Chiral samarium iodo and terbutylate derivatives as catalysts for MPV ketone reductions

Samarium iodo and terbutylate derivatives coordinated by various chiral ligands have been prepared and used in situ as new catalysts for MPV reductions of aromatic ketones. The most active catalyst is samarium terbutylate binaphtolate albeit with moderate enantioselectivity.     

PLT,MPV,PDW对单采血小板产品聚集的影响

目的：探讨血小板含量（PLT）,血小板平均分布宽度（PDW）,血小板平均体积（MPV）对单采血小板聚集的影响,方法：随机抽取68例血小板捐献者,均成功捐献单采血小板,分为聚集组和对照组。献血前抽取静脉血,采用麦道尼克CA620血细胞分析仪进行血细胞分析,检测PLT,MPV,PDW。结果：聚集组（%）PDW 17.5±1.8,高于对照组（%）PDW12.1±0.9（P〈0.05）。聚集组（fl）MPV 11.0±0.9高于对照组（fl）MPV 7.8±0.8（P〈0.05）,差异有统计学意义,聚集组PLT（187±13.3）×109,对照组PLT（195±11.0）×109,二者无明显统计学差异（P〉0.05）。MPV,PDW分别与PLT进行相关性分析,PLT与MPV无显著相关（r=0.132,P〉0.05）;PLT与PDW无显著相关（r=0.147,P〉0.05）。结论：单采血小板产品出现聚集,其捐献者PDW,MPV高于单采产品正常捐献者,与献血者PLT计数无明显关系。     

急性心理应激下血小板活化参数的变化及其机制探讨

目的:探讨急性心理应激下健康人群血小板活化参数的变化及其与性别、年龄的相关性,并分析其可能的机制。方法:检测54名健康被试者急性心理应激前后的血小板四项变化,包括血小板计数(PLT)、血小板平均体积(MPV)、血小板分布宽度(PDW)和大血小板比率(P-LCR)。随后,将被试者分成男、女性组或中、老年组,对其血小板四项结果进行组内及组间比较。结果:急性心理应激可导致健康人群中MPV、PDW和P-LCR的显著增加(P0.05),但年龄分组或性别分组组间均未见显著差异(P0.05)。结论:实验性急性心理应激可导致健康人群血小板活化指标MPV、PDW和P-LCR的显著增加,但与年龄和性别无关。     

颈动脉超声定量参数联合MPV/PC比值、NLR对急性缺血性脑卒中患者预后不良的预测价值

摘要 目的：探讨颈动脉超声定量参数联合平均血小板体积（MPV）/血小板计数（PC）比值、中性粒细胞/淋巴细胞比值（NLR）对急性缺血性脑卒中（AIS）患者预后不良的预测价值。方法：选择2020年3月至2022年3月合肥市第二人民医院收治的97例AIS患者,所有患者均行颈动脉超声检查和血常规检查,获得颈动脉超声定量参数,计算MPV/PC比值、NLR。出院后90 d采用改良Rankin量表（mRS）评估患者预后,将患者分为预后不良组和预后良好组。受试者工作特征（ROC）曲线分析颈动脉超声定量参数、MPV/PC比值、NLR联合预测AIS患者预后不良的价值。结果：预后不良组动脉内膜中层厚度（IMT）、舒张末期血流速度（EDV）、MPV/PC比值、NLR大于预后良好组（P＜0.05）,收缩期峰值血流速度（PSV）小于预后良好组（P＜0.05）。IMT、PSV、EDV、MPV/PC比值、NLR预测AIS患者预后不良的曲线下面积分别为0.751、0.710、0.693、0.769、0.771,联合IMT、PSV、EDV、MPV/PC比值、NLR预测AIS患者预后不良的曲线下面积为0.883,高于单独指标预测。结论：颈动脉超声定量参数联合MPV/PC比值、NLR在AIS患者预后不良评估中具有较高的预测价值。     

Pelvic anti-predator armour reduction in Norwegian populations of the threespine stickleback: a rare phenomenon with adaptive implications?

