BACKGROUND & AIMS: :In Escherichia coli at least five enzyme activities required for the beta-oxidation of fatty acids are associated with a multienzyme complex composed of two subunits in alpha 2 beta 2 conformation (A. Pramanik et al., J. Bacteriol. 137:469-473, 1979). In the present work, the DNA sequence of the genes encoding these two subunits, fadB and fadA, has been determined. The direction of transcription was from fadB to fadA rather than from fadA to fadB, as suggested previously (S. K. Spratt et al., J. Bacteriol. 158:535-542, 1984). Only 10 nucleotides separated the coding sequences for the two peptides, confirming the suggestion that these genes form an operon. The peptides encoded by fadB and fadA were 729 amino acids and 387 amino acids, respectively, in length. The larger and smaller peptides had predicted molecular masses of 79,678 and 40,876 Da, respectively. Recently, the sequence of the fadA gene was published in a separate report (Yang et al., J. Biol. Chem. 265:10424-10429, 1990). In this work, most of the DNA sequence for fadA was confirmed, and 10 errors were corrected. Three of these nucleotide changes resulted in five amino acid residue changes predicted in the carboxy terminus of the fadA-encoded peptide. By comparison to other peptide sequences, the alpha subunit encoded within fadB had 31% perfect identity with the rat peroxisomal enoyl-coenzyme A:hydratase-3-hydroxyacyl-coenzyme A dehydrogenase trifunctional enzyme over the entire length of the two peptides. In agreement with the work of Yang et al., the beta subunit encoded within fadA had 35 to 45% perfect identity with five thiolase genes from different eucaryotic sources over the entire length of the peptide.

背景与目标： 在大肠杆菌中，脂肪酸的 β-氧化所需的至少五种酶活性与由 α2β2构象中的两个亚基组成的多酶复合物相关 (a.Pramanik等人，J. Bacteriol. 137:469-473，1979)。在本工作中，已经确定了编码这两个亚基fadB和fadA的基因的DNA序列。转录的方向是从fadB到fadA，而不是从fadA到fadB，如前所述 (S. K. Spratt等人，J. Bacteriol. 158:535-542，1984)。只有10个核苷酸分离了两个肽的编码序列，证实了这些基因形成操纵子的暗示。fadB和fadA编码的肽长度分别为729个氨基酸和387个氨基酸。较大和较小的肽分别预测79,678和40,876 Da的分子量。最近，fadA基因的序列发表在单独的报告中 (Yang等人，J. Biol. Chem. 265:10424-10429，1990)。在这项工作中，fadA的大部分DNA序列得到了确认，并纠正了10个错误。这些核苷酸变化中的三个导致fadA编码肽的羧基末端预测的五个氨基酸残基变化。与其他肽序列相比，fadB内编码的 α 亚基与大鼠过氧化物酶体烯酰辅酶a具有31% 完美的同一性: 在两个肽的整个长度上hydratase-3-hydroxyacyl-coenzyme脱氢酶三官能酶。与Yang等人的工作一致，在fadA内编码的 β 亚基在肽的整个长度上与来自不同真核来源的五个硫解酶基因具有35至45% 完美的同一性。

BACKGROUND & AIMS: :In a patient with temporomandibular disorder who does not respond to conservative treatment, treatment with intra-articular injection of high molecular weight sodium hyaluronate can be suggested. In our study, 27 patients with nonreduced disc displacement were diagnosed clinically and confirmed by magnetic resonance imaging. The age range was from 21 to 63 years old, with a mean of 39.3 years. Two cycles of injection of high molecular weight sodium hyaluronate was performed on alternative weeks. Pain intensity was measured by the visual analog scale. Maximal mouth opening, clicking joint noise, and lateral movement were measured before and after injection for more than 6 months. Reduction of pain intensity and improvement in the maximum mouth opening parameter was statistically significant. In conclusion, this intra-articular injection using high molecular weight sodium hyaluronate looks very positive for patients affected by nonreduced disc displacement and is encouraged to be used as a primary treatment of temporomandibular joint dysfunction.

