BACKGROUND & AIMS: Our aim was to determine the effects of 12 h of hypoxaemia on cerebral blood flow (CBF) and cerebral O2 delivery in ovine fetuses at 0.6 gestation. During fetal hypoxaemia, induced by reduced uterine blood flow, fetal SaO2 and PaO2 were reduced (p < 0.01) from control values of 77.0 +/- 1.6% and 27.3 +/- 1.0 mm Hg, respectively, to 28.4 +/- 3.4% and 15.6 +/- 0.6 mm Hg; fetal pHa decreased from control values of 7.37 +/- 0.01 to 7.20 +/- 0.02 at 3 h, but returned to control values before 12 h. CBF (ml/min/100 g) was 2.0- to 2.6-fold higher (p < 0.01) than control values during hypoxaemia, but only 1.7-fold higher (p < 0.01) at 3 h when pHa was lowest. Cerebral O2 delivery (ml/min/100 g) was lower (p < 0.01) than control values of 3.15 +/- 0.29 at 1.5h (2.09 +/- 0.36) and 3h (1.84 +/- 0.22) of hypoxaemia and higher 1 h after hypoxaemia had ceased (3.81 +/- 0.22, p < 0.01). We conclude that the ovine fetus at 0.6 gestation is unable to sustain increased CBF and hence maintain cerebral O2 delivery during the first 6 h of hypoxaemia, a time which coincides with acidaemia; in contrast, at 6 and 12 h of hypoxaemia, when pHa was normal, cerebral O2 delivery was similar to control values. Reduced cerebral O2 delivery during the early, acidaemic, stages of hypoxaemia may lead to impaired neural development.

背景与目标： 我们的目的是确定12小时低氧血症对0.6妊娠的绵羊胎儿脑血流量 (CBF) 和脑O2输送的影响。在胎儿低氧血症期间，由子宫血流量减少引起的胎儿SaO2和PaO2从77.0 +/- 1.6% 和27.3 +/-1.0毫米Hg的对照值分别降低到28.4 +/- 3.4% 和15.6 +/-0.6毫米Hg (p <0.01); 胎儿pHa在3小时从7.37 +/- 0.01的对照值降至7.20 +/- 0.02，但在12小时前恢复到对照值。在低氧血症期间，CBF (ml/min/100g) 比对照值高2.0至2.6倍 (p <0.01)，但在3小时pHa最低时仅高1.7倍 (p <0.01)。低氧血症1.5小时 (2.09 +/- 0.36) 和3小时 (1.84 +/- 0.22) 时，脑O2递送 (ml/min/100g) 低于3.15 +/- 0.29的对照值 (p <0.01)，低氧血症停止后1小时更高 (3.81 +/- 0.22，p <0.01)。我们得出的结论是，0.6妊娠的绵羊胎儿无法维持CBF的增加，因此在低氧血症的前6小时 (与酸血症相吻合) 中维持脑O2的输送; 相反，在低氧血症的6和12小时，当pHa正常时，脑O2输送与对照值相似。低氧血症的早期，酸血症阶段的脑O2输送减少可能导致神经发育受损。

BACKGROUND & AIMS: :Purpose of this study was to assess the additional value of first pass myocardial perfusion imaging during peak dose of dobutamine stress Cardiac-MR (CMR). Dobutamine Stress CMR was performed in 115 patients with an inconclusive diagnosis of myocardial ischemia on a 1.5 T system (Magnetom Avanto, Siemens Medical Systems). Three short-axis cine and grid series were acquired during rest and at increasing doses of dobutamine (maximum 40 microg/kg/min). On peak dose dobutamine followed immediately by a first pass myocardial perfusion imaging sequence. Images were graded according to the sixteen-segment model, on a four point scale. Ninety-seven patients showed no New (Induced) Wall Motion Abnormalities (NWMA). Perfusion imaging showed absence of perfusion deficits in 67 of these patients (69%). Perfusion deficits attributable to known previous myocardial infarction were found in 30 patients (31%). Eighteen patients had NWMA, indicative for myocardial ischemia, of which 14 (78%) could be confirmed by a corresponding perfusion deficit. Four patients (22%) with NWMA did not have perfusion deficits. In these four patients NWMA were caused by a Left Bundle Branch Block (LBBB). They were free from cardiac events during the follow-up period (median 13.5 months; range 6-20). Addition of first-pass myocardial perfusion imaging during peak-dose dobutamine stress CMR can help to decide whether a NWMA is caused by myocardial ischemia or is due to an (inducible) LBBB, hereby preventing a false positive wall motion interpretation.

