Eicosapentaenoic acid代谢产物促进胰岛α细胞转分化为胰岛β细胞的作用研究

目的 探讨eicosapentaenoic acid(EPA)代谢产物促进胰岛α细胞向β细胞转分化的作用。方法 雄性C57BL/6J小鼠连续5 d腹腔注射60 mg/kg链脲佐霉素(streptozocin, STZ)构建1型糖尿病(T1DM)小鼠模型,2周后随机分为模型组、97%EPA饮食干预组、75%鱼油(50%EPA+25%DHA)饮食干预组,每周检测随机血糖;模型到期后,通过免疫荧光染色观察小鼠胰腺中胰岛β细胞再生情况。提取tdTomato荧光蛋白特意标记α细胞的小鼠(GCGicre小鼠与Rosa26tdTomato小鼠杂交获得)胰岛,加入1 mmol·L^(-1)STZ诱导β细胞凋亡,添加EPA代谢产物,培养48 h后,利用荧光染色观察胰岛素和tdTomato荧光的表达。在小鼠胰岛α细胞系αTC1培养基中添加EPA代谢产物,48 h后,利用荧光染色观察胰岛素和胰高血糖素的表达。结果 EPA和鱼油饮食干预均可明显降低T1DM小鼠的血糖水平,改善葡萄糖稳态,且胰腺中出现胰岛素和胰高血糖素共定位细胞;EPA代谢产物引起已发生β细胞凋亡的小鼠胰岛中发生tdTomato荧光蛋白和胰岛素共定位;EPA代谢产物可促进胰岛αTC1细胞系细胞分泌胰岛素。结论 EPA及其代谢产物可通过促进胰岛α细胞转分化为β细胞,进而增加胰岛素的分泌,缓解T1DM小鼠的高血糖症状。

Continuous-flow electrosynthesis of urea and oxalic acid by CO_(2)-nitrate reduction and glycerol oxidation

Urea and oxalic acid are critical component in various chemical manufacturing industries.However,achieving simultaneous generation of urea and oxalic acid in a continuous-flow electrolyzer is a challenge.Herein,we report a continuous-flow electrolyzer equipped with 9-square centime-ter-effective area gas diffusion electrodes(GDE)which can simultaneously catalyze the glycerol oxidation reaction in the anode region and the reduction reaction of CO_(2) and nitrate in the cathode region,producing oxalic acid and urea at both the anode and cathode,respectively.The current density at low cell voltage(0.9 V)remained above 18.7 mA cm^(-2) for 10 consecutive electrolysis cycles(120 h in total),and the Faraday efficiency of oxalic acid(67.1%) and urea(70.9%)did not decay.Experimental and theoretical studies show that in terms of the formation of C-N bond at the cathode,Pd-sites can provide protons for the hydrogenation process of CO_(2) and NO_(3)^(-),Cu-sites can promote the generation of *COOH and Bi-sites can stabilize *COOH.In addition,in terms of glycerol oxidation,the introduction of Cu and Bi into Pd metallene promotes the oxidation of hydroxyl groups and the cleavage of C-C bond in glycerol molecules,respectively.

Humic Acid Effects on Reducing Corn Leaf Burn Caused by Foliar Spray of Urea-Ammonium Nitrate at Different Humic Acid/Urea-Ammonium Nitrate Ratios

Technologies for reducing corn leaf burn caused by foliar spray of urea-ammonium nitrate (UAN) during the early growing season are limited. A field experiment was carried out to evaluate the effects of humic acid on corn leaf burn caused by foliar spray of undiluted UAN solution on corn canopy at Jackson, TN in 2018. Thirteen treatments of the mixtures of UAN and humic acid were evaluated at V6 of corn with different UAN application rates and different UAN/humic acid ratios. Leaf burn during 1 2, 3, 4, 5, 6, 7, and 14 days after UAN foliar spray significantly differed between with or without humic acid addition. The addition of humic acid to UAN significantly reduced leaf burn at each UAN application rate (15, 25, and 35 gal/acre). The reduction of leaf burn was enhanced as the humic acid/UAN ratio went up from 10% to 30%. Leaf burn due to foliar application of UAN became severer with higher UAN rates. The linear regression of leaf burn 14 days after application with humic acid/UAN ratio was highly significant and negative. However, the linear regression of leaf burn 14 days after application with the UAN application rate was highly significant and positive. In conclusion, adding humic acid to foliar-applied UAN is beneficial for reducing corn leaf burn during the early growing season.

