BACKGROUND & AIMS: :Iron is an essential trace-element for most organisms. However, because high concentration of free intracellular iron is cytotoxic, cells have developed complex regulatory networks that keep free intracellular iron concentration at optimal range, allowing the incorporation of the metal into iron-using enzymes and minimizing damage to the cell. We built a mathematical model of the network that controls iron uptake and usage in the bacterium Escherichia coli to explore the dynamics of iron flow. We simulate the effect of sudden decrease or increase in the extracellular iron level on intracellular iron distribution. Based on the results of simulations we discuss the possible roles of the small RNA RyhB and the Fe-S cluster assembly systems in the optimal redistribution of iron flows. We suggest that Fe-S cluster assembly is crucial to prevent the accumulation of toxic levels of free intracellular iron when the environment suddenly becomes iron rich.

背景与目标： 铁是大多数生物必不可少的微量元素。但是，由于高浓度的游离细胞内铁具有细胞毒性，因此细胞已开发出复杂的调节网络，可将游离细胞内铁的浓度保持在最佳范围，从而将金属掺入使用铁的酶中，并将对细胞的损害降至最低。我们建立了控制该细菌大肠杆菌中铁的吸收和使用的网络数学模型，以探索铁流量的动态变化。我们模拟了细胞外铁水平突然降低或增加对细胞内铁分布的影响。基于模拟的结果，我们讨论了小RNA RyhB和Fe-S簇组装系统在铁流的最佳重新分配中的可能作用。我们建议，当环境突然变得富含铁时，Fe-S簇组装对于防止游离细胞内铁的毒性水平的积累至关重要。

BACKGROUND & AIMS: :The band alignment at an Al2O3/SrTiO3 heterointerface forming a two-dimensional electron gas (2DEG) was investigated using scanning photocurrent microscopy (SPCM) in an electrolyte-gated environment. We used a focused UV laser source for above-the-bandgap illumination on the SrTiO3 layer, creating electron-hole pairs that contributed to the photocurrent through migration towards the metal electrodes. The polarity of the SPCM signals of a bare SrTiO3 device shows typical p-type behavior at zero gate bias, in which the photogenerated electrons are collected by the electrodes. In contrast, the SPCM polarity of 2DEG device indicates that the hole carriers were collected by the metal electrodes. Careful transport measurements revealed that the gate-dependent conductance of the 2DEG devices exhibits n-type switching behavior. More importantly, the SPCM signals in 2DEG devices demonstrated very unique gate-responses that cannot be found in conventional semiconducting devices, based on which we were able to perform detailed investigation into the electronic band alignment of the 2DEG devices and obtain the valence band offset at the heterointerface.

背景与目标： ：使用扫描光电流显微镜（SPCM）在电解质门控环境中研究了形成二维电子气（2DEG）的Al2O3 / SrTiO3异质界面处的能带排列。我们使用聚焦的UV激光源在SrTiO3层上进行带隙以上照明，从而创建电子-空穴对，这些电子-空穴对通过向金属电极的迁移而有助于光电流。裸露的SrTiO3器件的SPCM信号的极性在零栅极偏置下显示出典型的p型行为，其中光生电子被电极收集。相反，2DEG器件的SPCM极性表明空穴载流子被金属电极收集。仔细的传输测量表明，2DEG器件的依赖于栅极的电导表现出n型开关行为。更重要的是，2DEG设备中的SPCM信号表现出非常独特的门响应，这是常规半导体设备中无法找到的，基于此，我们能够对2DEG设备的电子能带对准进行详细研究，并获得价带偏移。异类接口。