背景与目标： : 对于对保守治疗无反应的颞下颌疾病患者，建议使用关节内注射高分子量透明质酸钠进行治疗。在我们的研究中，临床诊断出27例椎间盘移位未减少的患者，并通过磁共振成像证实。年龄范围为21至63岁，平均39.3岁。在其他星期进行了两个周期的高分子量透明质酸钠注射。疼痛强度通过视觉模拟量表测量。注射前后6个月以上，测量最大张口，点击关节噪声和侧向运动。疼痛强度的降低和最大张口参数的改善具有统计学意义。总之，这种使用高分子量透明质酸钠的关节内注射对于受椎间盘移位不全影响的患者看起来非常积极，并被鼓励用作颞下颌关节功能障碍的主要治疗方法。

BACKGROUND & AIMS: :Matrix metalloproteinases (MMPs) have been the subject of intense research because of their roles in tumor metastasis and in the rise and spread of degenerative diseases such as osteo- and rheumatoid arthritis. A preliminary class of 140 druglike, small-molecule matrix metalloproteinase-3 inhibitors, intended as starting scaffolds for optimization and synthesis, has been designed in silico using a series of highly predictive three-dimensional quantitative structure-activity relationship models, including comparative molecular field analysis and comparative molecular similarity indices analysis, with docking and scoring. Thalidomide was chosen as the skeleton on which to base the new lead series, as it moderately inhibits MMP-3, is antiangiogenic, and lends itself easily to structural modifications. Most of the new compounds demonstrate medium to high predicted biological activity and good bioavailability as estimated by the octanol-water partition coefficient ClogP. Compound 102 in particular exhibits extremely favorable predicted activity against MMP-3; is moderately bioavailable; satisfies Lipinski's Rule of Five; and shows promise for further optimization, synthesis, and experimental evaluation as a potential adjunct anticancer or antirheumatic therapeutic.

背景与目标： : 基质金属蛋白酶 (MMPs) 由于其在肿瘤转移以及退行性疾病 (如骨关节炎和类风湿性关节炎) 的兴起和传播中的作用而成为深入研究的主题。初步设计了140类药物小分子基质metalloproteinase-3抑制剂，作为优化和合成的起始支架，使用一系列高度预测性的三维定量构效关系模型，包括比较分子场分析和比较分子相似性指数分析，对接和得分。沙利度胺被选为新铅系列的骨架，因为它适度抑制MMP-3，具有抗血管生成作用，并且易于进行结构修饰。根据辛醇-水分配系数ClogP估计，大多数新化合物表现出中等至高的预测生物活性和良好的生物利用度。化合物102尤其表现出对MMP-3极其有利的预测活性; 具有适度的生物利用度; 满足Lipinski的五法则; 并显示出有望进一步优化，合成和实验评估作为潜在的辅助抗癌或抗风湿治疗剂。

BACKGROUND & AIMS: :Apicomplexan parasites are the cause of numerous important human diseases including malaria and AIDS-associated opportunistic infections. Drug treatment for these diseases is not satisfactory and is threatened by resistance. The discovery of the apicoplast, a chloroplast-like organelle, presents drug targets unique to these parasites. The apicoplast-localized fatty acid synthesis (FAS II) pathway, a metabolic process fundamentally divergent from the analogous FAS I pathway in humans, represents one such target. However, the specific biological roles of apicoplast FAS II remain elusive. Furthermore, the parasite genome encodes additional and potentially redundant pathways for the synthesis of fatty acids. We have constructed a conditional null mutant of acyl carrier protein, a central component of the FAS II pathway in Toxoplasma gondii. Loss of FAS II severely compromises parasite growth in culture. We show FAS II to be required for the activation of pyruvate dehydrogenase, an important source of the metabolic precursor acetyl-CoA. Interestingly, acyl carrier protein knockout also leads to defects in apicoplast biogenesis and a consequent loss of the organelle. Most importantly, in vivo knockdown of apicoplast FAS II in a mouse model results in cure from a lethal challenge infection. In conclusion, our study demonstrates a direct link between apicoplast FAS II functions and parasite survival and pathogenesis. Our genetic model also offers a platform to dissect the integration of the apicoplast into parasite metabolism, especially its postulated interaction with the mitochondrion.