In order to search for armour reductions in the anti-predator armour apparatus of the threespine stickleback Gasterosteus aculeatus , we studied populations from 200 coastal lakes and 32 marine and estuarine sites in Norway. We scored the presence of reductions in the pelvic apparatus in these populations, measured the length of the second dorsal fin and pelvic spine and counted lateral plates in a subset of 96 populations. Then we looked for the relation between pelvic reduction and number of lateral plates and lengths of the second dorsal spine and pelvic spine. We also observed whether pelvic reduced fish had asymmetric development on the right or the left side of the pelvis. Pelvic reduction was not found in marine and estuarine sticklebacks (with one single exception), but in freshwater it occurred in four out of 200 lakes. The amount of pelvic reduction differed from 5% to 68% in the four populations. There appears to be a correlation between pelvic reduction and spine lengths at the population level, but not plate number. Further, it appears to be difficult to explain the occurrence of pelvic reduction in Norway with the factors proposed to be responsible for pelvic reduction in other regions.     

NLR、MPVLR、MPV在全膝关节置换术后急性下肢深静脉血栓形成诊断中的影响价值

摘要 目的：分析全膝关节置换术后急性下肢深静脉血栓（DVT）形成中NLR、MPVLR、MPV的临床诊断价值。方法：于本院2020年10月-2021年10月接受全膝关节置换术患者中筛选80例开展研究,纳入对象接受手术治疗后3到5日内接受彩色超声下肢DVT检查,依据检查证实是否发生下肢DVT作为分组标准,将结果证实发生下肢DVT患者43例纳入观察组,未发生的37例纳入对照组。两组同时接受血常规检查,汇总平均血小板体积（MPV）、淋巴细胞计数、中性粒细胞,并依据结果计算中性粒细胞/淋巴细胞计数（NLR）,平均血小板体积/淋巴细胞计数（MPVLR）,对患者临床资料展开回顾性分析,判断发生/未发生组别患者各项指标从差异,进而评价MPV、NLR、MPVLR对术后急性下肢DVT形成诊断的诊断价值。结果：发生下肢DVT与未发生下肢DVT患者,在性别、年龄、慢性病史（高血压、糖尿病）、吸烟史、体质量指数等方面,未见明显差异（P>0.05）。和未发生下肢DVT患者相比,发生下肢DVT患者中心粒细胞相对较低,淋巴细胞和血小板计数相对加高（P<0.05）。两组在白细胞上差异不大（P>0.05）。发生下肢DVT患者MPV、NLR、MPVLR明显高于未发生手术患者（P<0.05）;肿胀天数在7天及以上、高于7天患者在NLR指标上差异不大（P＞0.05）,而在MPVLR上组间有统计学差异（P<0.05）。结论：MPV、NLR、MPVLR指标对于判断全膝关节置换术治疗后判断是否发生急性下肢DVT具有较高诊断价值,其中MPVLR可作为下肢DVT早期诊断典型指标,为临床提供疾病判断依据,值得重视。     

Synthesis of a new C(2)-symmetric chiral catalyst and its application in the catalytic asymmetric borane reduction of prochiral ketones

A new C(2)-symmetric chiral catalyst 3,5-bis[(2S)-(hydroxy-diphenylmethyl)- pyrrolidin-1-ylmethyl]-1,3,4-oxadiazole was successfully synthesized by the reaction of 2,5-dichloromethyl-1,3,4-oxadiazole with (S)-alpha,alpha-diphenyl-2-pyrrolidinemethanol, and applied to the catalytic asymmetric reduction of prochiral ketones with borane. When the catalyst loading was 1 mol %, enantiomeric excesses of up to 86.8% and 94.5% were observed in reduction of aromatic and alpha-halo ketones, respectively.     

Influence of the ethanol and glucose supply rate on the rate and enantioselectivity of 3-oxo ester reduction by baker's yeast

Baker's-yeast-mediated reductions of ketones hold great potential for the industrial production of enantiopure alcohols. In this article we describe the stoichiometry and kinetics of asymmetric ketone reduction by cell suspensions of bakers' yeast (Saccharomyces cerevisiae). A system for quantitative analysis of 3-oxo ester reduction was developed and allowed construction of full mass and redox balances as well as determination of the influence of different process parameters on aerobic ketone reduction. The nature of the electron donor (ethanol or glucose) and its specific consumption rate by the biomass (0-1 mol.kg dw(-1).h(-1)) affected the overall stoichiometry and rate of the process and the final enantiomeric excess of the product. Excess glucose as the electron donor, i.e. a very high consumption rate of glucose, resulted in a high rate of alcoholic fermentation, oxygen consumption, and biomass formation and therefore causing low efficiency of glucose utilization. Controlled supply of the electron donor at the highest rates applied prevented alcoholic fermentation but still resulted in biomass formation and a high oxygen requirement, while low rates resulted in a more efficient use of the electron donor. Low supply rates of ethanol resulted in biomass decrease while low supply rates of glucose provided the most efficient strategy for electron donor provision and yielded a high enantiomeric excess of ethyl (S)-3-hydroxybutanoate. In contrast to batchwise conversions with excess glucose as the electron donor, this strategy prevented by-product formation and biomass increase, and resulted in a low oxygen requirement.     

