BACKGROUND & AIMS: The effect of bacteriorhodopsin (BR) on the percolation properties of dimyristoylphosphatidylcholine/distearoylphosphatidylcholine bilayers was examined by studying the quenching of a lipid-bound fluorophore by a lipid-bound quencher, and by spin-spin interactions of a nitroxide-labeled lipid using electron spin resonance (ESR). At the low concentrations of BR used, differential scanning calorimetry showed that although the transition enthalpy was reduced in a concentration-dependent manner by incorporation of BR, the solidus and fluidus phase boundaries and overall shape of the heat capacity profiles were essentially unchanged. However, fluorescence quenching and spin-label ESR data showed that the domain topology, as reflected in the percolation properties, is strongly affected by the protein. In contrast to our previous fluorescence data for the pure lipid mixtures, quenching in the coexistence region is independent of the fluid phase fraction when BR is present. In addition, the percolation threshold estimated by spin-label ESR is shifted in the presence of BR to a higher gel phase fraction at a given lipid composition. Both the fluorescence quenching and spin-label ESR data, together with the results of earlier simulations, strongly suggest that the fluid phase domains are substantially larger and/or less ramified in the presence of BR than in its absence. We have previously reported a similar effect of a transmembrane peptide, pOmpA (Escherichia coli outer membrane protein A signal peptide), on fluid domain connectivity in binary phosphatidylcholine mixtures.

背景与目标： 通过研究脂质结合的猝灭剂对脂质结合的荧光团的猝灭以及使用电子自旋的一氧化氮标记的脂质的自旋-自旋相互作用，研究了细菌视紫红质（BR）对二肉豆蔻酰基磷脂酰胆碱/二硬脂酰磷脂酰胆碱双层渗透特性的影响。共振（ESR）。在使用低浓度的BR时，差示扫描量热法显示，尽管通过掺入BR以一定的浓度依赖性降低了转变焓，但固相线和液相线的边界和热容曲线的总体形状基本不变。但是，荧光猝灭和自旋标记ESR数据表明，渗透特性所反映的域拓扑结构受到蛋白质的强烈影响。与我们以前的纯脂质混合物的荧光数据相反，当存在BR时，共存区域的猝灭与液相分数无关。另外，在给定脂质组成下，在BR的存在下，自旋标记ESR估计的渗透阈值会转移到较高的凝胶相分数。荧光猝灭和自旋标记ESR数据以及早期模拟的结果都强烈表明，在存在BR的情况下，与不存在BR的情况相比，液相域的分支和/或分枝显着增加。我们以前曾报道过跨膜肽pOmpA（大肠杆菌外膜蛋白A信号肽）对二元磷脂酰胆碱混合物中的流体域连通性具有类似作用。

BACKGROUND & AIMS: :Previous work has demonstrated the feasibility of in vivo biodiesel synthesis in Escherichia coli, however, ethyl ester formation was dependent on an external fatty acid feedstock. In contrast to E. coli, actinomycetes may be ideal organisms for direct biodiesel synthesis because of their capacity to synthesize high levels of triacylglcerides (TAGs). In this study, we investigated the physiology and associated TAG accumulation along with the in vivo ability to catalyze ester formation from exogenous short chain alcohol sources in Gordonia sp. KTR9, a strain that possesses a large number of genes dedicated to fatty acid and lipid biosynthesis. Total lipid fatty acids content increased by 75 % and TAG content increased by 50 % under nitrogen starvation conditions in strain KTR9. Strain KTR9 tolerated the exogenous addition of up to 4 % methanol, 4 % ethanol and 2 % propanol in the media. Increasing alcohol concentrations resulted in a decrease in the degree of saturation of recovered fatty acid alcohol esters and a slight increase in the fatty acid chain length. A linear dose dependency in fatty alcohol ester synthesis was observed in the presence of 0.5-2 % methanol and ethanol compared to control KTR9 strains grown in the absence of alcohols. An inspection of the KTR9 genome revealed the presence of several putative wax ester synthase/acyl-coenzyme A : diacylglycerol acyltransferase (WS/DGAT) enzymes, encoded by atf gene homologs, that may catalyze the in vivo synthesis of fatty acid esters from short chain alcohols. Collectively, these results indicate that Gordonia sp. KTR9 may be a suitable actinomycete host strain for in vivo biodiesel synthesis.