背景与目标： : 这项研究的目的是评估多巴酚丁胺应激心脏MR (CMR) 峰值剂量期间首过心肌灌注成像的附加价值。多巴酚丁胺应激CMR在1.5 T系统 (Magnetom Avanto，Siemens Medical Systems) 上对115例未明确诊断为心肌缺血的患者进行。在休息期间和增加多巴酚丁胺的剂量 (最大40微克/千克/分钟) 获得了三个短轴电影和网格系列。在峰值剂量多巴酚丁胺之后立即进行首过心肌灌注成像序列。根据十六段模型对图像进行了四分制的分级。97名患者未显示新的 (诱发的) 壁运动异常 (NWMA)。灌注成像显示这些患者中有67例 (69%) 不存在灌注缺陷。在30例患者 (31%) 中发现了可归因于已知先前心肌梗塞的灌注缺陷。18例患者患有NWMA，指示心肌缺血，其中14例 (78% 例) 可以通过相应的灌注不足来确认。四名NWMA患者 (22%) 没有灌注缺陷。在这四名患者中，NWMA是由左束支传导阻滞 (LBBB) 引起的。在随访期间 (中位13.5个月; 范围6-20)，他们没有心脏事件。在峰值剂量多巴酚丁胺应激CMR期间增加首过心肌灌注成像可以帮助确定NWMA是由心肌缺血引起还是由 (可诱导的) LBBB引起，从而防止假阳性壁运动解释。

BACKGROUND & AIMS: :The effects of ionisation density on the structure of the glow curve of LiF:Mg,Ti (TLD-100) are briefly reviewed and discussed within the framework of the spatially correlated TC/LC model and localised recombination. The effects of 'slow-cooling' on the structure of composite peak 5 following low-ionisation density beta/gamma irradiation are described and analysed in both 'slow-cooled' and 'normally cooled' samples. It is demonstrated that 'slow-cooling' using a cooling rate of 30 degrees C h(-1) increases the relative intensity of glow peak 5a to composite glow peak 5 from approximately 0.1 to approximately 2, thereby greatly improving the precision of measurement of the ratio 5a/5. The improved precision removes a hurdle impeding the development of the ionisation density discrimination properties of the peak 5a/5 nanodosimeter.

背景与目标： : 在空间相关的TC/LC模型和局部重组的框架内，简要回顾和讨论了电离密度对LiF:Mg，Ti (TLD-100) 辉光曲线结构的影响。在 “慢冷” 和 “正常冷却” 样品中描述并分析了低电离密度 β/γ 辐照后 “慢冷” 对复合峰5结构的影响。证明了使用30 °c h(-1) 的冷却速率的 “缓慢冷却” 将辉光峰5a与复合辉光峰5的相对强度从大约0.1增加到大约2，从而大大提高了比率5a/5的测量精度。提高的精度消除了阻碍峰5a/5纳米剂量计电离密度判别特性发展的障碍。

BACKGROUND & AIMS: :The evolution of oxygen transport hemoglobins occurred on at least two independent occasions. The earliest event led to myoglobin and red blood cell hemoglobin in animals. In plants, oxygen transport "leghemoglobins" evolved much more recently. In both events, pentacoordinate heme sites capable of inert oxygen transfer evolved from hexacoordinate hemoglobins that have unrelated functions. High sequence homology between hexacoordinate and pentacoordinate hemoglobins in plants has poised them for potential structural analysis leading to a molecular understanding of this important evolutionary event. However, the lack of a plant hexacoordinate hemoglobin structure in the exogenously ligand-bound form has prevented such comparison. Here we report the crystal structure of the cyanide-bound hexacoordinate hemoglobin from barley. This presents the first opportunity to examine conformational changes in plant hexacoordinate hemoglobins upon exogenous ligand binding, and reveals structural mechanisms for stabilizing the high-energy pentacoordinate heme conformation critical to the evolution of reversible oxygen binding hemoglobins.