BACKGROUND & AIMS: :The effect of ascorbic acid on iron retention from a diet with predicted low iron bioavailability (containing minimal meat and ascorbic acid) was investigated in iron-depleted premenopausal women. Eleven women were depleted of storage iron (indicated by serum ferritin) through a combination of diet (5.0 mg Fe/2000 kcal for 67-88 d) and phlebotomy. They then consumed a diet containing 13.7 mg Fe/2000 kcal, supplemented with placebo or ascorbic acid three times daily (1500 mg total) with meals for 5.5 wk. Ascorbic acid improved apparent iron absorption (balance method) [38 +/- 2% (means +/- SEM) vs 27 +/- 2%]. Ascorbic acid also improved hemoglobin, erythrocyte protoporphyrins, and serum iron but not hematocrit, serum ferritin, iron-binding capacity, or transferrin saturation. In iron-depleted women consuming a diet with predicted poor iron availability, ascorbic acid supplementation enhanced body iron retention for 5.5 wk.

背景与目标： ：在缺铁的绝经前妇女中研究了抗坏血酸对铁的生物滞留量具有预期低铁含量（含少量肉和抗坏血酸）的饮食中铁保留的影响。通过饮食（5.0 mg Fe / 2000 kcal，67-88 d）和静脉放血相结合，耗尽了11名妇女的铁储备（以血清铁蛋白表示）。然后，他们进食了含有13.7 mg Fe / 2000 kcal的饮食，每天补充3次（共1500 mg）安慰剂或抗坏血酸，并进餐5.5周。抗坏血酸提高了表观铁的吸收（平衡法）[38 /-2％（平均值/-SEM）对27 /-2％]。抗坏血酸还可以改善血红蛋白，红血球原卟啉和血清铁，但不能改善血细胞比容，血清铁蛋白，铁结合能力或转铁蛋白饱和度。在饮食中铁含量低的女性中，铁的可利用性预计较差，补充抗坏血酸可增加体内铁保持5.5周的能力。

BACKGROUND & AIMS: :The cause-effect relationship between iron deficiency anemia (IDA) and osteoporosis has not been established in the general population. Thus, the current longitudinal study determined the role of IDA as a risk factor for osteoporosis by analyzing a large nationwide population-based sample. In a sample of 1,000,000 randomly sampled individuals from the 1998-2012. Taiwan National Health Insurance Research Database, patients with IDA (case group (n = 35,751)) and individuals without IDA (control group (n = 178,755)) were compared. Patients who were <20 years of age and who had pre-existing osteoporosis prior to the diagnosis of IDA were excluded. Each patient with IDA was age- and gender-matched to five individuals without IDA. The diagnoses of IDA and osteoporosis (coded using ICD-9CM) were further confirmed with blood test results and X-ray bone densitometry to ensure the accuracy of the diagnoses. Osteoporosis occurred more often among patients with IDA compared to individuals without IDA (2.27% vs. 1.32%, p < 0.001). Cox proportional hazard analysis revealed that the risk for osteoporosis was significantly higher in the case than the control group (hazard ratio (HR) = 1.74; 95% CI = 1.61-1.88) and remained similar after adjustment for covariates (adjusted HR = 1.81; 95% CI = 1.67-1.97). Compared with individuals without IDA, the risk for osteoporosis was even higher for patients with IDA who received intravenous ferrum therapy (adjusted HR = 2.21; 95% CI = 1.85-2.63). In contrast, the risk for osteoporosis was reduced for patients with IDA who received a blood transfusion (adjusted HR = 1.47; 95% CI = 1.20-1.80). As a predictor, prior IDA is a significant and independent risk factor for development of osteoporosis.

