated glomerular filtration rate (eGFR) and the incidence of diabetic macroangiopathies was investigated in a prospective observational study in 1,073 patients during a 3.5 year period. HUA was defined by serum uric acid levels >327 μmol/L or as patients using allopurinol.

Results

The frequency of HUA was significantly higher in the diabetic patients (32% in men and 15% in women) than in the normal controls (14% in men and 1% in women). In total, HUA was found in 299 (25%) of the patients during the cross-sectional study. Even after adjusting for sex, drinking status, treatment for diabetes mellitus, body mass index, hypertension, use of diuretics, hyperlipidemia, HbA1c and/or the eGFR, the HUA was independently associated with some diabetic complications. The eGFR was significantly reduced in HUA patients compared to those with normouricemia in the 12 months after observation was started. HUA was also an independent risk factor for coronary heart disease even after adjustment in the Cox proportional hazard model.

Conclusions

HUA is a associated with diabetic micro- and macroangiopathies. HUA is a predictor of coronary heart disease and renal dysfunction in patients with type 2 diabetes mellitus. However, the influence of HUA is considered to be limited.     

High Uric Acid Induces Insulin Resistance in Cardiomyocytes In Vitro and In Vivo

Clinical studies have shown hyperuricemia strongly associated with insulin resistance as well as cardiovascular disease. Direct evidence of how high uric acid (HUA) affects insulin resistance in cardiomyocytes, but the pathological mechanism of HUA associated with cardiovascular disease remains to be clarified. We aimed to examine the effect of HUA on insulin sensitivity in cardiomyocytes and on insulin resistance in hyperuricemic mouse model. We exposed primary cardiomyocytes and a rat cardiomyocyte cell line, H9c2 cardiomyocytes, to HUA, then quantified glucose uptake with a fluorescent glucose analog, 2-NBDG, after insulin challenge and detected reactive oxygen species (ROS) production. Western blot analysis was used to examine the levels of insulin receptor (IR), phosphorylated insulin receptor substrate 1 (IRS1, Ser307) and phospho-Akt (Ser473). We monitored the impact of HUA on insulin resistance, insulin signaling and IR, phospho-IRS1 (Ser307) and phospho-Akt levels in myocardial tissue of an acute hyperuricemia mouse model established by potassium oxonate treatment. HUA inhibited insulin-induced glucose uptake in H9c2 and primary cardiomyocytes. It increased ROS production; pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger, reversed HUA-inhibited glucose uptake induced by insulin. HUA exposure directly increased the phospho-IRS1 (Ser307) response to insulin and inhibited that of phospho-Akt in H9C2 cardiomyocytes, which was blocked by NAC. Furthermore, the acute hyperuricemic mice model showed impaired glucose tolerance and insulin tolerance accompanied by increased phospho-IRS1 (Ser307) and inhibited phospho-Akt response to insulin in myocardial tissues. HUA inhibited insulin signaling and induced insulin resistance in cardiomyocytes in vitro and in vivo, which is a novel potential mechanism of hyperuricemic-related cardiovascular disease.     

New members of the floral organ identity AGAMOUS pathway

The Arabidopsis floral organ identity gene AGAMOUS (AG) specifies stamen and carpel development as well as floral determinacy. Recent reports suggest that the HUA1, HUA2, HEN1 and HEN2 genes function redundantly as components of the AG pathway. The HUA1, HUA2, HEN1 and HEN2 genes encode nuclear proteins that perhaps play a role in RNA metabolism. The HUA and HEN genes function not only on the AG pathway, but also in vegetative development.     

痛风与单纯性高尿酸血症人群高脂血症的对比分析

目的:对比分析痛风与单纯高尿酸血症合并高脂血症的情况。方法:收集青岛大学附属医院痛风专病门诊2009年5月至2016年1月收治的痛风患者7207例(男性6759例,女性448例),单纯高尿酸血症患者2095例(男性1852例,女性243例)。测量受试者身高、体重、腰围、臀围、血压、空腹血糖(FPG)、血甘油三酯(TG)、血胆固醇(TC)及血尿酸(UA),计算并比较两组高甘油三脂血症、高胆固醇血症的患病率,并分析其在痛风发生中的独立作用。结果:痛风组高甘油三酯血症和高胆固醇血症的患病率分别为57.8%、47.5%;单纯高尿酸血症组为51.8%、52.9%;两组率相比的比值比,高甘油三脂血症1.274[95%CI(1.155,1.404)],胆固醇血症0.805[95%CI(0.730,0.887)]。按性别分层分析,男性痛风组高甘油三脂血症、高胆固醇血症患病率分别为56.2%,46.8%;单纯高尿酸血症组分别为52.3%,52.6%。两组率相比的比值比,高甘油三脂血症1.25[95CI%(1.13,1.39)],高胆固醇血症0.80[95CI%(0.72,0.89)]。女性中痛风组高甘油三脂血症、高胆固醇血症患病率分别为52.2%,58.90%;单纯高尿酸血症组分别为46.6%,58.0%;两组差异无统计学意义。高甘油三脂血症与痛风的发生正相关OR=1.29,95%CI(1.12,1.48),高胆固醇血症与痛风的发生负相关OR=0.80,95%CI(0.73,0.89)。结论:痛风与单纯高尿酸血症患者存在不同的脂代谢状态,高甘油三酯血症可能是单纯高尿酸血症发展为痛风的危险因素。     

Two RNA binding proteins,HEN4 and HUA1, act in the processing of AGAMOUS pre-mRNA in Arabidopsis thaliana

AGAMOUS, a key player in floral morphogenesis, specifies reproductive organ identities and regulates the timely termination of stem cell fates in the floral meristem. Here, we report that strains carrying mutations in three genes, HUA1, HUA2, and HUA ENHANCER4 (HEN4), exhibit floral defects similar to those in agamous mutants: reproductive-to-perianth organ transformation and loss of floral determinacy. HEN4 codes for a K homology (KH) domain-containing, putative RNA binding protein that interacts with HUA1, a CCCH zinc finger RNA binding protein in the nucleus. We show that HUA1 binds AGAMOUS pre-mRNA in vitro and that HEN4, HUA1, and HUA2 act in floral morphogenesis by specifically promoting the processing of AGAMOUS pre-mRNA. Our studies underscore the importance of RNA processing in modulating plant development.     