背景与目标： : 氧转运血红蛋白的演变至少发生在两个独立的场合。最早的事件导致动物出现肌红蛋白和红细胞血红蛋白。在植物中，氧气运输 “leghe血红蛋白” 是最近进化的。在这两种情况下，能够惰性氧转移的五配位的血红素位点都是由具有无关功能的六配位的血红蛋白进化而来的。植物中六配位和五配位血红蛋白之间的高序列同源性使它们可以进行潜在的结构分析，从而对这一重要的进化事件有了分子理解。然而，由于缺乏外源配体结合形式的植物六配位血红蛋白结构，因此无法进行这种比较。在这里，我们报告了大麦中氰化物结合的六配位血红蛋白的晶体结构。这为研究外源配体结合后植物六配位血红蛋白的构象变化提供了第一个机会，并揭示了稳定对可逆氧结合血红蛋白的进化至关重要的高能五配位血红素构象的结构机制。

BACKGROUND & AIMS: BACKGROUND:The reasons for low adherence to cereal dietary guidelines are not well understood but may be related to knowledge, attitudes, beliefs and perceived barriers. This study aims to assess trends in cereal foods consumption, intention to change and factors associated with intake among Western Australian (WA) adults 18 to 64 years. METHOD:Cross-sectional data from the 1995, 1998, 2001, 2004, 2009, and 2012 Nutrition Monitoring Survey Series involving 7044 adults were pooled. OUTCOME VARIABLES:types and amount of cereals (bread, rice, pasta, and breakfast cereal) eaten the day prior. Attitudes, knowledge, intentions, weight status and sociodemographic characteristics were measured. Descriptive statistics, multiple binary logistic and multinomial logistic regressions assess factors associated with consumption. RESULTS:Bread (78%) was the most commonly consumed cereal food. The proportion eating bread decreased across survey years (Odds Ratio OR = 0.31; 95% Confidence Interval; 0.24-0.40 in 2012 versus 1995), as did the amount (4.1 slices of bread in 1995 to 2.4 in 2012). The odds of consuming whole-grain cereal foods increased since 2009 (OR = 1.27; 1.02-1.58 versus 1995 p < 0.05). The likelihood of trying to eat less cereal food in the past year was greater in 2012 compared to 1995 (Relative Risk Ratio RRR 10.88; 6.81-17.4). Knowledge of cereal recommendations decreased over time (OR = 0.20; 0.15-0.27 in 2012 versus 1995 p < 0.001). Overweight and obese respondents were more likely than healthy weight respondents to have tried to eat less cereals (RRR 1.65; 1.22-2.24 and 1.88; 1.35-2.63 respectively). 'I already eat enough' was the main barrier (75% in 1995 to 84% in 2012 (p < 0.001)). CONCLUSIONS:WA adults are actively reducing the amount of cereal foods they eat and intake is associated with a misperception of adequacy of intake. Nutrition intervention is needed to increase awareness of the health benefits of cereal foods, particularly whole-grains, and to address barriers to incorporating them daily. TRIAL REGISTRATION:Not applicable.

背景与目标：

BACKGROUND & AIMS: :Oxygen therapy can be life-saving for patients with chronic obstructive pulmonary disease (COPD) and is the backbone of any acute COPD treatment strategy. Although largely considered to be a benign drug, many publications have highlighted the need to accurately adjust oxygen delivery to avoid both hypoxemia and the problem of hyperoxia-induced hypercapnia. Recent clinical data have shown that the deleterious effects of excess oxygen treatment can not only alter carbon dioxide levels (which has been known for more than 60 years) but can also lead to an increase in mortality. Nevertheless, despite the extensive literature, the risks associated with hyperoxia are often overlooked and published clinical recommendations are largely ignored. This failure in knowledge translation has become increasingly important not only because of the desire to reduce medical error, but in a society with limited health care resources, the economic burden of COPD is such that it cannot afford to make preventable medical mistakes. Recently, novel devices have been developed to automatically adjust oxygen flow rates to maintain stable oxygen saturations. These closed-loop oxygen delivery systems have the potential to reduce medical error, improve morbidity and mortality, and reduce health care costs. Preliminary data in this field are promising and will require a significant amount of research in the coming years to determine the precise indications for these systems. The importance of appropriate oxygen dosing and the current literature regarding novel oxygen delivery systems are reviewed.