背景与目标： : Apicomplexan寄生虫是许多重要人类疾病的病因，包括疟疾和与艾滋病相关的机会性感染。这些疾病的药物治疗并不令人满意，并受到耐药性的威胁。叶绿体样细胞器apicoplast的发现提出了这些寄生虫特有的药物靶标。apicoplast定位脂肪酸合成 (FAS II) 途径是一种与人类类似FAS I途径根本不同的代谢过程，它代表了一个这样的目标。然而，apicoplast FAS II的特定生物学作用仍然难以捉摸。此外，寄生虫基因组还编码用于合成脂肪酸的其他且潜在的冗余途径。我们已经构建了酰基载体蛋白的条件无效突变体，这是弓形虫中FAS II途径的核心组成部分。FAS II的丢失严重损害了寄生虫在培养中的生长。我们显示FAS II是激活丙酮酸脱氢酶所必需的，丙酮酸脱氢酶是代谢前体乙酰辅酶a的重要来源。有趣的是，酰基载体蛋白敲除还导致apicoplast生物发生缺陷，并导致细胞器丢失。最重要的是，在小鼠模型中体内敲除apicoplast FAS II可从致命的攻击感染中治愈。总之，我们的研究证明了apicoplast FAS II功能与寄生虫存活和发病机理之间的直接联系。我们的遗传模型还提供了一个平台，可以将apicoplast整合到寄生虫代谢中，尤其是其与线粒体的假定相互作用。

BACKGROUND & AIMS: :Isolated adrenal cells from Vitamin E-deficient and control rats were prepared by a trypsin digestion method. Cyclic adenosine 3',5'-monophosphate (cyclic AMP) formation was studied in response to adrenocorticotropin (ACTH) in the presence and absence of ascorbate by measuring the conversion of prelabeled adenosine 5'-triphosphate [14C]ATP to cyclic [14C]AMP. Ascorbate (0.5 mM) inhibited ACTH-induced cyclic [14C]AMP formation in adrenal cells isolated from Vitamin E-deficient rats but had no effect in the control cells. The inhibitory effect of ascorbate on ACTH-induced cyclic AMP formation in Vitamin E-deficient rats decreased as the concentration of ACTH increased. In Vitamin E-deficient rats ascorbate inhibited ACTH-induced cyclic [14C]AMP formation after 30 min of incubation. There was no further significant accumulation of cyclic [14C]AMP at 60 min or 120 min although in the absence of ascorbate cyclic [14C]AMP continued to be formed. The in vitro addition of alpha-tocopherol reduced the inhibition of ACTH-induced cyclic [14C]AMP formation by ascorbate in Vitamin E-deficient rats. These studies suggest that alpha-tocopherol and ascorbate may affect ACTH-induced cyclic AMP formation through interaction with the membrane-bound enzyme adenylate cyclase.

背景与目标： : 通过胰蛋白酶消化法从缺乏维生素e的大鼠和对照大鼠中分离出的肾上腺细胞。环腺苷3 '，通过测量预标记的5'-三磷酸腺苷 [14C]ATP向环状 [14C] 的转化，研究了在存在和不存在抗坏血酸的情况下对促肾上腺皮质激素 (ACTH) 的响应5 '-单磷酸 (环状AMP) 的形成。抗坏血酸 (0.5 mM) 抑制ACTH诱导的环状 [14C] 从缺乏维生素e的大鼠中分离出的肾上腺细胞中AMP的形成，但在对照细胞中没有作用。抗坏血酸对缺乏维生素e的大鼠中ACTH诱导的环状AMP形成的抑制作用随着ACTH浓度的增加而降低。在缺乏维生素e的大鼠中，抗坏血酸抑制ACTH诱导的环状 [培养30分钟后形成14C]AMP。在60分钟或120分钟时没有进一步显著的循环 [14C]AMP积累，尽管在没有抗坏血酸环 [14C]AMP继续形成。α-生育酚的体外添加降低了ACTH诱导的循环的抑制 [14C] 抗坏血酸在缺乏维生素e的大鼠中形成AMP。这些研究表明，α-生育酚和抗坏血酸可能通过与膜结合酶腺苷酸环化酶的相互作用影响ACTH诱导的环状AMP形成。