Effects of HA-1077 and Y-27632, two rho-kinase inhibitors, in the human umbilical artery

A role for the small G protein rho and rho-kinase has been shown in smooth muscle contraction regarding Ca⁺⁺ sensitivity. However, there are no data in the literature assessing how this system operates in human umbilical arteries (HUA). Therefore, we evaluated the effects of HA-1077 and Y-27632, two rho-kinase inhibitors, on agonist-(5-hydroxytryptamine [5-HT]) and depolarization-induced (KCl) contractions of HUA. HA-1077 and Y-27632 inhibited 5-HT-induced contractile responses at 10⁻⁴ M concentration but not at 10⁻⁵ M. HA-1077 at 10⁻⁴ M also significantly attenuated contractions induced by 20 mM KCl. In addition, HUA precontracted with 5-HT relaxed concentration dependently in response to HA-1077 and Y-27632. When precontracted with KCl, HUA also relaxed dose-dependently in response to HA-1077, but the maximal relaxation was significantly smaller than the response obtained when precontracted with 5-HT. To determine possible involvement of rho-kinase on agonist-induced intracellular calcium-mediated contractions, tissues were precontracted with 5-HT in Ca⁺⁺-free Krebs solution before cumulative addition of HA-1077 or Y-27632 (10⁻⁷ to 10⁻⁴ M). Both rho-kinase inhibitors relaxed HUA completely. Maximum relaxations of HUA to HA-1077 and Y-27632 were significantly larger than the responses seen in normal Krebs solution and were obtained with lower concentrations of the drugs considered to be more specific for rho-kinase inhibition. However, preincubation of HUA with HA-1077 or Y-27632 (10⁻⁵ M for both) did not affect the 5-HT-induced contractions in this medium. Finally, immunoblot experiments revealed the expression of rho-kinase isoform rockII protein in HUA. These results indicate that rhoA/rho-kinase pathway can contribute to agonist-induced contractions of HUA. However, this effect appears to be limited to intracellular calcium-induced contractions and may be more important in sustaining contractions rather than the initial phase of force development.     

Prediction model of random forest for the risk of hyperuricemia in a Chinese basic health checkup test

Objectives: The present study aimed to develop a random forest (RF) based prediction model for hyperuricemia (HUA) and compare its performance with the conventional logistic regression (LR) model. Methods: This cross-sectional study recruited 91,690 participants (14,032 with HUA, 77,658 without HUA). We constructed a RF-based prediction model in the training sets and evaluated it in the validation sets. Performance of the RF model was compared with the LR model by receiver operating characteristic (ROC) curve analysis. Results: The sensitivity and specificity of the RF models were 0.702 and 0.650 in males, 0.767 and 0.721 in females. The positive predictive value (PPV) and negative predictive value (NPV) were 0.372 and 0.881 in males, 0.159 and 0.978 in females. AUC of the RF models was 0.739 (0.728–0.750) in males and 0.818 (0.799–0.837) in females. AUC of the LR models were 0.730 (0.718–0.741) for males and 0.815 (0.795–0.835) for females. The predictive power of RF was slightly higher than that of LR, but was not statistically significant in females (Delong tests, P=0.0015 for males, P=0.5415 for females). Conclusion: Compared with LR, the good performance in HUA status prediction and the tolerance of features associations or interactions showed great potential of RF in further application. A prospective cohort is necessary for HUA developing prediction. People with high risk factors should be encouraged to actively control to reduce the probability of developing HUA.     

High uric acid directly inhibits insulin signalling and induces insulin resistance

Background and aim

Accumulating clinical evidence suggests that hyperuricemia is strongly associated with abnormal glucose metabolism and insulin resistance. However, how high uric acid (HUA) level causes insulin resistance remains unclear. We aimed to determine the direct role of HUA in insulin resistance in vitro and in vivo in mice.

Methods

An acute hyperuricemia mouse model was created by potassium oxonate treatment, and the impact of HUA level on insulin resistance was investigated by glucose tolerance test, insulin tolerance test and insulin signalling, including phosphorylation of insulin receptor substrate 1 (IRS1) and Akt. HepG2 cells were exposed to HUA treatment and N-acetylcysteine (NAC), reactive oxygen species scavenger; IRS1 and Akt phosphorylation was detected by Western blot analysis after insulin treatment.

Results

Hyperuricemic mice showed impaired glucose tolerance with insulin resistance. Hyperuricemia inhibited phospho-Akt (Ser473) response to insulin and increased phosphor-IRS1 (Ser307) in liver, muscle and fat tissues. HUA induced oxidative stress, and the antioxidant NAC blocked HUA-induced IRS1 activation and Akt inhibition in HepG2 cells.

Conclusion

This study supplies the first evidence of HUA directly inducing insulin resistance in vivo and in vitro. Increased uric acid level may inhibit IRS1 and Akt insulin signalling and induce insulin resistance. The reactive oxygen species pathway plays a key role in HUA-induced insulin resistance.