背景与目标： ：铁缺乏性贫血（IDA）和骨质疏松症之间的因果关系尚未建立。因此，当前的纵向研究通过分析全国范围内大量的基于人群的样本，确定了IDA作为骨质疏松症危险因素的作用。在1998年至2012年的1,000,000个随机样本中进行抽样。台湾国家健康保险研究数据库比较了IDA患者（病例组（n = 35,751））和无IDA患者（对照组（n = 178,755））。年龄小于20岁且在IDA诊断之前已存在骨质疏松症的患者被排除在外。每名IDA患者的年龄和性别均与五名没有IDA的患者相匹配。通过血液测试结果和X射线骨密度测定进一步证实了IDA和骨质疏松的诊断（使用ICD-9CM编码），以确保诊断的准确性。与没有IDA的患者相比，IDA患者的骨质疏松症发生率更高（2.27％对1.32％，p <0.001）。 Cox比例风险分析显示，骨质疏松症的风险明显高于对照组（风险比（HR）= 1.74； 95％CI = 1.61-1.88），并且在调整协变量后（调整后HR = 1.81； 95％CI = 1.67-1.97）。与没有IDA的个体相比，接受静脉铁素治疗的IDA患骨质疏松症的风险更高（校正后的HR = 2.21； 95％CI = 1.85-2.63）。相反，接受输血的IDA患者的骨质疏松风险降低（校正后的HR = 1.47； 95％CI = 1.20-1.80）。作为预测因素，先前的IDA是骨质疏松症发展的重要且独立的危险因素。

BACKGROUND & AIMS: :Cellular iron homeostasis is maintained by iron and heme transport proteins that work in concert with ferrireductases, ferroxidases, and chaperones to direct the movement of iron into, within, and out of cells. Systemic iron homeostasis is regulated by the liver-derived peptide hormone, hepcidin. The interface between cellular and systemic iron homeostasis is readily observed in the highly dynamic iron handling of four main cell types: duodenal enterocytes, erythrocyte precursors, macrophages, and hepatocytes. This review provides an overview of how these cell types handle iron, highlighting how iron and heme transporters mediate the exchange and distribution of body iron in health and disease.

背景与目标： ：铁和血红素转运蛋白与铁还原酶，铁氧化酶和伴侣蛋白协同作用，维持细胞内铁稳态，从而指导铁进入，进入和离开细胞的运动。系统性铁稳态由肝脏衍生的肽激素hepcidin调节。在铁的四种主要细胞类型的高动态铁处理中，很容易观察到细胞与全身铁稳态之间的界面：十二指肠肠上皮细胞，红细胞前体，巨噬细胞和肝细胞。这篇综述概述了这些细胞类型如何处理铁，着重介绍了铁和血红素转运蛋白如何在健康和疾病中介导体内铁的交换和分布。

BACKGROUND & AIMS: :Iron deficiency and fatigue are common problems in adolescent females. Heavy menstrual bleeding (HMB) is associated with both iron deficiency and fatigue. The aim of this study was to define baseline ferritin values and fatigue symptoms in a population of young females with excessive menstrual blood loss, as compared to healthy controls. The study population included 11 to 17-year-old menstruating females presenting to an Adolescent Gynaecology Clinic, Menorrhagia Clinic or Sports Medicine clinic. To evaluate the degree and effects of menstrual blood loss, we utilized the Ruta Menorrhagia Severity Score. We investigated the symptoms of fatigue using the Fatigue Severity Scale. We evaluated possible predictors of ferritin level (age, body mass index, fatigue scores and Menorrhagia Severity Score) using generalized linear models. A total of 48 adolescents with HMB and 102 healthy adolescents completed the study. Iron deficiency and elevated fatigue scores were common findings in young women with HMB. Both fatigue severity scores and menorrhagia severity scores were significantly higher in young women with HMB as compared to healthy controls. In adolescents with HMB, 87.5% had ferritin levels ≤40 ng mL(-1), and 29.2% had ferritin levels ≤15 ng mL(-1). Our generalized linear models did not identify any significant univariate relationships between ferritin levels and patient age, body mass index, fatigue score or menorrhagia score. Iron deficiency and symptoms of fatigue are common findings in young women with HMB. Fatigue severity scores are significantly higher in young women with HMB as compared to healthy controls.