A series of new C2-symmetric amino alcohols with multicoordination groups: promising catalysts for synthesis of both enantiomers in the borane-mediated reduction of prochiral ketones

A series of new C(2)-symmetric amino alcohols with multicoordination groups have been synthesized and successfully applied as catalysts in the borane asymmetric reduction of prochiral ketones in refluxing toluene, providing the corresponding secondary alcohols with up to 90% ee. An unusual temperature-dependent reversal of stereochemistry was also observed.     

重组基因工程菌在不对称还原羰基化合物中的应用

手性醇是药物合成的重要手性砌块,利用生物催化剂不对称还原羰基化合物是手性醇制备的重要方法。介绍了生物催化还原羰基化合物的反应原理及特点,综述了重组基因工程菌的构建及其在不对称还原羰基化合物中的应用情况,展望了今后研究发展的方向。     

Asymmetric catalysis by chiral lanthanide complexes in water

The development of catalytic, asymmetric transformations in water is a challenging task. The lanthanides are becoming reagents of choice for many Lewis acid-catalyzed reactions in aqueous media as they are water tolerant. However, enantioselective reactions catalyzed by lanthanides are difficult to achieve in water due to the instability of the reported catalysts. Herein we report the development of stable, well-defined chiral lanthanide complexes and their effectiveness in the asymmetric reduction of alpha-keto acids in aqueous solution. This is the first example of asymmetric reduction by a chiral lanthanide complex in water. Although modest ees are obtained (40-50%) the ytterbium complexes offer a unique advantage as they have the ability to monitor, direct from the reaction mixture, the % ee for the reaction, by 1H NMR, through a dipolar analysis of the observed paramagnetic shift.     

利用微生物重组技术促进羰基不对称还原研究进展

手性醇是许多手性药物合成的关键手性砌块,利用微生物细胞催化相应前手性羰基化合物不对称还原,是合成手性醇的重要方法之一。但应用野生微生物催化时,反应的时空产率、立体选择性较低。详细介绍了利用微生物重组技术以促进前手性羰基化合物不对称还原反应合成手性醇的国内外研究进展。从酶的种类、表达系统以及辅酶再生系统3个方面对重组细胞催化反应体系的构建进行了概述。同时按照反应底物的类型,对重组微生物在催化不同类型羰基化合物不对称还原合成手性醇中的应用分别进行了归纳和介绍。     

Debaryomyces hansenii as a new biocatalyst in the asymmetric reduction of substituted acetophenones

Chiral secondary alcohols are convenient mediator for the synthesis of biologically active compounds and natural products. In this study fifteen yeast strains belonging to three food originated yeast species Debaryomyces hansenii, Saccharomyces cerevisiae and Hanseniaspora guilliermondii were tested for their capability for the asymmetric reduction of acetophenone to 1-phenylethanol as biocatalyst microorganisms. Of these strains, Debaryomyces hansenii P1 strain showed an effective asymmetric reduction ability. Under optimized conditions, substituted acetophenones were converted to the corresponding optically active secondary alcohols in up to 99% enantiomeric excess and at high conversion rates. This is the first report on the enantioselective reduction of acetophenone by D. hansenii P1 from past?rma, a fermented Turkish meat product. The preparative scale asymmetric bio reduction of 3-methoxy acetophenone 1g by D. hansenii P1 gave (R)-1-(3-methoxyphenyl) ethanol 2g 82% yield, and >99% enantiomeric excess. Compound 2g can be used for the synthesis of (+)-NPS-R-568 [3-(2-chlorophenyl)-N-[(1R)-1-(3-methoxyphenly) ethyl] propan-1-amine] which have a great potential for the treatment of primary and secondary hyper-parathyroidism. In addition, D. hansenii P1 successfully reduced acetophenone derivatives. This study showed that this yeast can be used industrially to produce enantiomerically pure chiral secondary alcohols, which can be easily converted to different functional groups.     