背景与目标： ：先前的工作证明了在大肠杆菌中体内生物柴油合成的可行性，但是，乙酯的形成取决于外部脂肪酸原料。与大肠杆菌相反，放线菌可能是直接生物柴油合成的理想生物，因为它们能够合成高含量的三酰基甘油（TAGs）。在这项研究中，我们调查了生理和相关的TAG积累以及体内催化Gordonia sp。中外源短链醇源形成酯的能力。 KTR9，具有大量致力于脂肪酸和脂质生物合成的基因的菌株。在氮饥饿条件下，菌株KTR9的总脂质脂肪酸含量增加了75％，TAG含量增加了50％。菌株KTR9耐受培养基中外源添加多达4％的甲醇，4％的乙醇和2％的丙醇。醇浓度的增加导致回收的脂肪酸醇酯的饱和度降低，并且脂肪酸链长度略微增加。与在不存在醇的情况下生长的对照KTR9菌株相比，在存在0.5-2％的甲醇和乙醇的条件下观察到脂肪醇酯合成的线性剂量依赖性。对KTR9基因组的检查发现存在一些推定的蜡酯合酶/酰基辅酶A：二酰基甘油酰基转移酶（WS / DGAT）酶，这些酶由atf基因同源物编码，可能催化体内短链脂肪酸酯的合成酒精。总的来说，这些结果表明Gordonia sp。 KTR9可能是适合体内生物柴油合成的放线菌宿主菌株。

BACKGROUND & AIMS: :The objective of this study was to prepare a 72 h-release formulation of silybin (72 h-SLB) using a combination of solid dispersion, gel matrix and porous silica nanoparticles (PSNs) and to investigate the in vitro/in vivo correlations (IVIVCs). The results of scanning electron microscopy and N(2) adsorption demonstrated that empty PSNs possessed a spherical shape, a highly porous structure, a large specific surface area (385.89 ± 1.12 m(2)/g) and a small pore size (2.74 nm on average). The in vitro dissolution profiles of both 72 h-SLB and silybin-loaded PSNs in different concentrations (0.01, 0.06 and 0.08M) of Na(2)CO(3) solutions revealed that 0.06 M Na(2)CO(3) solution was the optimal medium in which silybin could be released from 72 h-SLB with first-order release kinetics and from PSNs with Higuchi kinetics. Furthermore, the IVIVCs of 72 h-SLB and silybin-loaded PSNs in beagle dogs were also established. Using 0.06 M Na(2)CO(3) solution as the in vitro dissolution medium, a good linear relationship could be achieved for both 72 h-SLB and silybin-loaded PSNs. The findings support the fact that the 72 h-SLB (consisting of solid dispersion, regular gel matrix and PSNs) together with Na(2)CO(3) solution as an in vitro dissolution medium can be developed into a promising formulation for poorly soluble drugs, which enjoys a good IVIVC.

背景与目标： ：这项研究的目的是使用固体分散体，凝胶基质和多孔二氧化硅纳米粒子（PSN）的组合制备水飞蓟宾（72 h-SLB）的72 h释放制剂，并研究体内/体外相关性（ IVIVC）。扫描电子显微镜和N（2）吸附的结果表明，空的PSN具有球形，高度多孔的结构，较大的比表面积（385.89±1.12 m（2）/ g）和较小的孔径（2.74 nm）一般）。 Nah（2）CO（3）解决方案中不同浓度（0.01、0.06和0.08M）的72 h-SLB和水飞蓟宾加载的PSNs的体外溶出曲线显示0.06 M Na（2）CO（3）解决方案是最佳的培养基，其中水飞蓟宾可以从72 h-SLB中以一级释放动力学释放，而从PSN中以Higuchi动力学释放。此外，还建立了比格犬中72 h-SLB和水飞蓟宾的PSN的IVIVC。使用0.06 M Na（2）CO（3）解决方案作为体外溶出介质，可以为72 h-SLB和水飞蓟宾加载的PSNs都实现良好的线性关系。这些发现支持以下事实：72 h-SLB（由固体分散体，规则的凝胶基质和PSN组成）与Na（2）CO（3）解决方案一起作为体外溶出介质，可以开发为溶解性较差的有前途的制剂药物，享有良好的IVIVC。