背景与目标： ：铁缺乏和疲劳是青春期女性的常见问题。严重的月经出血（HMB）与铁缺乏和疲劳有关。这项研究的目的是确定与健康对照组相比，月经失血过多的年轻女性人群的基线铁蛋白值和疲劳症状。研究人群包括就诊于青春期妇科诊所，月经过多诊所或运动医学诊所的11至17岁的月经女性。为了评估月经失血的程度和影响，我们使用了Ruta Menorrhagia严重度评分。我们使用疲劳严重程度量表调查了疲劳症状。我们使用广义线性模型评估了铁蛋白水平的可能预测因子（年龄，体重指数，疲劳评分和月经过多程度）。共有48名HMB青少年和102名健康青少年完成了这项研究。缺铁和疲劳评分升高是HMB年轻女性的常见发现。与健康对照组相比，HMB年轻女性的疲劳严重程度评分和月经过多严重程度评分均显着更高。在HMB青少年中，铁蛋白水平≤40 ng mL（-1）占87.5％，铁蛋白水平≤15 ng mL（-1）占29.2％。我们的广义线性模型未发现铁蛋白水平与患者年龄，体重指数，疲劳评分或月经过多评分之间存在任何显着的单变量关系。铁缺乏症和疲劳症状是HMB年轻女性的常见发现。与健康对照组相比，HMB年轻女性的疲劳严重程度评分明显更高。

BACKGROUND & AIMS: :Ongoing blood loss and iron-deficiency anemia are common problems in patients on hemodialysis; therefore, nephrology clinicians are particularly concerned with their patients who are scheduled for surgery Surgery can cause significant blood and iron losses, thereby worsening their preexisting anemia. However, patients on hemodialysis can be effectively treated preoperatively by adjusting their continued doses of intravenous (i.v.) iron and recombinant human erythropoietin (EPO) therapy, based on expected blood and iron losses. This valuable strategy can help improve surgical and anemia outcomes as well as decrease EPO requirements and the need for transfusions. This article examines the use of IV iron and EPO therapy as preventive therapy for anemia in patients on hemodialysis prior to invasive surgical procedures, illustrated with an experience from a dialysis unit and patient case studies.

背景与目标： ：持续的失血和缺铁性贫血是血液透析患者的常见问题；因此，肾脏病临床医生特别关心计划进行手术的患者。手术可能会导致大量的血液和铁丢失，从而加剧他们先前的贫血。但是，根据预期的血液和铁的流失，通过调整静脉注射铁和重组人促红细胞生成素（EPO）治疗的持续剂量，可以对接受血液透析的患者进行术前有效治疗。这种有价值的策略可以帮助改善手术和贫血结果，并降低EPO需求和输血需求。本文探讨了在进行侵入性外科手术之前，静脉输注铁和EPO疗法作为血液透析患者贫血的预防性疗法的应用，并结合透析部门和患者案例研究的经验进行了说明。

BACKGROUND & AIMS: OBJECTIVE:To evaluate the outcomes of and barriers to implementing standard guidelines (Caring for Australasians with renal impairment [CARI]), using iron management in patients having dialysis as an example. DESIGN AND SETTING:On-site review of iron management processes at six Australian dialysis units varying in size and locality. Patients' iron indices and haemoglobin levels were obtained from the Australian and New Zealand Dialysis and Transplant Registry. PARTICIPANTS:Patients with chronic kidney disease who were dependent on dialysis. MAIN OUTCOME MEASURES:Processes for assessing indices of iron stores and iron supplementation; comparison with target indices in the CARI guidelines. RESULTS:There was considerable variability among the units in achievement of haemoglobin and iron targets, with 25%-32% of patients achieving haemoglobin targets of 110-120 g/L, 30%-68% achieving ferritin targets of 300-800 microg/L, and 65%-73% achieving transferrin saturation targets of 20%-50%. Implementation barriers included lack of knowledge, lack of awareness of or trust in the CARI guideline, inability to implement the guideline, and inability to agree on a uniform unit protocol. Factors associated with achieving the CARI guideline targets included nurse-driven iron management protocols, use of an iron management decision aid, fewer nephrologists per dialysis unit, and a "proactive" (actively keeping iron levels within target range) rather than "reactive" (only reacting if iron levels are out of the range) protocol. CONCLUSIONS:Variability in achievement of iron targets, despite the availability of a clinical practice guideline, may be explained by variability in processes of care for achieving and maintaining adequate iron parameters.