BACKGROUND & AIMS: :Neuronal death associated with cerebral ischemia and hypoglycemia is related to increased release of excitatory amino acids (EAA) and energy failure. The intrahippocampal administration of the glycolysis inhibitor, iodoacetate (IOA), induces the accumulation of EAA and neuronal death. We have investigated by microdialysis the role of exocytosis, glutamate transporters and volume-sensitive organic anion channel (VSOAC) on IOA-induced EAA release. Results show that the early component of EAA release is inhibited by riluzole, a voltage-dependent sodium channel blocker, and by the VSOAC blocker, tamoxifen, while the early and late components are blocked by the glutamate transport inhibitors, L-trans-pyrrolidine 2,4-dicarboxylate (PDC) and DL-threo-beta-benzyloxyaspartate (DL-TBOA); and by the VSOAC blocker 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS). Riluzole, DL-TBOA and tamoxifen did not prevent IOA-induced neuronal death, while PDC and DNDS did. The VSOAC blockers 5-nitro-2-(3-phenylpropyl-amino) benzoic acid (NPPB) and phloretin had no effect either on EAA efflux or neuronal damage. Results suggest that acute inhibition of glycolytic metabolism promotes the accumulation of EAA by exocytosis, impairment or reverse action of glutamate transporters and activation of a DNDS-sensitive mechanism. The latest is substantially involved in the triggering of neuronal death. To our knowledge, this is the first study to show protection of neuronal death by DNDS in an in vivo model of neuronal damage, associated with deficient energy metabolism and EAA release, two conditions involved in some pathological states such as ischemia and hypoglycemia.

背景与目标： : 与脑缺血和低血糖相关的神经元死亡与兴奋性氨基酸 (EAA) 释放增加和能量衰竭有关。海马内给予糖酵解抑制剂碘乙酸 (IOA) 会诱导EAA的积累和神经元死亡。我们通过微透析研究了胞吐作用，谷氨酸转运蛋白和体积敏感的有机阴离子通道 (VSOAC) 对IOA诱导的EAA释放的作用。结果表明，电压依赖性钠通道阻滞剂利鲁唑和VSOAC阻滞剂他莫昔芬抑制了EAA释放的早期成分，而谷氨酸转运抑制剂L-反式吡咯烷2，4-二羧酸 (PDC) 和DL-苏-β-苄氧基天冬氨酸 (DL-TBOA); 并通过VSOAC阻滞剂4,4 '-dinitrostilbene-2，2'-二磺酸 (DNDS)。利鲁唑，DL-TBOA和他莫昔芬不能预防IOA诱导的神经元死亡，而PDC和DNDS可以预防。VSOAC阻滞剂5-硝基-2-(3-苯基丙基-氨基) 苯甲酸 (NPPB) 和根皮素对EAA流出或神经元损伤均无影响。结果表明，糖酵解代谢的急性抑制通过胞吐作用，谷氨酸转运蛋白的受损或逆转作用以及DNDS敏感机制的激活来促进EAA的积累。最新的主要涉及神经元死亡的触发。据我们所知，这是第一项在神经元损伤的体内模型中显示DNDS保护神经元死亡的研究，该模型与能量代谢不足和EAA释放有关，这两种情况涉及某些病理状态，例如缺血和低血糖。

BACKGROUND & AIMS: Sixty-one strains of Mycobacterium tuberculosis complex and 47 strains of nontuberculous mycobacteria were analyzed for fatty acids and enzyme profiles. Cellular fatty acids were extracted from bacteria, methylated and analyzed by gas liquid chromatography operated either manually (Perkin-Elmer) or by the automatic Microbial Identification System. The major cellular fatty acids in all mycobacterial species were C161. Tuberculostearic acid was found in all species with the exception of Mycobacterium gordonae. The fatty acids with a carbon-length longer than 20 could be detected only by conventional gas chromatography. Strains of M.

tuberculosis had a high ratio of C260. For determination of branched-chain fatty acids, the MIS provided more definitive results. The data indicated that the fatty acid profiles could provide rapid species identification. The results of the enzyme profile analysis using API-ZYM strips showed 39 different patterns from 59 strains of M. tuberculosis, and 41 different patterns from 46 nontuberculous mycobacteria strains, suggesting that enzyme profiles can also be used for strain characterization within the same species.