Cys C、C1q、β_(2)-MG、Urea、UA检测对初诊多发性骨髓瘤患者合并肾损伤的诊断价值

目的探讨肾功能指标胱抑素C(cystatin C,Cys C)、补体C1q(complement C1q)、β_(2)-微球蛋白(β_(2)-microglobulin,β_(2)-MG)、尿素(Urea)、尿酸(uric acid,UA)对初诊多发性骨髓瘤(multiplemyeloma,MM)患者合并肾损伤(renal impairment,RI)的诊断价值。方法回顾性分析2021年8月~2022年12月首都医科大学附属北京积水潭医院血液科收治的93例初诊MM患者的病例资料,按照血肌酐水平将MM患者分为RI组[血肌酐>176.80mmol/L(2mg/dl),n=19]及非RI组[血肌酐≤176.80mmol/L(2mg/dl),n=74],对RI组和非RI组的临床资料及实验室指标进行分析。采用单因素和多因素Logistic回归分析评价MM患者发生RI的危险因素,应用受试者工作特征(receiver operating characteristic,ROC)曲线评估危险因素对MM患者发生RI的预测价值。结果93例初诊MM患者发生RI者占25.68%,RI组轻链型占比最高(36.84%,7/19),IgG-λ型和IgA-κ型比例最低(10.53%,2/19);非RI组IgA-κ型比例最高(29.73%,22/74),IgG-λ型比例最低(12.16%,9/74)。DS分期中,RI组19例全部为Ⅲ期,非RI组72例全部为Ⅲ期。ISS分期中,RI组Ⅲ期最多(68.42%,13/19),非RI组中Ⅰ期最多(41.89%,31/74)。RISS分期中,RI组Ⅱ期和Ⅲ期最多(36.84%,7/19),非RI组Ⅱ期最多(58.11%,43/74)。DS分期和ISS分期组间差异有统计学意义(P<0.05)。RI组中Cys C、β_(2)-MG、Urea、UA水平均高于非RI组,差异均有统计学意义(P<0.05)。单因素分析结果显示,Cys C、Urea、β_(2)-MG水平异常升高是MM患者发生RI的危险因素(P<0.05),C1q对MM患者发生RI没有影响(P>0.05);多因素Logistic回归分析结果显示,Cys C、Urea、β_(2)-MG水平异常升高均是MM患者发生RI的独立影响因素(P<0.05)。Cys C、Urea、β_(2)-MG预测MM患者发生RI的敏感度分别为88.9%、50.0%、94.4%,特异性分别为90.4%、100.0%、84.9%;Cys C、Urea、β_(2)-MG联合检测预测MM患者发生RI的敏感度为100.0%,特异性为87.7%。结论Cys C、Urea、β_(2)-MG均能较好地预测初诊MM患者发生RI的可能性,3项指标联合检测对MM患者发生RI具有更高的预测价值。

Effects of Nutritional Factors on the Growth and Heterotrophic Eicosapentaenoic Acid Production of Diatom Nitzschia laevis

The effects of several nutritional factors on the growth and eicosapentaenoic acid （EPA） production of diatom Nitzschia laevis were studied. 4LDM （quadrupled concentration of the nutrient salt） was the optimal concentration of nutrient salt for the growth and EPA production ofN. laevis. The growth ofN. laevis was inhibited when the glucose concentration was either lower than 10gL^-1 or higher than 15 gL^-1. Both sodium nitrate and urea were good nitrogen sources for the growth and EPA production, while ammonium chloride seriously decreased the dry cell weight （DW） and the EPA content. Silicate seriously influenced the growth of N. laevis. The maximum DW of 2.34 gL^-1 was obtained in the presence of 150 mgL^-1 Na2SiO3· 9H2O. The EPA content remained almost the same when the silicate concentration was lower than 150mgL^-1; however, higher silicate concentrations resulted in a steady decrease of EPA content. Low medium salinity （≤29） did not seem to influence the DW of N. laevis, and high salinity resulted in a decrease of DW. The highest EPA content （4.08%） and yield （110mgL^-1） were observed at the salinity of 36 and 29, respectively. Key words polyunsaturated fatty acid; eicosapentaenoic acid; microalga; Nitzschia laevis; heterotrophy