背景与目标： 目的：以透析患者的铁管理为例，评估标准指南（护理患有肾功能不全的澳大利亚人[CARI]）的结果和障碍。
设计与设置：对六个澳大利亚透析单位的铁管理流程进行现场审查，这些单位的大小和位置各不相同。患者的铁指数和血红蛋白水平从澳大利亚和新西兰透析与移植注册处获得。
对象：依赖于透析的慢性肾脏病患者。
主要观察指标：储铁量和补铁指标评估过程；与CARI指南中的目标指标进行比较。
结果：各单位在实现血红蛋白和铁目标方面存在很大差异，其中25％-32％的患者达到110-120 g / L的血红蛋白目标，30％-68％的患者达到300-800 microg /的铁蛋白目标L和65％-73％达到20％-50％的转铁蛋白饱和度目标。实施障碍包括缺乏知识，缺乏对CARI准则的认识或信任，无法实施该准则以及无法就统一的单位协议达成共识。与实现CARI指导方针目标相关的因素包括护士驱动的铁管理方案，铁管理决策辅助工具的使用，每个透析部门的肾脏病医生较少以及“主动”（将铁水平保持在目标范围内）而非“反应性”（仅在铁含量超出范围时反应）。
结论：尽管有临床实践指南，实现铁靶的可变性仍可以通过达到和维持适当铁参数的护理过程中的可变性来解释。

BACKGROUND & AIMS: AIM:To determine whether concomitant iron affects the absorption of mycophenolate mofetil. METHODS:An open-label, single centre, randomized, crossover trial was conducted in 16 healthy males. Fasting subjects received mycophenolate mofetil alone (treatment A) or co-administered with iron (treatment B). RESULTS:The mycophenolic acid AUC(0,24 h) for treatments A and B were 42.5 +/- 10.5 and 44.7 +/- 12.4 microg ml(-1) h, respectively. anova modelling showed the relative bioavailability of mycophenolate mofetil to be similar for the two treatments (90% confidence interval 0.92, 1.19). CONCLUSIONS:There was no interaction between mycophenolate mofetil and iron supplements administered concomitantly to healthy fasting subjects.

背景与目标： 目的：确定伴随的铁是否影响霉酚酸酯的吸收。
方法：对16名健康男性进行了开放标签，单中心，随机，交叉试验。空腹受试者单独接受霉酚酸酯（治疗A）或与铁合用（治疗B）。
结果：处理A和B的霉酚酸AUC（0,24 h）分别为42.5 /-10.5和44.7 /-12.4 microg ml（-1）h。方差分析建模显示，两种处理的霉酚酸酯的相对生物利用度相似（90％置信区间为0.92、1.19）。
结论：麦考酚酸酯与健康禁食对象同时服用铁补充剂之间没有相互作用。

BACKGROUND & AIMS: Histochemical, immunohistochemical, and biochemical evidence is reported showing that the ink gland of the cuttlefish Sepia officinalis contains a calcium-dependent isoform of nitric oxide synthase as well as an NMDA R1 receptor subunit localized for the most part in the immature inner cells of the epithelial layer of the gland. These results may be taken to implicate a hitherto unrecognized regulatory role of the glutamate-nitric oxide pathway in the maturation and metabolic activity of melanin-producing cells in the cephalopod defense system.