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： 背景：微生物油因其在能源，化工和食品工业中的重要作用而成为一种重要的生物产品。寻找合适的基材是其工业应用的关键问题之一。具有两种不同生物途径（“从头”脂质发酵和“从头”脂质发酵）的油脂性微生物均可利用亲水性和疏水性底物。迄今为止，大多数关于脂质发酵的研究主要集中在仅一种发酵途径上，并且很少同时进行“从头”和“从头”脂质发酵的工作。因此，不能同时实现两种脂质发酵的优点。
结果：在这项研究中，玉米芯酸与大豆油的水解产物被用作混合培养基，用于油脂性酵母曲氏菌（Trichosporon dermatis）的“从头”和“从头”组合脂质发酵。皮肤癣菌可同时有效地利用培养基中的亲水性和疏水性底物（糖和大豆油）。比较了不同的发酵模式，分批模式最适合组合发酵。评估了豆油浓度，接种量和初始pH值对脂质发酵的影响，并且20 g / L豆油，5％接种量和pH初始值6.0适用于该生物过程。通过该技术，可以修饰细胞外疏水性底物（大豆油）的脂质组成。尽管添加乳化剂对脂质的产生几乎没有有益作用，但它可以改变皮肤炎球菌的细胞内脂质组成。
结论：本研究证明了“从头”和“从头”脂质发酵相结合的潜力和可能性。该技术可以利用亲水和疏水的可持续生物资源来生产脂质原料，以生产生物柴油或其他基于脂质的化合物，并处理某些特殊废物，例如含油废水。

BACKGROUND & AIMS: :The leaves of «moderately hardy» (spinach), «very hardy» (ivy) and «extremely hardy» (spruce) plants [classification according to Levitt {1980)] show characteristic differences with respect to changes in membrane lipid composition and chloroplast ultrastructure which are correlated with the degree of the frost resistance achieved by each type of tissue during adaptation to sub-zero temperatures. Spinach leaves showed no increase in their total lipid content upon frost hardening. On the contrary, the amount of galactolipids decreased considerably, whereas that of phospholipids only slightly increased. No shift from the saturated palmitic acid to the three-fold unsaturated linolenic acid was observed. The membrane lipid content of ivy leaves and spruce needles increased to a similar extent during frost hardening. However, in contrast to spruce needles, a distinct preferential accumulation of the phospholipids was observed in ivy leaves, resulting in an increased PL/GL ratio. A considerable shift from saturated (palmitic) to unsaturated fatty acids was detected in both plants, due mainly to an increase in the proportion of linoleic acid in ivy and of linolenic acid in spruce. In spite of the considerable increase in lipid content, no increase in chloroplast number per cell could be detected in ivy leaves, although the length of the thylakoids was nearly doubled and the plastids appeared to be in a division stage: however, no real division could ever be observed. On the contrary, an increase in the number of chloroplasts and mitochondria was observed in spruce needles. Membrane augmentation became further evident by the many large invaginations of the chloroplast envelope formed when the frost-hardened leaves of ivy or spruce were exposed to sub-zero temperatures which they could just survive.

背景与目标： ：“中等硬度”（菠菜），“极度坚硬”（ivy）和“极度坚硬”（云杉）植物的叶子[根据Levitt（1980）分类）在膜脂成分和叶绿体变化方面表现出特征差异超微结构，与适应零度以下温度时每种组织的抗冻性程度有关。霜冻硬化后，菠菜叶的总脂质含量没有增加。相反，半乳糖脂的量显着减少，而磷脂的量仅略有增加。没有观察到从饱和的棕榈酸到三倍的不饱和亚麻酸的转变。在霜冻硬化过程中，常春藤叶和云杉针的膜脂含量增加了相似的程度。然而，与云杉针头相反，在常春藤叶中观察到磷脂的明显优先积累，从而导致PL / GL比增加。在这两种植物中均检测到从饱和（棕榈酸）到不饱和脂肪酸的显着变化，这主要是由于常春藤中亚油酸和云杉中亚麻酸的比例增加。尽管脂质含量显着增加，但常春藤叶片的叶绿体数量却没有增加，尽管类囊体的长度几乎增加了一倍，质体似乎处于分裂阶段：但是，不能进行真正的分裂曾经被观察到。相反，在云杉针头中观察到叶绿体和线粒体数量增加。当常春藤或云杉的冻干叶子暴露于零度以下的温度下就可以生存时，叶绿体包膜的许多大的侵入使膜增强变得更加明显。