背景与目标： : 氧疗可以挽救慢性阻塞性肺疾病 (COPD) 患者的生命，并且是任何急性COPD治疗策略的支柱。尽管在很大程度上被认为是一种良性药物，但许多出版物都强调需要准确调整氧气输送以避免低氧血症和高氧诱导的高碳酸血症的问题。最近的临床数据表明，过量氧气治疗的有害影响不仅会改变二氧化碳水平 (已知已有60多年的历史)，还会导致死亡率增加。然而，尽管有大量文献，但与高氧相关的风险经常被忽视，发表的临床建议在很大程度上被忽视。这种知识翻译的失败变得越来越重要，这不仅是因为希望减少医疗错误，而且在医疗资源有限的社会中，COPD的经济负担使它无法承受可预防的医疗错误。最近，已经开发了新颖的设备来自动调节氧气流速以保持稳定的氧气饱和度。这些闭环氧气输送系统具有减少医疗错误，提高发病率和死亡率以及降低医疗保健成本的潜力。该领域的初步数据很有希望，并且在未来几年中将需要大量研究以确定这些系统的确切指示。回顾了适当的氧气剂量的重要性以及有关新型氧气输送系统的当前文献。

BACKGROUND & AIMS: :Catalysing the reduction of oxygen in acidic media is a standing challenge. Although activity of platinum, the most active metal, can be substantially improved by alloying, alloy stability remains a concern. Here we report that platinum nanoparticles supported on graphite-rich boron carbide show a 50-100% increase in activity in acidic media and improved cycle stability compared to commercial carbon supported platinum nanoparticles. Transmission electron microscopy and x-ray absorption fine structure analysis confirm similar platinum nanoparticle shapes, sizes, lattice parameters, and cluster packing on both supports, while x-ray photoelectron and absorption spectroscopy demonstrate a change in electronic structure. This shows that purely electronic metal-support interactions can significantly improve oxygen reduction activity without inducing shape, alloying or strain effects and without compromising stability. Optimizing the electronic interaction between the catalyst and support is, therefore, a promising approach for advanced electrocatalysts where optimizing the catalytic nanoparticles themselves is constrained by other concerns.

背景与目标： : 催化酸性介质中氧的还原是一个长期的挑战。尽管通过合金化可以大大提高铂 (最具活性的金属) 的活性，但合金的稳定性仍然令人担忧。在这里，我们报告，与商业碳负载的铂纳米颗粒相比，负载在富含石墨的碳化硼上的铂纳米颗粒在酸性介质中显示出50-100% 的活性增加和改进的循环稳定性。透射电子显微镜和x射线吸收精细结构分析证实了两种载体上相似的铂纳米颗粒形状，大小，晶格参数和团簇堆积，而x射线光电子和吸收光谱表明电子结构发生了变化。这表明，纯电子金属-载体相互作用可以显着提高氧还原活性，而不会引起形状，合金化或应变效应，并且不会损害稳定性。因此，优化催化剂和载体之间的电子相互作用是先进的电催化剂的一种有前途的方法，其中优化催化纳米颗粒本身受到其他问题的限制。