背景与目标： 据组织化学，免疫组化和生物化学证据显示，墨鱼乌贼墨the的墨腺含有一氧化氮合酶的钙依赖性同种型，以及大部分位于上皮未成熟内细胞中的NMDA R1受体亚基。腺体层。这些结果可能暗示了迄今为止尚未认识到的谷氨酸一氧化氮途径在头足防御系统中黑色素生成细胞的成熟和代谢活性中的作用。

BACKGROUND & AIMS: :Infused CD34 cell count has a significant impact on transplant outcome. In this retrospective study, we aimed to analyze the impact of donor iron parameters on peripheral blood stem cell (PBSC) collection. A total of 303 related donors were included in the study. The mobilization regimen, recombinant G-CSF, was given for four consecutive days. A CD34+ cell count below 2×106/kg was defined as mobilization failure which was demonstrated in 23 donors (7.6%). Mobilization failure was more frequent in female donors than male donors (13.7% vs 3.4%). Body mass index, mean corpuscular volume, hemoglobin and ferritin levels were found to be lower in donors with mobilization failure. Body mass index was significantly correlated with PBSC count on the 4th day of G-CSF. Body mass index, male gender, mean corpuscular volume and ferritin levels had significant impact on PBSC count. Although PBSC count was found to be similar between female and male donors, female gender was shown to have an adverse impact on PBSC collection, which may be attributed to lower body weight and concurrent iron deficiency.

背景与目标： ：注入的CD34细胞数量对移植结果有重要影响。在这项回顾性研究中，我们旨在分析供体铁参数对外周血干细胞（PBSC）收集的影响。总共303名相关捐助者被纳入研究。连续四天给予了动员方案，即重组G-CSF。低于2×106 / kg的CD34细胞计数被定义为动员失败，这在23个捐献者（7.6％）中得到证实。女性捐赠者的动员失败率比男性捐赠者更高（13.7％vs 3.4％）。发现动员失败的献血者的体重指数，平均红细胞体积，血红蛋白和铁蛋白水平较低。体重指数与G-CSF第4天的PBSC计数显着相关。体重指数，男性，平均红细胞体积和铁蛋白水平对PBSC计数有显着影响。尽管发现雌性和雄性供体之间的PBSC计数相似，但显示出性别对PBSC收集有不利影响，这可能归因于体重减轻和同时发生的铁缺乏症。

BACKGROUND & AIMS: :Urease, a nickel-containing metalloenzyme, was the first enzyme to be crystallized and has a prominent position in the history of biochemistry. In the present study, we identified a nickel urease gene cluster, ureABCEFGDH, in Bacillus paralicheniformis ATCC 9945a and characterized it in Escherichia coli Enzymatic assays demonstrate that this oxygen-stable urease is also an iron-containing acid urease. Heterologous expression assays of UreH suggest that this accessory protein is involved in the transmembrane transportation of nickel and iron ions. Moreover, this iron-containing acid urease has a potential application in the degradation of urea in rice wine. The present study not only enhances our understanding of the mechanism of activation of urease but also provides insight into the evolution of metalloenzymes.IMPORTANCE An iron-containing, oxygen-stable acid urease from B. paralicheniformis ATCC 9945a with good enzymatic properties was characterized. This acid urease shows activities toward both urea and ethyl carbamate. After digestion with 6 U/ml urease, approximately 92% of the urea in rice wine was removed, suggesting that this urease has great potential in the food industry.

背景与目标： ：脲酶，一种含镍的金属酶，是第一个被结晶的酶，在生物化学史上占有重要地位。在本研究中，我们在副芽孢杆菌ATCC 9945a中鉴定了镍脲酶基因簇ureABCEFGDH，并在大肠杆菌中对其进行了表征。酶法测定表明，该氧稳定脲酶也是一种含铁的酸性脲酶。 UreH​​的异源表达测定表明该辅助蛋白与镍和铁离子的跨膜运输有关。此外，这种含铁的酸性脲酶在米酒中尿素的降解中具有潜在的应用。本研究不仅增进了我们对脲酶激活机理的理解，而且为金属酶的发展提供了见识。重要特征表征了副枝芽孢杆菌ATCC 9945a具有良好的酶学性质的含铁，氧稳定的酸性脲酶。该酸性脲酶显示出对脲和氨基甲酸乙酯的活性。用6 U / ml尿素酶消化后，黄酒中约有92％的尿素被去除，这表明该尿素酶在食品工业中具有巨大的潜力。