BACKGROUND & AIMS: :We tried to evaluate the possible involvement of fetuin in the scavenger receptors (SRs)-mediated hepatic uptake of polystyrene nanospheres with the size of 50 nm (NS-50), which has surface negative charge (zeta potential=-21.8+/-2.3 mV). The liver perfusion studies in rats revealed that the hepatic uptake of NS-50 pre-coated with fetuin (NS-50-fetuin) was significantly inhibited by poly inosinic acid (poly I), a typical inhibitor of SRs, whereas that of plain NS-50 or NS-50 pre-coated with BSA (NS-50-BSA) was not. The uptake of NS-50-fetuin by cultured Kupffer cells was also significantly inhibited by poly I, and anti-class A scavenger receptors (SR-A) antibody, suggesting that fetuin on NS-50 mediated the recognition and internalization of NS-50 by Kupffer cells and at least SR-A would be responsible for the uptake. Taken that Western blot analysis confirmed that fetuin certainly adsorbed on the surface of NS-50 after the incubation of NS-50 with serum, the results obtained in the present study indicate that fetuin would be one of the serum proteins that were substantially involved in the hepatic uptake of NS-50 via SRs.

背景与目标： ：我们试图评估胎球蛋白可能参与清道夫受体（SRs）介导的肝脏吸收大小为50 nm（NS-50）的聚苯乙烯纳米球，该表面具有表面负电荷（ζ电位= -21.8 /-2.3 mV）。在大鼠的肝脏灌注研究中发现，典型的SR抑制剂聚肌苷酸（poly I）可显着抑制预先涂有胎球蛋白（NS-50-胎球蛋白）的NS-50的肝吸收。未预涂BSA的-50或NS-50（NS-50-BSA）。聚I和抗A类清道夫受体（SR-A）抗体也显着抑制了培养的Kupffer细胞对NS-50-胎球蛋白的摄取，表明NS-50上的胎球蛋白介导了NS-50的识别和内在化。枯否细胞的吸收，至少由SR-A引起。认为Western印迹分析证实胎球蛋白在将血清与NS-50孵育后肯定吸附在NS-50的表面上，本研究获得的结果表明胎球蛋白将是实质性参与胎盘蛋白的血清蛋白之一。肝通过SRs吸收NS-50。

BACKGROUND & AIMS: :Solid and papillary epithelial neoplasm (SPENP) of the pancreas is a rare pancreatic tumour of low malignant potential, that is seen mostly in young females. The aetiology and pathogenesis is unclear but it is considered to be arising from primordial pancreatic cells. We report two cases of SPENP who had palpable abdominal lumps and were diagnosed on histopathology. In the first case, the tumour was unresectable and patient died within one year. In the second case, at laprotomy the patient had perineurial as well as capsular infiltration but after wide resection of the growth, patient has been doing well for the past 6 months. Since SPENP is a low grade malignant neoplasm, it should be treated aggressively with complete resection and metastatectomy. Prognosis after adequate surgery is good. A clinicopathological study and brief review of literature is presented.

背景与目标： ：胰腺的乳头状和乳头状上皮性肿瘤（SPENP）是一种罕见的低恶性潜能的胰腺肿瘤，多见于年轻女性。病因和发病机制尚不清楚，但被认为起源于原始胰腺细胞。我们报告了2例SPENP患者，他们有明显的腹部肿块，并经组织病理学确诊。在第一种情况下，肿瘤无法切除，患者在一年内死亡。在第二种情况下，在腹膜切开术中，患者有尿道周和囊膜浸润，但是在广泛切除生长后，患者在过去的6个月中一直表现良好。由于SPENP是低度恶性肿瘤，因此应通过彻底切除和转移切除术积极治疗。适当手术后预后良好。提出了临床病理学研究和文献简要回顾。