BACKGROUND & AIMS: OBJECTIVE:The present study examined whether ethanol exposure influences lactation parameters. Specifically, selected constituents in maternal blood and milk and the lactation performance of Chinese lactating mothers were evaluated after they had consumed chicken soup flavoured with sesame oil and rice wine (CSSR), a diet traditionally prescribed during the postpartum 'doing-the-month' ritual. DESIGN:Twenty-three lactating mothers were examined. Informed consent was obtained from each subject. Each subject was tested on two occasions separated by a week. The target alcohol dosage was 0.3 g/kg body weight. Milk and blood samples were collected prior to consumption of soup and at 120 and 150 min, respectively, after consumption. Levels of various constituents were measured. The time for ejection of the first milk droplet and total milk volume yielded were also measured. RESULTS:Consumption of CSSR influenced TAG, insulin and lactate levels in maternal blood. Likewise, consumption of the soup affected milk composition and its nutritional status, particularly total protein, TAG, fatty acid, beta-hydroxybutyrate and lactate levels. CSSR intake significantly affected TAG and lactate levels in milk. The time for the first milk droplet to be ejected was significantly longer in the CSSR group, indicating that the milk-ejecting reflex is inhibited. However, blood prolactin level increased slightly after ethanol intake. Milk yields were reduced after ingestion of CSSR although the difference was not statistically significant. CONCLUSION:Consumption of CSSR affects not only the composition of maternal blood and milk, but also lactation performance. These findings suggest that an alcoholic diet should be avoided during lactation.

背景与目标：

BACKGROUND & AIMS: :In this study, oxygen and nitrate regulation of transcription and subsequent protein expression of the unique narK1K2GHJI respiratory operon of Pseudomonas aeruginosa were investigated. Under the control of PLAC, P. aeruginosa was able to transcribe nar and subsequently express methyl viologen-linked nitrate reductase activity under aerobic conditions without nitrate. Modulation of PLAC through the LacI repressor enabled us to assess both transcriptional and posttranslational regulation by oxygen during physiological whole-cell nitrate reduction.

背景与目标： : 在这项研究中，研究了铜绿假单胞菌独特的narK1K2GHJI呼吸操纵子的氧和硝酸盐对转录的调节以及随后的蛋白表达。在PLAC的控制下，铜绿假单胞菌能够转录nar，随后在有氧条件下无硝酸盐的情况下表达甲基紫精连接的硝酸还原酶活性。通过LacI阻遏物对PLAC的调节使我们能够评估生理全细胞硝酸盐还原过程中氧气的转录和翻译后调节。

BACKGROUND & AIMS: :Epidemiological studies indicate that diets rich in fruits and vegetables (F&V) are protective against CVD. Puréed F&V products retain many beneficial components, including flavonoids, carotenoids, vitamin C and dietary fibres. The present study aimed to establish the physiological effects of acute ingestion of a F&V purée-based drink (FVPD) on vasodilation, antioxidant status, phytochemical bioavailability and other CVD risk factors. A total of twenty-four subjects, aged 30-70 years, completed the randomised, single-blind, controlled, crossover test meal study. Subjects consumed 400 ml of the FVPD, or a fruit-flavoured sugar-matched control, after following a low-flavonoid diet for 5 d. Blood and urine samples were collected throughout the study day, and vascular reactivity was assessed at 90 min intervals using laser Doppler iontophoresis. The FVPD significantly increased plasma vitamin C (P= 0·002) and total nitrate/nitrite (P= 0·001) concentrations. There was a near significant time by treatment effect on ex vivo LDL oxidation (P= 0·068), with a longer lag phase after consuming the FVPD. During the 6 h after juice consumption, the antioxidant capacity of plasma increased significantly (P= 0·003) and there was a simultaneous increase in plasma and urinary phenolic metabolites (P< 0·05). There were significantly lower glucose and insulin peaks after ingestion of the FVPD compared with control (P= 0·019 and 0·003) and a trend towards increased endothelium-dependent vasodilation following FVPD consumption (P= 0·061). Overall, FVPD consumption significantly increased plasma vitamin C and total nitrate/nitrite concentrations, with a trend towards increased endothelium-dependent vasodilation. Puréed F&V products are useful vehicles for increasing micronutrient status, plasma antioxidant capacity and in vivo NO generation, which may contribute to CVD risk reduction.