背景与目标： 分析了61株结核分枝杆菌复合物和47株非结核分枝杆菌的脂肪酸和酶谱。从细菌中提取细胞脂肪酸，甲基化，并通过手动 (Perkin-Elmer) 或自动微生物识别系统操作的气相色谱法进行分析。所有分枝杆菌物种中的主要细胞脂肪酸为c161。除gordonae分枝杆菌外，所有物种中均发现了结核硬脂酸。碳长度大于20的脂肪酸只能通过常规气相色谱法检测。结核分枝杆菌菌株的c260比例很高。对于支链脂肪酸的测定，MIS提供了更明确的结果。数据表明，脂肪酸谱可以提供快速的物种鉴定。使用API-ZYM条带进行的酶谱分析结果显示，来自59株结核分枝杆菌的39种不同模式，以及来自46株非结核分枝杆菌的41种不同模式，这表明酶谱也可用于同一物种内的菌株表征。

BACKGROUND & AIMS: :The goal of this study was to evaluate the cleaning ability of three acid irrigating solutions after hand and rotary instrumentation. Eighty human teeth were randomly divided in eight groups. Four groups were prepared with hand instrumentation and other four with ProTaper. The irrigating solutions were 15% citric acid plus 2.5% NaOCl; 15% EDTA plus 2.5% NaOCl; 5% orthophosphoric acid plus 2.5% NaOCl; and 2.5% NaOCl alone as control. Canal walls were observed with scanning electron microscopy, and photomicrographs were taken in apical, middle, and coronal thirds. A scoring system for debris and smear layer was used. Acid solutions with 2.5% NaOCl were effective in the elimination of smear layer or debris, and no significant differences were showed in smear layer removal between techniques. However, 2.5% NaOCl did not remove smear layer or debris, and no significant differences in debris were observed between manual and rotary techniques.

背景与目标： : 这项研究的目的是评估手动和旋转仪器后三种酸灌溉溶液的清洁能力。将80颗人类牙齿随机分为八组。用手动仪器准备了四组，用ProTaper准备了另外四组。灌溉溶液是15% 柠檬酸加2.5% NaOCl; 15% EDTA加2.5% NaOCl; 5% 正磷酸加2.5% NaOCl; 和单独2.5% NaOCl作为对照。用扫描电子显微镜观察管壁，并在根尖，中部和冠状三分之二处拍摄显微照片。使用了碎片和涂抹层的评分系统。具有2.5% NaOCl的酸溶液可有效消除涂片层或碎屑，并且在技术之间的涂片层去除方面没有显示出显着差异。然而，2.5% NaOCl没有去除涂抹层或碎片，并且在手动和旋转技术之间没有观察到碎片的显着差异。

BACKGROUND & AIMS: Pseudomonas putida U does not degrade D-glucose through the glycolytic pathway but requires (i) its oxidation to D-gluconic acid by a peripherally located constitutive glucose dehydrogenase (insensitive to osmotic shock), (ii) accumulation of D-gluconic acid in the extracellular medium, and (iii) the induction of a specific energy-dependent transport system responsible for the uptake of D-gluconic acid. This uptake system showed maximal rates of transport at 30 degrees C in 50 mM potassium phosphate buffer, pH 7.0. Under these conditions the K(m) calculated for D-gluconic acid was 6.7 microM. Furthermore, a different transport system, specific for the uptake of glucose, was also identified. It is active and shows maximal uptake rates at 35 degrees C in 50 mM potassium phosphate buffer, pH 6.0, with a K(m) value of 8.3 microM.