BACKGROUND & AIMS: It has been established that oxidized LDL (ox-LDL) modifies cytokine secretion by macrophages, for example, by reducing tumor necrosis factor alpha (TNF-(alpha) m-RNA. However, little is known about the effects of oxidized high density lipoprotein (ox-HDL). This study reports the effects of ox-HDL subfractions 2 and 3 (ox-HDL2, ox-HDL3) compared with that of ox-LDL and some products of oxidation (hydroperoxides and aldehydes) on the secretion of TNF-alpha from THP-1 human monocytes derived macrophages in vitro. HDL2, HDL3 and LDL were oxidized with 10 microM Cu++ for 12 h and/or 24 h. Native and oxidized HDL and LDL were incubated for 24 h with macrophages with or without LPS (10 ng/ml) after which TNF-alpha secretion was measured in the culture medium. Lipid hydroperoxides and apolar aldehydes were also incubated with the cells for 2 h following which the medium was replaced and TNF-alpha secretion measured after a further 22 h of incubation. An inhibition of TNF-alpha by ox-HDL2 (p < .05), ox-HDL3 (p < .05) and ox-LDL (p < .05) from THP-1 macrophages was observed in the presence and absence of LPS. This inhibition remained the same after incubation with ox-HDL 12 h and 24 h. Hydroperoxides of linoleic acid did not modify TNF-alpha secretion by cells while five out of eight aldehydes analyzed (2,4-heptadienal, hexanal, 2-nonenal, 2-octenal, 2,4-decadienal) inhibited TNF-alpha secretion (p < .05). These findings demonstrate that ox-HDL, and some of its lipid peroxidation products, plays a role in the modulation of the inflammatory response by macrophages as previously observed for ox-LDL.

背景与目标： 已经确定氧化的LDL（ox-LDL）可以通过减少肿瘤坏死因子α（TNF-αm-RNA）来调节巨噬细胞的细胞因子分泌。但是，对氧化的高密度脂蛋白的作用知之甚少（ox-HDL）。这项研究报告了与ox-LDL和某些氧化产物（氢过氧化物和醛类）相比，ox-HDL亚组分2和3（ox-HDL2，ox-HDL3）对TNF分泌的影响THP-1人单核细胞衍生的α-α体外，将HDL2，HDL3和LDL用10 microM Cu氧化12 h和/或24 h，将天然和氧化的HDL和LDL与有或没有LPS的巨噬细胞一起孵育24 h （10 ng / ml），然后在培养基中测量TNF-α的分泌，脂质过氧化氢和非极性醛也与细胞一起孵育2小时，然后更换培养基，再过22 h后测量TNF-α的分泌ox-HDL2对TNF-α的抑制作用（p < .05），在存在和不存在LPS的情况下观察到THP-1巨噬细胞的ox-HDL3（p <.05）和ox-LDL（p <.05）。与ox-HDL孵育12小时和24小时后，这种抑制作用保持不变。亚油酸的氢过氧化物不会改变细胞的TNF-α分泌，而分析的八种醛中的五种（2,4-庚二烯醛，己醛，2-壬烯醛，2-辛烯醛，2,4-癸二烯醛）抑制TNF-α分泌（p <.05）。这些发现表明，ox-HDL及其某些脂质过氧化产物在巨噬细胞对炎症反应的调节中起着作用，正如以前对ox-LDL所观察到的一样。

BACKGROUND & AIMS: The present study was conducted to clarify the mechanism of toxicity of organic compounds using lipid model membranes (liposomes and planar lipid membranes). The compounds studied were trialkyltin and trialkyllead chlorides, dialkyltin dichlorides and some inorganic forms of those metals. Two different (anionic and cationic) detergents were also used in the experiments to change the surface properties of liposomes. As a measure of interaction between the compounds studied and model membranes were the release of liposome bound praseodymium and the change in stability of planar membranes under the influence of those compounds. On the basis of the results obtained it was postulated that the mechanism of interaction between tin- and leadorganics and model lipid membranes is a combination of different factors featuring interacting sides. The most important properties determining the behaviour of organic compounds in the interaction were lipophilicity and polarity of different parts of the organics and the steric arrangement they can take in the medium. On the other hand, the surface potential of the lipid bilayer and the environment of the lipid molecules, that play a significant role in the availability of the lipid bilayer to the organics, were important factors in the interaction.