Comparative characterization of novel ene‐reductases from cyanobacteria

The growing importance of biocatalysis in the syntheses of enantiopure molecules results from the benefits of enzymes regarding selectivity and specificity of the reaction and ecological issues of the process. Ene‐reductases (ERs) from the old yellow enzyme family have received much attention in the last years. These flavo‐enzymes catalyze the trans‐specific reduction of activated C?C bonds, which is an important reaction in asymmetric synthesis, because up to two stereogenic centers can be created in one reaction. However, limitations of ERs described in the literature such as their moderate catalytic activity and their strong preference for NADPH promote the search for novel ERs with improved properties. In this study, we characterized nine novel ERs from cyanobacterial strains belonging to different taxonomic orders and habitats. ERs were identified with activities towards a broad spectrum of alkenes. The reduction of maleimide was catalyzed with activities of up to 35.5 U mg^?1 using NADPH. Ketoisophorone and (R)‐carvone, which were converted to the highly valuable compounds (R)‐levodione and (2R,5R)‐dihydrocarvone, were reduced with reaction rates of up to 2.2 U mg^?1 with NADPH. In contrast to other homologous ERs from the literature, NADH was accepted at moderate to high rates as well: Enzyme activities of up to 16.7 U mg^?1 were obtained for maleimide and up to 1.3 U mg^?1 for ketoisophorone and (R)‐carvone. Additionally, excellent stereoselectivities were achieved in the reduction of (R)‐carvone (97–99% de). In particular, AnabaenaER3 from Anabaena variabilis ATCC 29413 and AcaryoER1 from Acaryochloris marina MBIC 11017 were identified as useful biocatalysts. Therefore, novel ERs from cyanobacteria with high catalytic efficiency were added to the toolbox for the asymmetric reduction of alkenes. Biotechnol. Bioeng. 2013; 110: 1293–1301. © 2012 Wiley Periodicals, Inc.     

Quantitative characterization of virus-like particles by asymmetrical flow field flow fractionation, electrospray differential mobility analysis, and transmission electron microscopy

Here we characterize virus-like particles (VLPs) by three very distinct, orthogonal, and quantitative techniques: electrospray differential mobility analysis (ES-DMA), asymmetric flow field-flow fractionation with multi-angle light scattering detection (AFFFF-MALS) and transmission electron microscopy (TEM). VLPs are biomolecular particles assembled from viral proteins with applications ranging from synthetic vaccines to vectors for delivery of gene and drug therapies. VLPs may have polydispersed, multimodal size distributions, where the size distribution can be altered by subtle changes in the production process. These three techniques detect subtle size differences in VLPs derived from the non-enveloped murine polyomavirus (MPV) following: (i) functionalization of the surface of VLPs with an influenza viral peptide fragment; (ii) packaging of foreign protein internally within the VLPs; and (iii) packaging of genomic DNA internally within the VLPs. These results demonstrate that ES-DMA and AFFFF-MALS are able to quantitatively determine VLP size distributions with greater rapidity and statistical significance than TEM, providing useful technologies for product development and process analytics.     

马克斯克鲁维酵母羰基还原酶基因的克隆与表达

【目的】研究羰基还原酶基因的克隆、表达及其在不对称生物催化中的应用。【方法】对羰基还原酶氨基酸序列进行BLAST推导出核苷酸序列,设计引物,以马克斯克鲁维酵母(Kluyveromyce marxianus)CGMCC 2.1977全基因组为模板,通过PCR扩增目的片段,与载体pET-28a连接,转化大肠杆菌获得重组菌BL21(DE3)-(pET28a-cMCR)和Rosetta(DE3)-(pET28a-cMCR)。【结果】扩增的序列与已报道的mer序列有100%同源性,全长1 038 bp,共编码345个氨基酸。目的蛋白在Rosetta(DE3)-(pET28a-cMCR)得到了高效表达,大小为42 kD。该酶最适反应温度为40°C,最适反应pH是8,热稳定性与pH稳定性较差。Ca2+对酶活具有明显的激活作用,且浓度为0.5 mmol/L时效果最好。重组菌可还原4-氯乙酰乙酸乙酯(COBE)为(S)-4-氯-3-羟基丁酸乙酯[(S)-CHBE],光学纯度为100%,转化率为81.0%。重组菌在制备度洛西汀关键中间体(S)-氮,氮-二甲基-3-羟基-(2-噻吩)-l-丙胺[(S)-DHTP]中也得到初步应用。【结论】从菌株马克斯克鲁维酵母(Kluyveromyce marxianus)CGMCC 2.1977中克隆获得了羰基还原酶基因,在大肠杆菌中成功表达,并可应用于不对称还原。     