Enrichment of nervonic acid in Acer truncatum Bunge oil by combination of two-stage molecular distillation,one-stage urea complexation and five-stage solvent crystallization

Nervonic acid is the world’s first and only potent substance that can repair damaged nerve fibers and promote nerve cell regeneration with high nutritional value.The wide variety of fatty acids in plant oils and fats with similar structures makes the large-scale separation and purification of high-purity nervonic acid very difficult.A new combined process of molecular distillation,urea inclusion and solvent crystallization was established to prepare high-purity nervonic acid with the mixed fatty acids obtained after saponification and acidification of Acer truncatum Bunge oil as raw materials.First,according to the difference in the mean free path of fatty acids,molecular distillation was used to separate and remove C16 saturated fatty acid of palmitic acid and four C18-C20 fatty acids of stearic,oleic,linoleic,and linolenic acids.The content of C16-C20 fatty acids decreased from 72.92% to 19.22% after two-stage molecular distillation processes,in which the contents of saturated fatty acid of palmitic acid decreased to about 0.5%.Then,according to the difference in carbon chain length and saturation of fatty acid,the contents of C22-C24 saturated fatty acids of tetracosanoic and docosanoic acids decreased to 0.21% and 0.07% by urea inclusion with urea/free fatty acid preparation by saponification(SPOMFs)ratio as 0.6.In addition,all saturated fatty acids were basically separated.Finally,according to the difference in the solubility of fatty acids in solvents,the C18-C20 unsaturated fatty acids of oleic,linoleic,and linolenic acids and C22 unsaturated fatty acid of erucic acid were removed by solvent crystallization.The content of C18-C20 unsaturated fatty acids decreased to less than 5% with pentanol as the solvent after the first stage solvent crystallization.The content of erucic acid decreased to 3.47% with anhydrous ethanol as the solvent after the second to fifth stage solvent crystallization.The combined process of molecular distillation,urea inclusion and low temperature crystallization innovatively adopted an efficient,simple and easy-toindustrial solvent crystallization method to separate erucic and nervonic acids,obtaining nervonic acid with purity of 96.53% and final yield of 47.99%.

Research on Arachidonic Acid and Eicosapentaenoic Acid Anabolic Metabolism in Diasporangium sp.

The fatty acids of a strain of Diasporangium sp.had been analyzed by using GC-MS.The fatty acids of twenty mutants were determined.Based on these results,the producing of eicosapentaenoic acid(EPA)supposed via 18∶2,18∶3,20∶3,20∶4 which all belong to ω-6 fatty acids.The ω-3 desaturation was undertaken at arachidonic acid(AA).In addition,mutant strains resulted in enhanced content of AA which could get two times more than initial strain,but no compact on EPA.

Fatty Acid Composition and Digestive Enzyme Activities of Rainbow Trout in Response to Dietary Docosahexaenoic Acid(DHA)and Eicosapentaenoic Acid(EPA)During Salinity Acclimation

This physiological study aimed to evaluate the effects of dietary docosahexaenoic acid(DHA)and eicosapentaenoic acid(EPA)on the fatty acid composition and digestive enzyme activities of rainbow trout(Oncorhynchus mykiss)during salinity acclimation.Rainbow trout with an average initial weight of 90.61 g±9.25 g were fed diets with the quantities of DHA and EPA equaling to 0.54%,0.95%,1.40%and 1.79%(abbreviated as DE-0.54,DE-0.95,DE-1.40,and DE-1.79,respectively)for eight weeks,after which the gastric and intestinal fatty acids composition were analyzed.Subsequently,the fish underwent salinity acclimation.On days 1,4,7,and 14 after the freshwater was replaced by seawater and at the end of the 8-week period,gastric and intestinal digestive enzyme activities were determined.The results showed that the gastric and intestinal DHA and EPA contents of the fish were positively correlated to their dietary DHA and EPA levels.Low dietary DHA and EPA levels inhibited the protease activity of rainbow trout.Fish in the DE-0.54 group increased the lipase activity to enhance the utilization of lipids maybe due to the inadequate essential fatty acids for fish in this group.Hence,rainbow trout in the DE-0.54 group failed to maintain suitable activities of digestive enzymes after salinity acclimation.Therefore,a diet with minimum 0.95%DHA and EPA levels is necessary for rainbow trout during salinity acclimation.