背景与目标： 流行病学研究表明，富含水果和蔬菜 (F & V) 的饮食对心血管疾病有保护作用。纯净的F & V产品保留了许多有益的成分，包括类黄酮，类胡萝卜素，维生素c和膳食纤维。本研究旨在确定急性摄入F & V浓汤饮料 (FVPD) 对血管舒张，抗氧化状态，植物化学生物利用度和其他CVD危险因素的生理影响。共有24名年龄在30-70岁之间的受试者完成了随机，单盲，对照，交叉测试餐研究。在低类黄酮饮食5天后，受试者食用了400毫升FVPD或水果味糖匹配对照。在整个研究日收集血液和尿液样本，并使用激光多普勒离子电渗疗法以90分钟的间隔评估血管反应性。FVPD显着增加血浆维生素c (P = 0·002) 和总硝酸盐/亚硝酸盐 (P = 0·001) 的浓度。离体LDL氧化的治疗效果几乎有显着的时间 (P = 0·068)，消耗FVPD后的滞后阶段更长。在榨汁后6 h，血浆抗氧化能力显着增加 (P = 0·003)，血浆和尿中酚类代谢产物同时增加 (P< 0·05)。与对照组相比，摄入FVPD后葡萄糖和胰岛素峰值显着降低 (P = 0·019和0·003)，并且在消耗FVPD后内皮依赖性血管舒张趋势增加 (P = 0·061)。总体而言，FVPD的摄入显着增加了血浆维生素c和总硝酸盐/亚硝酸盐浓度，并有增加内皮依赖性血管舒张的趋势。纯净的F & V产品是增加微量营养素状态，血浆抗氧化能力和体内NO生成的有用载体，这可能有助于降低CVD风险。

BACKGROUND & AIMS: :Emerging evidence indicates that reactive oxygen species, especially superoxide and hydrogen peroxide, are important signaling molecules in cardiovascular cells. Their production is regulated by hormone-sensitive enzymes such as the vascular NAD(P)H oxidases, and their metabolism is coordinated by antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Both of these reactive oxygen species serve as second messengers to activate multiple intracellular proteins and enzymes, including the epidermal growth factor receptor, c-Src, p38 mitogen-activated protein kinase, Ras, and Akt/protein kinase B. Activation of these signaling cascades and redox-sensitive transcription factors leads to induction of many genes with important functional roles in the physiology and pathophysiology of vascular cells. Thus, reactive oxygen species participate in vascular smooth muscle cell growth and migration; modulation of endothelial function, including endothelium-dependent relaxation and expression of a proinflammatory phenotype; and modification of the extracellular matrix. All of these events play important roles in vascular diseases such as hypertension and atherosclerosis, suggesting that the sources of reactive oxygen species and the signaling pathways that they modify may represent important therapeutic targets.

背景与目标： : 新兴证据表明，活性氧，尤其是超氧化物和过氧化氢，是心血管细胞中的重要信号分子。它们的产生受激素敏感酶 (例如血管NAD(P)H氧化酶) 调节，其代谢受抗氧化酶 (例如超氧化物歧化酶，过氧化氢酶和谷胱甘肽过氧化物酶) 协调。这两种活性氧都是激活多种细胞内蛋白质和酶的第二信使，包括表皮生长因子受体c-Src，p38丝裂原激活的蛋白激酶，Ras和Akt/蛋白激酶B。这些信号级联和氧化还原敏感的转录因子的激活导致诱导许多在血管细胞的生理和病理生理中具有重要功能作用的基因。因此，活性氧参与血管平滑肌细胞的生长和迁移; 调节内皮功能，包括内皮依赖性舒张和促炎表型的表达; 和细胞外基质的修饰。所有这些事件在诸如高血压和动脉粥样硬化等血管疾病中起着重要作用，表明活性氧的来源及其修饰的信号通路可能是重要的治疗靶点。