One-Electron Reduction of Daunorubicin Intercalated in DNA or in A Protein : A Radiolysis Study

The one-electron reduction of daunorubicin, an anthracycline antibiotic, intercalated in DNA or in the apoprotein of the riboflavin binding protein, was studied by $ radiolysis. The two reduction mechanisms appear very similar to the one found for the non-intercalated drug. Hydrogen peroxide, which oxidizes non-intercalated hydroquinone daunorubicin with two electrons in one step (C. Houée-Levin, M. Gardès-Albert and C. Ferradin, FEBS leu. 173 27-30, (1984)), reacts with daunorubicin hydroquinone in DNA but not in the protein. It appears thus that the site accessibility to hydrogen peroxide in DNA is better than in the protein. Biological consquences are discussed.     

X-ray dose reduction using additional copper filtration for abdominal digital radiography: Evaluation using signal difference-to-noise ratio

PurposeX-ray dose reduction using additional copper filters (Cu-filters) for abdominal general radiography was indicated in a report using a simulation study. We validated the dose reduction effects using a clinical digital radiography system equipped with an indirect-type CsI detector and an automatic Cu-filter insertion function.MethodsThe image qualities were evaluated using signal difference-to-noise ratio (SDNR) for different radiation qualities with and without Cu-filters for a 20-cm acrylic phantom. Acrylic and bone equivalent material plates were used for contrast measurements. The dose reduction using Cu-filters was estimated from the ratios of the SDNR² values.ResultsFor the same entrance surface dose (ESD), Cu-filters with 0.1- and 0.2-mm thicknesses increased the image quality as evaluated by SDNR² and the estimated dose reduction without degrading the image quality. For the acrylic contrast, the dose reductions with the 0.1- and 0.2-mm-thick Cu-filters were approximately 30% and 44% at 70 kV and 29% and 35% at 80 kV, respectively. For the bone contrast, the reduction rates were slightly reduced.ConclusionsWe validated the dose reduction capability of additional Cu-filters without degrading the image quality for abdominal radiography. The estimated entrance surface dose reductions of the Cu-filters were approximately 30–40% and 20–30% for the acrylic and bone contrasts, respectively, and effective dose reductions for acrylic were nearly half of those for ESD. At these reduced dose conditions, the current time product values needed to be increased by factors of 1.4 and 1.8 for the 0.1- and 0.2-mm-thick Cu-filters, respectively.     

Management strategies for controlling endemic and seasonal mouse parvovirus infection in a barrier facility

Despite improved diagnostic and rederivation capabilities, research facilities still struggle to manage parvovirus infections (e.g., mouse parvovirus (MPV) and minute virus of mice) in mouse colonies. Multi-faceted approaches are needed to prevent adventitious organisms such as MPV from breaching a barrier facility. In this article, the authors document recent changes to the Salk Institute's animal care program that were intended to help manage mouse parvovirus in the barrier facility. Specifically, the Institute started to use a new disinfectant and to give mice irradiated feed. The authors found an association between these modifications and a reduction in MPV incidence and prevalence in endemically infected colonies. These data suggest that using irradiated feed and appropriate disinfectants with contemporary management practices can be an effective plan for eradicating or controlling MPV infection in a research facility. The authors recommend further study of the environmental risk factors for parvovirus infection and of potential biological interactions associated with the use of irradiated feed.     

Enantioselective reduction of ketones with borane catalyzed by tridentate amino alcohols derived from salicylaldehyde

In the presence of tridentate chiral ligand 4e, 99% e.e. value was obtained by asymmetric reduction of ethyl benzoylacetate with borane in toluene at 25 degrees C. Various ligands and reaction conditions were investigated to develop a reasonable mechanism that explains the experimental outcomes.