背景与目标： 恶臭假单胞菌U不会通过糖酵解途径降解D-葡萄糖，但需要 (i) 通过位于外周的组成型葡萄糖脱氢酶将其氧化为D-葡萄糖酸 (对渗透休克不敏感)，(ii) D-葡萄糖酸在细胞外培养基中的积累，(iii) 诱导负责吸收D-葡萄糖酸的特定能量依赖性转运系统。该吸收系统在50 mM磷酸钾缓冲液 (pH 7.0) 中显示了在30 ℃ 下的最大转运速率。在这些条件下，计算的D-葡萄糖酸的K(m) 为6.7微米。此外，还确定了特定于葡萄糖摄取的不同转运系统。它具有活性，并在50 mM磷酸钾缓冲液 (pH 6.0) 中的35摄氏度下显示出最大的吸收速率，K(m) 值为8.3微米。

BACKGROUND & AIMS: Recently, 65-kDa glutamic acid decarboxylase (GAD 65) antibodies (GADA) have been introduced as autoimmune markers in blood to confirm the diagnosis of insulin-dependent diabetes mellitus (IDDM). In this study, to evaluate two new assays that use 125I-labeled GAD 65, we assayed samples from 100 children with recent onset of diabetes and 100 control children, the results were compared with those of a [35S]GADA assay and with results for islet cell antibodies (ICA), the conventional autoimmune marker. Receiver operating characteristic (ROC) curve analysis showed one of the new assays (from RSR) to be more sensitive (P = 0.01) than the comparison ([35S]GADA) assay, whereas the second new assay (from Elias) was less sensitive (P < 0.001). The GADA frequency at 97.5% specificity was greatest in the comparison assay63 of 100 vs 41 of 100 (P < 0.01) and 53 of 100 (P = 0.16) in the RSR and Elias assays, respectively. Almost all GADA-positive patients had ICA, but one-third of the ICA-positive patients was GADA-negative. Accordingly, adding GADA analysis results to ICA testing increased the frequency of detection of autoimmune markers only slightly (from 81% to 85%). In conclusion, at 97.5% specificity the [35S]GADA assay seemed to be more efficient than the 125I assays, although the difference was significant only for the Elias 125I assay. Antigen-specific antibodies other than GADA may explain the difference in GADA and ICA frequencies.

背景与目标： 最近，已将65 kDa谷氨酸脱羧酶 (GAD 65) 抗体 (GADA) 作为血液中的自身免疫标记物引入，以确认胰岛素依赖型糖尿病 (IDDM) 的诊断。在这项研究中，为了评估使用125i标记的GAD 65的两种新检测方法，我们分析了100名近期糖尿病发作儿童和100对照儿童的样本，将结果与 [35S]GADA分析的结果进行了比较，并与胰岛细胞抗体 (ICA) 的结果进行了比较，传统的自身免疫标记。受试者工作特征 (ROC) 曲线分析显示，新的检测方法之一 (来自RSR) 比比较 ([35S]GADA) 检测方法更敏感 (P = 0.01)，而第二个新的分析 (来自Elias) 敏感性较低 (P <0.001)。在RSR和Elias分析中，100的63与100的41 (P < 0.01) 和100的53 (P = 0.16) 的比较分析中，GADA频率在97.5% 特异性最高。分别。几乎所有GADA阳性患者都有ICA，但3分之1 ICA阳性患者为GADA阴性。因此，将GADA分析结果添加到ICA测试中仅略微增加了自身免疫标志物的检测频率 (从81% 到85%)。总之，在97.5% 特异性下，[35S]GADA分析似乎比125I分析更有效，尽管差异仅在Elias 125I分析中是显着的。除GADA以外的抗原特异性抗体可以解释GADA和ICA频率的差异。

BACKGROUND & AIMS: :In order to investigate the mode of interaction between the N-quarternized cytosine base and the aromatic amino acid, the crystal structure of the 3-methyl-cytidine-5'-monophosphate:tryptamine complex was analyzed by X-ray diffraction. The complex crystals were stabilized by extensive hydrogen bond formations in which eight independent water molecules per complex pair participated. A prominent stacking interaction, characterized by a parallel alignment of both rings with a separation distance of ca. 3.4 A, was observed between the cytosine base and the indole ring. Combining the present results with X-ray crystallographic data on the adenine--and guanine--aromatic amino acid interactions, we summarize the structural characteristics observed in the stacking interaction of the N-quarternized nucleic acid base with the aromatic amino acid and discuss their biological implications, especially in connection with the significance of N-protonation of nucleic acid base for selective recognition by protein.