BACKGROUND & AIMS: BACKGROUND:Limited evidence suggests that calcium intake before puberty influences adolescent height growth and the timing of puberty. Such an effect might be particularly marked in populations in whom low calcium intake, stunting, and delayed puberty are common. OBJECTIVE:The objective was to test whether 12 mo of calcium supplementation at age 8-12 y to increase intakes toward international recommendations had long-term effects on adolescent growth and pubertal development in rural Gambian children. DESIGN:This was a longitudinal study of 160 Gambian boys (n = 80) and girls (n = 80) who had participated in a 12-mo, randomized, double-blind, placebo-controlled, calcium carbonate supplementation trial (1000 mg Ca/d, 5 d/wk) at age 8-12 y. Anthropometric measures were made every 1-2 y until age 21-25 y; pubertal status and menarche data were collected. Repeated-measures ANCOVA and Superimposition by Translation and Rotation Method (SITAR) growth models were used to assess the effects of treatment. RESULTS:In boys, midadolescent height growth was advanced in the calcium group, which resulted in greater stature at a mean age of 15.5 y (mean ± SEM: 2.0 ± 0.8 cm; P = 0.01) and an earlier age of peak height velocity by 7.4 ± 2.9 mo. Subsequently, the calcium group stopped growing earlier (P = 0.02) and was 3.5 ± 1.1 cm shorter (P = 0.002) at a mean age of 23.5 y. Weight and midupper arm circumference paralleled height. No significant effects were observed in girls, but a sex-by-supplement interaction on height growth could not be confirmed. CONCLUSION:Calcium supplementation of boys in late childhood advanced the age of peak height velocity and resulted in shorter adult stature in a population in whom low calcium intakes and delayed puberty are common. This trial was registered at isrctn.org as ISRCTN28836000.

背景与目标：

BACKGROUND & AIMS: PURPOSE:This review aims to compare the magnitude of the effects of chronic consumption of fruits; specifically berries, citrus and cherries on cardiovascular disease (CVD) risk factors. METHODS:PubMed, Web of Science, Scopus, and psycARTICLES were searched from inception until January 2020. Forty-five chronic (≥ 1 week) randomised controlled trials assessing CVD risk factors including endothelial (dys)function, blood pressure (BP), blood lipids and inflammatory biomarkers were included. RESULTS:Investigated interventions reported improvements in endothelial function (n = 8), inflammatory biomarkers and lipid status (n = 14), and BP (n = 10). Berries including juice of barberry, cranberry, grape, pomegranate, powder of blueberry, grape, raspberry and freeze-dried strawberry significantly reduced SBP by 3.68 mmHg (95% CI - 6.79 to - 0.58; P = 0.02) and DBP by 1.52 mmHg (95% CI - 2.87 to - 0.18, P = 0.04). In subgroup analysis, these associations were limited to cranberry juice (SBP by 1.52 mmHg [95% CI - 2.97 to - 0.07; P = 0.05], DBP by 1.78 mmHg [95% CI - 3.43 to - 0.12, P = 0.04] and cherry juice (SBP by 3.11 mmHg [95% CI - 4.06 to - 2.15; P = 0.02]). Berries also significantly elevated sVCAM-1 levels by 14.57 ng/mL (85% CI 4.22 to 24.93; P = 0.02). CONCLUSION:These findings suggest that supplementing cranberry or cherry juice might contribute to an improvement in blood pressure. No other significant improvements were observed for other specified fruits. More research is warranted comparing different classes of fruit and exploring the importance of fruit processing on their cardiovascular-protective effects.

背景与目标：

BACKGROUND & AIMS: :Speleothem oxygen isotope records over East Asia reveal apparently large and rapid paleoclimate changes over the last several hundred thousand years. However, what the isotopic variation actually represent in terms of the regional climate and circulation is debated. We present an answer that emerges from an analysis of the interannual variation in amount-weighted annual δ18O of precipitation over East Asia as simulated by an isotope-enabled model constrained by large-scale atmospheric reanalysis fields. 18O-enriched years have reduced summer seasonality both in terms of precipitation isotopes and in the large-scale circulation. Changes occur between June and October, where the δ18O of precipitation (δ18Op) transitions from the isotopically heavier winter to the lighter summer regime. For 18O-enriched years, this transition is less pronounced. Variations in precipitation amount alone are insufficient to explain the amount-weighted annual δ18Op between 18O-enriched and 18O-depleted years. Reduced summer seasonality is also expressed in the low-level monsoonal southerlies and upper-level westerlies; for the latter, the northward migration across the Tibetan Plateau in the summer is less pronounced. Our result thus implicates the westerlies across the plateau as the proximate cause of East Asian paleomonsoon changes, manifested as a modulation of its summer peak.