BACKGROUND & AIMS: :Data are presented indicating that the growth of 5 out of 5 murine lymphoid tumors can be inhibited in a synergistic fashion in vitro by combined treatment with the iron chelator deferoxamine (DFO) and an immunoglobulin G (IgG) monoclonal anti-transferrin receptor antibody (ATRA). A two-way dose/response analysis shows that the ATRA becomes more efficient as an inhibitor with increasing doses of DFO. Flow cytometric studies further support the view that IgG ATRAS impair transferrin receptor (TR) function by causing TR down-modulation and degradation, even when the presence of DFO acts to promote increased cell surface TR expression. It is also shown that an IgG ATRA is nearly as effective as an IgM ATRA in inhibiting tumor cell growth when used in combination with DFO. Finally, studies with the iron chelator picolinic acid show that it produces only additive, or very slightly supra-additive, effects when used in combination with the ATRA. Therefore, these studies not only continue to suggest that combination chelator/ATRA therapy warrants further investigation as a tool in the therapy of hematopoietic malignancies, but also make the following new points: (1) the clinically familiar iron chelator deferoxamine, but not all iron chelators, produces synergistic inhibition of tumor growth in vitro with ATRAS; and (2) IgG ATRAS, which may be clinically more attractive reagents than IgA or IgM ATRAS because of better access to extra vascular tissue spaces, have unexpectedly been found to function as powerful growth inhibitors when used in combination with DFO.

背景与目标： ：数据表明，通过与铁螯合剂去铁胺（DFO）和免疫球蛋白G（IgG）单克隆抗转铁蛋白受体抗体联合治疗，可以在体外以协同方式抑制5种鼠类淋巴瘤中5种的生长。 ATRA）。双向剂量/响应分析表明，随着DFO剂量的增加，ATRA作为抑制剂的效率更高。流式细胞术研究进一步支持这样一种观点，即即使存在DFO时，IgG ATRAS也会通过引起TR下调和降解而损害运铁蛋白受体（TR）的功能，即使DFO的存在会促进细胞表面TR表达的增加。还显示了当与DFO组合使用时，IgG ATRA在抑制肿瘤细胞生长方面几乎与IgM ATRA一样有效。最后，对铁螯合剂吡啶甲酸的研究表明，当与ATRA结合使用时，它仅产生加成或极轻微的超加成作用。因此，这些研究不仅继续表明，螯合剂/ ATRA组合疗法作为造血系统恶性肿瘤治疗的工具值得进一步研究，而且还提出了以下新观点：（1）临床上熟悉的铁螯合剂去铁胺，但并非所有铁螯合剂，在体外与ATRAS产生协同抑制肿瘤生长的作用； （2）IgG ATRAS在临床上可能比IgA或IgM ATRAS具有更强的吸引力，因为它可以更好地进入多余的血管组织空间，与DFO组合使用时，出乎意料地起到了强大的生长抑制剂的作用。