背景与目标： 进行本研究以阐明使用脂质模型膜（脂质体和平面脂质膜）的有机化合物的毒性机理。所研究的化合物为三烷基锡和三烷基氯化铅，二烷基二氯化锡和这些金属的某些无机形式。实验中还使用了两种不同的（阴离子和阳离子）去污剂来改变脂质体的表面性质。脂质体结合的ody的释放以及在这些化合物的影响下平面膜稳定性的变化是衡量所研究化合物与模型膜之间相互作用的一种量度。根据获得的结果，假设锡和铅有机物与模型脂质膜之间的相互作用机理是具有相互作用侧的不同因素的组合。决定有机化合物在相互作用中的行为的最重要特性是亲脂性和有机物不同部分的极性以及它们在介质中可采取的空间排列。另一方面，脂质双层的表面电势和脂质分子的环境在脂质双层对有机物的利用中起着重要作用，是相互作用的重要因素。

BACKGROUND & AIMS: :Under both conventional method (CM) and microwave (MW) irradiation (MWI) conditions, alkylation of 4,5-diphenylimidazole-2-thione (1) with halogeno-alkanols 2 or 5, chloroglycerol 11 and 2,3-O-isopropylidene-1-O-(p-tolylsulfonyl)-glycerol (8) in presence of sodium ethoxide or sodium acetate in alcohol afforded regioselectively the corresponding S-alkylated analogues 3, 6, 9, and 12; they also were obtained using MW in absence and presence of bentonite as solid support with no change in regioselectivity. In the presence of potassium carbonate in DMF, the bisalkylated analogues 4, 7, 10, and 13 were obtained except in case of compound 13 where it was accompanied with the imidazothiazine 14. A convenient approach for imidazo-[2,1-b]thiazines and thiazoles 14-16 could be achieved by intramolecular dehydrative ring closure of the S-hydroxyalkylated imidazoles 3, 6, and 12 using potassium carbonate in DMF under both conventional and microwave methods. Isopropylidenation of 12 and 13 and deprotection of 9 and 10 also were investigated.

背景与目标： ：在常规方法（CM）和微波（MW）照射条件下，均用卤代链烷醇2或5，氯甘油11和2,3-O-将4,5-二苯基咪唑-2-硫酮（1）烷基化在乙醇钠或乙酸钠存在下，在异丙醇中的异亚丙基-1-O-（对甲苯磺酰基）-甘油（8）选择性地提供相应的S-烷基化的类似物3、6、9和12；它们也可以在不存在和存在膨润土作为固体载体的情况下使用MW获得，其区域选择性没有变化。在DMF中存在碳酸钾的情况下，获得双烷基化的类似物4、7、10和13，除了化合物13与咪唑并噻嗪14结合的情况外。咪唑-[2,1-b]的简便方法噻嗪和噻唑14-16可以通过在传统方法和微波方法下使用碳酸钾在DMF中对S-羟烷基化的咪唑3、6和12进行分子内脱水闭环来实现。还研究了12和13的异亚丙基化和9和10的脱保护。

BACKGROUND & AIMS: :To determine the efficacy and safety of adding ezetimibe to maximally tolerated lipid lowering therapy in patients with HIV dyslipidemia. Retrospective analysis of lipid parameters was conducted for 33 patients with HIV who had been prescribed ezetimibe 10 mg per day. Mean total cholesterol was reduced 21% (p < 0.001). Mean LDL was reduced 35% (p < 0.001). Mean HDL increased 8% (p = 0.038). Mean triglyceride was reduced 34% (p = 0.006). Mean Apolipoprotein B100 was reduced 33% (p = 0.043). No adverse events occurred. Ezetimibe appears safe and effective in patients with HIV when added to maximally tolerated doses of lipid lowering therapy.

背景与目标： ：为了确定在HIV血脂异常患者中最大耐受性降脂治疗中添加依折麦布的疗效和安全性。回顾性分析了33名HIV病人，这些病人每天服用处方依泽替米贝10 mg。平均总胆固醇降低了21％（p <0.001）。平均LDL降低了35％（p <0.001）。平均HDL增加8％（p = 0.038）。平均甘油三酸酯减少了34％（p = 0.006）。平均载脂蛋白B100降低了33％（p = 0.043）。没有发生不良事件。当加入最大耐受剂量的降脂治疗时，依泽替米贝在HIV患者中似乎是安全有效的。