背景与目标： : 为了研究N-四分之一化胞嘧啶碱与芳香族氨基酸之间的相互作用模式，通过x射线衍射分析了3-甲基胞苷-5 '-单磷酸: 色胺复合物的晶体结构。复杂的晶体通过广泛的氢键形成而稳定，其中每个复杂对有八个独立的水分子参与其中。在胞嘧啶碱和吲哚环之间观察到显著的堆叠相互作用，其特征是两个环平行排列，分离距离约3.4 A。结合目前的结果与腺嘌呤-和鸟嘌呤-芳香族氨基酸相互作用的x射线晶体学数据，我们总结了在N-四分之一化核酸碱基与芳香族氨基酸的堆叠相互作用中观察到的结构特征，并讨论了它们的生物学意义，特别是与核酸碱基的N-质子化对蛋白质选择性识别的意义有关。

BACKGROUND & AIMS: :Reported here is the synthesis and biological evaluation of the asialoglycoprotein receptor (ASGP-R) targeted fourth generation poliamidoamine dendrimer (G(4)-PAMAM) loaded with sorafenib. The ASGP-R targeted dendrimer was obtained by conjugation of Lactobionic acid (La) to the G(4)-PAMAM dendrimer, followed by acetylation (Ac) of the free amino groups in order to reduce the non-specific interactions with the cell membrane. Moreover, by additionally grafting fluorescein (FITC), it was easy to characterize the internalization pathway and the intracellular fate of the targeted dendrimer Ac-La-G(4)-PAMAM-FITC. In vitro experiments performed on HepG-2 and HLE cell lines, allowed to study the ability of the dendrimers to affect the cell vitality. Confocal microscopy and cytofluorimetric analysis confirmed higher binding and uptake ability of the Ac-La-G(4)-PAMAM-FITC dendrimer in well differentiated and ASGP-R expressing human liver cancer cell line HepG-2 compared non-expressing HLE cells. Ac-La-G(4)-PAMAM-FITC dendrimer loaded with sorafenib was stable and showed sustained sorafenib release. As evidenced by the cytotoxicity studies, sorafenib included in the dendrimer maintained its effectiveness, and was able to produce a longer lasting effect over the time compared to molar equivalent doses of free sorafenib. This new targeted dendrimer appears to be a suitable carrier for the delivery of sorafenib to liver cancer cells expressing ASGP-R.

背景与目标： : 此处报道的是载有索拉非尼的靶向第四代丙酰胺胺树状分子 (G(4)-PAMAM) 的去唾液酸糖蛋白受体 (asgp-r) 的合成和生物学评估。通过将乳糖酸 (La) 与G(4)-PAMAM树状大分子偶联，然后对游离氨基进行乙酰化 (Ac) 以减少非特异性相互作用，从而获得asgp-r靶向的树状大分子细胞膜。此外，通过另外接枝荧光素 (FITC)，很容易表征目标树状分子Ac-La-G(4)-PAMAM-FITC的内化途径和细胞内命运。在HepG-2和HLE细胞系上进行的体外实验允许研究树状大分子影响细胞活力的能力。共聚焦显微镜和细胞荧光分析证实，与未表达的HLE细胞相比，Ac-La-G(4)-PAMAM-FITC树状聚合物在分化良好且表达asgp-r的人肝癌细胞系HepG-2更高的结合和摄取能力。载有索拉非尼的Ac-La-G(4)-PAMAM-FITC树枝状大分子稳定，并显示出持续的索拉非尼释放。正如细胞毒性研究所证明的那样，与摩尔当量剂量的游离索拉非尼相比，包含在树枝状聚合物中的索拉非尼保持了其有效性，并且能够在一段时间内产生更长的持久效果。这种新的靶向树枝状聚合物似乎是将索拉非尼递送到表达asgp-r的肝癌细胞的合适载体。