BACKGROUND & AIMS: :The diffusible messenger, nitric oxide plays multiple roles in neuroprotection, neurodegeneration and brain plasticity. Its involvement in neurogenesis has been disputed, on the basis of results on models in vivo and in culture. We report here that pharmacological blockade of nitric oxide production in rat pups resulted, during a restricted time window of the first three postnatal days, in increased cerebellar proliferation rate, as assessed through tritiated thymidine or BrdU incorporation into DNA. This was accompanied by increased expression of Myc, a transcription factor essential for cerebellar development, and of the cell cycle regulating gene, cyclin D1. These effects were mediated downstream by the nitric oxide-dependent second messenger, cGMP. Schedules of pharmacological NO deprivation targeted to later developmental stages (from postnatal day 3 to 7), no longer increased proliferation, probably because of partial escape of the cGMP level from nitric oxide control. Though limited to a brief temporal window, the proliferative effect of neonatal nitric oxide deprivation could be traced into adulthood. Indeed, the number of BrdU-labeled surviving cells, most of which were of neuronal phenotype, was larger in the cerebellum of 60-day-old rats that had been subjected to NO deprivation during the first three postnatal days than in control rats. Experiments on cell cultures from neonatal cerebellum confirmed that nitric oxide deprivation stimulated proliferation of cerebellar precursor cells and that this effect was not additive with the proliferative action of sonic hedgehog peptide. The finding that nitric oxide deprivation during early cerebellar neurogenesis, stimulates a brief increase in cell proliferation may contribute to a better understanding of the controversial role of nitric oxide in brain development.

背景与目标： ：弥散性信使，一氧化氮在神经保护，神经变性和脑可塑性中起多种作用。根据体内和培养模型的结果，它在神经发生中的作用一直存在争议。我们在这里报告说，通过natal化胸腺嘧啶脱氧核苷或BrdU掺入DNA评估，在大鼠出生后前三天的有限时间窗内，在大鼠幼崽中产生一氧化氮的药理学阻断作用导致小脑增殖率的提高。这伴随着Myc和小细胞周期调节基因cyclin D1的表达增加，Myc是小脑发育所必需的转录因子。这些效应是由依赖一氧化氮的第二信使cGMP介导的。针对发育后期（从出生后第3天到第7天）的药理性NO剥夺时间表不再增加增殖，这可能是因为cGMP水平从一氧化氮控制中部分逃逸了。尽管仅限于短暂的时间窗，但新生儿一氧化氮剥夺的增殖作用可追溯至成年期。实际上，在出生后前三天被NO剥夺的60日龄大鼠小脑中，BrdU标记的存活细胞的数量多于对照大鼠，其中大多数为神经元表型。新生儿小脑细胞培养的实验证实，一氧化氮的缺乏会刺激小脑前体细胞的增殖，并且这种作用不会与声波刺猬肽的增殖作用相加。小脑早期神经发生过程中一氧化氮的缺乏会刺激细胞增殖的短暂增加，这一发现可能有助于更好地理解一氧化氮在脑发育中的作用。

BACKGROUND & AIMS: :We investigate the effects of detergent on the kinetics and oligomeric state of allene oxide synthase (AOS) from Arabidopsis thaliana (CYP74A1). We show that detergent-free CYP74A1 is monomeric and highly water soluble with dual specificity, but has relatively low activity. Detergent micelles promote a 48-fold increase in k(cat)/K(m) (to 5.9 x 10(7)M(-1)s(-1)) with concomitant changes in the spin state equilibrium of the haem-iron due to the binding of a single detergent micelle to the protein monomer, which is atypical of P450 enzymes. This mechanism is shown to be an important determinant of the substrate specificity of CYP74A1. CYP74A1 may be suited for structural resolution of the first plant cytochrome P450 and its 9-AOS activity and behaviour in vitro has implications for its role in planta.

背景与目标： ：我们研究了洗涤剂对拟南芥（CYP74A1）的氧化烯合酶（AOS）动力学和低聚状态的影响。我们显示不含洗涤剂的CYP74A1是单体的，具有双特异性的高度水溶性，但活性相对较低。洗涤剂微团促进k（cat）/ K（m）增加48倍（至5.9 x 10（7）M（-1）s（-1）），同时血红素铁的自旋态平衡发生变化由于单个去污剂胶束与蛋白质单体结合，这是非典型的P450酶。已显示该机制是CYP74A1底物特异性的重要决定因素。 CYP74A1可能适合第一种植物细胞色素P450的结构解析，其9-AOS活性和体外行为对其在植物中的作用具有影响。