BACKGROUND & AIMS: :Lethal ventricular tachyarrhythmia (LVTA) is the most prevalent electrophysiological underpinning of sudden cardiac death (SCD), a condition that occurs in response to multiple pathophysiological abnormalities. The aim of this study was to identify common lipid features of LVTA that were induced by distinct pathophysiological conditions, thereby facilitating the discovery of novel SCD therapeutic targets. Two rat LVTA-SCD models were established to mimic myocardial infarction (MI) and myocardial ion channel diseases. Myocardial and serum specimens were analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based lipidomics. The lipid profiles of the myocardial and serum specimens were similar between the models. Eleven myocardial lipid classes were altered, including downregulations of: cardiolipin, ceramide, phosphatidylinositol, phosphatidylethanolamine, triacylglycerol, diacylglycerol, phosphatidylglycerol, lysophosphatidylethanolamine and phosphatidylserine, and upregulations of: lysophosphatidylcholine and phosphatidic acid. Serum concentrations of triacylglycerol, lysophosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol were also altered. Alterations of lipids in paired myocardia and sera were closely correlated. Cardiolipin 70:5, cardiolipin 74:9 and ceramide d34:2 were tested as potential biomarkers of LVTA. The results indicate that there are common LVTA lipid profiles induced by MI and myocardial ion channel diseases, potentially offering novel LVTA-SCD therapeutic targets.

背景与目标： ：致命性室性心律失常（LVTA）是心脏猝死（SCD）的最普遍的电生理基础，这种情况是由于多种病理生理异常而引起的。这项研究的目的是确定由不同的病理生理条件诱导的LVTA的常见脂质特征，从而促进新的SCD治疗靶标的发现。建立了两种大鼠LVTA-SCD模型来模拟心肌梗塞（MI）和心肌离子通道疾病。使用基于超高效液相色谱-质谱（UPLC-MS）的脂质组学分析心肌和血清标本。在两个模型之间，心肌和血清标本的脂质谱相似。改变了11种心肌脂质的类别，包括下调心磷脂，神经酰胺，磷脂酰肌醇，磷脂酰乙醇胺，三酰基甘油，二酰基甘油，磷脂酰甘油，溶血磷脂酰乙醇胺和磷脂酰丝氨酸，以及溶血磷脂酰磷酸的上调。血清三酰甘油，溶血磷脂酰胆碱，磷脂酰乙醇胺和磷脂酰肌醇的浓度也发生了改变。配对的心肌和血清中脂质的变化密切相关。心磷脂70：5，心磷脂74：9和神经酰胺d34：2被测试为LVTA的潜在生物标志物。结果表明存在由MI和心肌离子通道疾病引起的常见LVTA脂质谱，可能提供新的LVTA-SCD治疗靶标。

BACKGROUND & AIMS: :Among currently identified issues presenting risks and benefits to human and ocean health, engineered nanoparticles (ENP) represent a priority. Predictions of their economic and social impact appear extraordinary, but their release in the environment at an uncontrollable rate is in striking contrast with the extremely limited number of studies on environmental impact, especially on the marine environment. The sea urchin has a remarkable sensing environmental system whose function and diversity came into focus during the recent years, after sea urchin genome sequencing. The complex immune system may be the basis wherefore sea urchins can adapt to a dynamic environment and survive even in hazardous conditions both in the adult and in the embryonic life. This review is aimed at discussing the literature in nanotoxicological/ecotoxicological studies with a focus on stress and innate immune signaling in sea urchins. In addition, here we introduce our current development of in vitro-driven probes that could be used to dissect ENP aftermaths, suggesting their future use in immune-nanotoxicology.

背景与目标： ：在目前发现的对人类和海洋健康构成风险和益处的问题中，工程纳米颗粒（ENP）成为重中之重。对它们的经济和社会影响的预测似乎非同寻常，但它们以不可控制的速度释放到环境中，与对环境影响，特别是对海洋环境的研究数量极为有限形成鲜明对比。在海胆基因组测序之后，海胆具有卓越的传感环境系统，近年来其功能和多样性成为人们关注的焦点。复杂的免疫系统可能是海胆能够适应动态环境并在成年和胚胎生命中甚至在危险条件下生存的基础。这篇综述旨在讨论纳米毒理学/生态毒理学研究的文献，重点是海胆中的压力和先天性免疫信号传导。此外，在这里，我们介绍了体外驱动探针的最新进展，该探针可用于剖析ENP后果，表明它们在免疫纳米毒理学中的未来用途。