背景与目标： : 东亚地区的speleo他们的氧同位素记录显示，在过去的几十万年中，古气候变化明显而迅速。然而，就区域气候和环流而言，同位素变化实际上代表了什么。我们提出了一个答案，该答案是通过对受大规模大气再分析场约束的同位素启用模型模拟的东亚地区降水量加权年 δ18O的年际变化进行分析得出的。18o年丰富的年份在降水同位素和大规模环流方面都降低了夏季的季节性。6月和10月之间发生变化，降水的 δ18O (δ18Op) 从同位素较重的冬季过渡到较轻的夏季。对于18o年丰富的年份，这种转变不太明显。仅降水量的变化不足以解释18o年富集和18o年枯竭之间的加权年 δ18Op。降低的夏季季节性也表现在低层的季风南部和上层的西风中; 对于后者，夏季穿越青藏高原的北移不太明显。因此，我们的结果暗示整个高原的西风是东亚古月变化的直接原因，表现为其夏季高峰的调制。

BACKGROUND & AIMS: :The hypoxia-inducible factor 1alpha (HIF-1alpha) is the master regulator of the cellular response to hypoxia. A key regulator of HIF-1alpha is von Hippel-Lindau protein (pVHL), which mediates the oxygen-dependent, proteasomal degradation of HIF-1alpha in normoxia. Here, we describe a new regulator of HIF-1alpha, the hypoxia-associated factor (HAF), a novel E3-ubiquitin ligase that binds HIF-1alpha leading to its proteasome-dependent degradation irrespective of cellular oxygen tension. HAF, a protein expressed in proliferating cells, binds and ubiquitinates HIF-1alpha in vitro, and both binding and E3 ligase activity are mediated by HAF amino acids 654 to 800. Furthermore, HAF overexpression decreases HIF-1alpha levels in normoxia and hypoxia in both pVHL-competent and -deficient cells, whereas HAF knockdown increases HIF-1alpha levels in normoxia, hypoxia, and under epidermal growth factor stimulation. In contrast, HIF-2alpha is not regulated by HAF. In vivo, tumor xenografts from cells overexpressing HAF show decreased levels of HIF-1alpha accompanied by decreased tumor growth and angiogenesis. Therefore, HAF is the key mediator of a new HIF-1alpha-specific degradation pathway that degrades HIF-1alpha through a new, oxygen-independent mechanism.

背景与目标： : 缺氧诱导因子1α (HIF-1alpha) 是细胞对缺氧反应的主要调节剂。HIF-1alpha的关键调节剂是von Hippel-Lindau蛋白 (pVHL)，它介导常氧中HIF-1alpha的氧依赖性蛋白酶体降解。在这里，我们描述了一种新的HIF-1alpha调节剂，即缺氧相关因子 (HAF)，这是一种新型的E3-ubiquitin连接酶，可结合HIF-1alpha导致其蛋白酶体依赖性降解，而与细胞氧张力无关。HAF是一种在增殖细胞中表达的蛋白质，在体外结合并HIF-1alpha泛素化，并且结合和E3连接酶活性均由654 800的HAF氨基酸介导。此外，HAF过表达降低了pVHL感受态和缺陷型细胞中常氧和缺氧的HIF-1alpha水平，而HAF敲低则增加了常氧，缺氧和表皮生长因子刺激下的HIF-1alpha水平。相反，HIF-2alpha不受HAF的调节。在体内，来自过表达HAF的细胞的肿瘤异种移植物显示出降低的HIF-1alpha水平，伴随着降低的肿瘤生长和血管生成。因此，HAF是一种新的HIF-1alpha-specific降解途径的关键介质，该途径通过一种新的不依赖氧的机制降解HIF-1alpha。