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： : 在铁缺乏的绝经前妇女中，研究了抗坏血酸对铁生物利用度较低 (含有最少的肉和抗坏血酸) 饮食中铁保留的影响。通过饮食 (5.0 mg Fe/2000 kcal，治疗67-88 d) 和放血术，11名妇女耗尽了储存铁 (由血清铁蛋白指示)。然后，他们食用含有13.7 mg Fe/2000 kcal的饮食，补充有安慰剂或抗坏血酸，每天三次 (总共1500 mg)，并进餐5.5周。抗坏血酸改善了铁的表观吸收 (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，红细胞原卟啉和血清铁，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。在消耗铁的女性中，饮食中预计铁利用率较差，抗坏血酸补充剂可提高5.5周的体内铁保留率。

BACKGROUND & AIMS: :The use of fillers for nonsurgical rhinoplasty has advanced in both materials and methods, and continues to gain popularity in North America. This technique is most often used for secondary revisions, although reports of fillers used in primary rhinoplasty in selected patients have been recently described. The present report details the use of a hyaluronic acid dermal filler in a young Middle Eastern man for a post-traumatic crooked nose deformity. Primary correction of the patient's right-sided nasal bone deviation using hyaluronic acid as a soft tissue filler was achieved with excellent results and patient satisfaction. The current use of fillers in nasal contouring is reviewed.

背景与目标： : 在非手术鼻整形术中使用填充物在材料和方法上都取得了进步，并在北美继续受到欢迎。尽管最近已经描述了在选定患者的初次鼻整形术中使用填充物的报道，但该技术最常用于二次修订。本报告详细介绍了一名中东年轻人在创伤后弯曲鼻子畸形中使用透明质酸皮肤填充剂的情况。使用透明质酸作为软组织填充剂对患者的右侧鼻骨偏斜进行了初步矫正，效果极佳，患者满意。回顾了填充剂在鼻腔轮廓中的当前使用。

BACKGROUND & AIMS: BACKGROUND:Microbial oil is one important bio-product for its important function in energy, chemical, and food industry. Finding suitable substrates is one key issue for its industrial application. Both hydrophilic and hydrophobic substrates can be utilized by oleaginous microorganisms with two different bio-pathways ("de novo" lipid fermentation and "ex novo" lipid fermentation). To date, most of the research on lipid fermentation has focused mainly on only one fermentation pathway and little work was carried out on both "de novo" and "ex novo" lipid fermentation simultaneously; thus, the advantages of both lipid fermentation cannot be fulfilled comprehensively. RESULTS:In this study, corncob acid hydrolysate with soybean oil was used as a mix-medium for combined "de novo" and "ex novo" lipid fermentation by oleaginous yeast Trichosporon dermatis. Both hydrophilic and hydrophobic substrates (sugars and soybean oil) in the medium can be utilized simultaneously and efficiently by T. dermatis. Different fermentation modes were compared and the batch mode was the most suitable for the combined fermentation. The influence of soybean oil concentration, inoculum size, and initial pH on the lipid fermentation was evaluated and 20 g/L soybean oil, 5% inoculum size, and initial pH 6.0 were suitable for this bioprocess. By this technology, the lipid composition of extracellular hydrophobic substrate (soybean oil) can be modified. Although adding emulsifier showed little beneficial effect on lipid production, it can modify the intracellular lipid composition of T. dermatis. CONCLUSIONS:The present study proves the potential and possibility of combined "de novo" and "ex novo" lipid fermentation. This technology can use hydrophilic and hydrophobic sustainable bio-resources to generate lipid feedstock for the production of biodiesel or other lipid-based chemical compounds and to treat some special wastes such as oil-containing wastewater.

背景与目标：