BACKGROUND & AIMS: BACKGROUND:Fine needle aspiration (FNA) cytology has been widely used for pathologic assessment of breast lesions. However, the examination suffers a risk of false-negative results owing to insufficient sample volumes, inaccurate sampling positions, nondefinitive cytologic features, or suboptimal cell preservation. One approach to improve its accuracy is using modern mass spectrometry to detect disease biomarkers, of which the tissue samples are collected through FNA. METHODS:The biological compounds in the FNA tissue samples were extracted and characterized by matrix-assisted laser desorption ionization time-of-flight/mass spectrometry (MALDI-TOF/MS). The results were further analyzed by principal component analysis. Distribution of lipid biomarkers on tissues was explored by imaging mass spectrometry. RESULTS:Lipid profiles of the tissue samples collected by FNA were rapidly obtained through MALDI-TOF/MS analysis. Phosphatidylcholines and triacylglycerols were detected as the predominant compounds in cancerous and normal regions, respectively. The samples were clearly classified by principal component analysis, based on the differences in their lipid profiles. Different lipid patterns were clearly viewed through the molecular imaging of normal and tumorous regions of breast tissue samples. CONCLUSION:The FNA-MALDI-TOF/MS approach can provide complementary information for pathological examinations and improve the accuracy of breast cancer diagnoses. Owing to the ease of operation and automation, it is possible to efficiently screen the lipid biomarkers in a large number of tissue samples by means of MALDI-TOF/MS.

背景与目标： 背景：细针穿刺（FNA）细胞学检查已被广泛用于乳腺病变的病理评估。但是，由于样品量不足，采样位置不正确，细胞学特征不确定或细胞保存效果欠佳，检查可能会出现假阴性结果。一种提高其准确性的方法是使用现代质谱检测疾病生物标志物，其中的组织样本是通过FNA收集的。
方法：通过基质辅助激光解吸电离飞行时间/质谱（MALDI-TOF / MS）提取FNA组织样品中的生物化合物并进行表征。通过主成分分析进一步分析结果。通过成像质谱研究脂质生物标志物在组织上的分布。
结果：通过MALDI-TOF / MS分析快速获得了通过FNA收集的组织样品的脂质概况。磷脂酰胆碱和三酰基甘油分别作为癌性和正常区域中的主要化合物被检测到。根据样品的脂质谱差异，通过主成分分析将样品明确分类。通过对乳腺组织样本的正常和肿瘤区域进行分子成像，可以清楚地观察到不同的脂质模式。
结论：FNA-MALDI-TOF / MS方法可为病理检查提供补充信息，并提高乳腺癌诊断的准确性。由于操作和自动化的简便性，可以通过MALDI-TOF / MS有效地筛查大量组织样品中的脂质生物标志物。

BACKGROUND & AIMS: :To maximize the biomass and lipid production for applications in food or biofuel feedstock, nine stress conditions were tested considering N and/or P limitations, light intensity & quality, for Haematococcus pluvialis SCCAP K-0084 cultivation. Photosynthetically active radiation (PAR), warm white light emitting diode (WWLED), and white light emitting diode (WLED) at illumination of 240 μmol photons m(-2) sec(-1) were the best stress-regulatory factors. PAR without P & low N conditions yielded high biomass with 33% lipids containing increased C16:0 and C18:0 saturated fatty acids, and reduced unsaturated fatty acids (UFAs) (oleic, linoleic, and α/γ-linolenic). WWLED and WLED without P conditions also yielded high biomass, but 25% lipids with increased amounts of UFAs. Red light emitting diode (RLED) without P & low N conditions yielded 46% lipids with lowest biomass. PAR and WWLED & WLED illuminated conditions were found suitable respectively for biodiesel feedstock lipids and UFA-rich lipids for multiple applications.

背景与目标： ：为了使生物质和脂质的生产最大化以用于食品或生物燃料原料，测试了九种胁迫条件，考虑了氮和/或磷的限制，光强度和质量，适用于雨生红球菌SCCAP K-0084的培养。在240μmol光子m（-2）sec（-1）的光照下，光合有效辐射（PAR），暖白光发光二极管（WWLED）和白光发光二极管（WLED）是最佳的应力调节因子。没有P和低N条件的PAR产生了高生物量，其中33％的脂质包含增加的C16：0和C18：0饱和脂肪酸，以及减少的不饱和脂肪酸（UFAs）（油酸，亚油酸和α/γ-亚麻酸）。没有P条件的WWLED和WLED也产生高生物量，但是25％的脂质具有增加的UFA含量。没有P和低N条件的红色发光二极管（RLED）产生了46％的脂质，具有最低的生物量。发现PAR和WWLED和WLED照明的条件分别适合于生物柴油原料脂质和富含UFA的脂质的多种应用。