Fatty Acid Treatment with Pure Omega-3 Eicosapentaenoic Acid Ethyl Ester for Patients with Cardiovascular Diseases: Differences between Branded (EPADEL®) and Generic Products

Background: Omega-3 polyunsaturated fatty acids (PUFAs) have some protective benefits for patients with coronary artery and cerebrovascular diseases. Eicosapentaenoic acid (EPA) drugs are prescribed as branded (B: EPADEL?) or generic products but no data exist concerning the differences in treatment outcomes between these products. Methods and Results: We investigated the differences in the serum levels of EPA, docosahexaenoic acid (DHA) and arachidonic acid (AA), and the EPA/AA ratios through blood sampling six months after daily administration of 1800 mg of EPADEL? and a generic EPA drug was initiated for 96 patients with cardiovascular diseases. All patients received these PUFA treatments while continuing with baseline therapy. After 6 months of administration, EPADEL? produced better results than the generic (G) product (EPA;baseline: 59.4 ± 25.5 μg, B: 215.5 ± 58.8 μg, G: 199.7 ± 63.8 μg, B vs G, p < 0.0005;AA;baseline: 197.4 ± 44.6 μg, B: 158.3 ± 36.3 μg, G: 163.6 ± 38.9 μg, B vs G, p < 0.02, as mean ± SD). Conclusions: There were clear differences between EPA branded and the generic products. Further study is required to determine whether the benefits from the branded product justify the higher price compared to the generic drug cost.

Effect of eicosapentaenoic acid on regional arterial stiffness:Assessment by tissue Doppler imaging

AIM: To evaluate the effects of eicosapentaenoic acid (EPA) on regional arterial stiffness assessed by strain rate using tissue Doppler imaging. METHODS: Nineteen eligible patients were prospectively studied (mean age 62 ± 8 years, 68% men). Subjects with large vessel complications and/or diabetes mellitus were excluded. The strain rate of the ascending aorta was measured by tissue Doppler imaging as an index of regional arterial stiffness, and brachial-ankle pulse wave velocity (baPWV) was measured as an index of degree of systemic arteriosclerosis. These indices were compared before and after administration of EPA at 1800 mg/d for one year. RESULTS: The plasma concentration of EPA increased significantly after EPA administration (3.0% ± 1.1% to 8.5% ± 2.9%, P < 0.001). There were no significant changes in baPWV (1765 ± 335 cm/s to 1745 ± 374 cm/s), low-density lipoprotein cholesterol levels (114 ± 29 mg/dL to 108 ± 28 mg/dL), or systolic blood pressure (131 ± 16 mmHg to 130 ± 13 mmHg) before and after EPA administration. In contrast, the strain rate was significantly increased by administration of EPA (19.2 ± 5.6 s-1, 23.0 ± 6.6 s-1, P < 0.05). CONCLUSION: One year of administration of EPA resulted in an improvement in regional arterial stiffness which was independent of blood pressure or serum cholesterol levels.

Solid Dose Form of Metformin with Ethyl Eicosapentaenoic Acid Does Not Improve Metformin Plasma Availability

Background: The purpose of the study was to investigate effects of ethyl eicosapentaenoic acid on pharmacokinetics of metformin. Pharmacokinetic profiles of metformin and ethyl eicosapentaenoic acid when delivered separately or together in solid dose form were investigated and compared to determine whether the solid dose resulted in an altered metforminpharmacokinetics when given with or without food. Methods: A single-center, open-label, repeated dose study investigated the pharmacokinetic (PK) profile of metformin when administered in solid dose form with ethyl eicosapentaenoic acid compared to co-administration with icosapent ethyl, an ester of eicosapentaenoic acid and ethyl alcohol used to treat severe hypertriglyceridemia with metformin hydrochloride. Non-compartmental PK methods were used to compare area under the plasma concentration curve (AUC) and maximum plasma concentration (Cmax) between patients randomized to either the ester or separate medications group under both fasting and fed conditions. Results: Using these two PK parameters, results showed that metformin availability was higher under fasting conditions when delivered separately from icosapent ethyl. There were no group differences in the fed condition. Conclusions: The solid dose form of metformin and ethyl eicosapentaenoic acid did not improve the pharmacokinetics of metformin in terms of plasma availability, suggesting that little is to be gained over the separate administration of ethyl eicosapentaenoic acid and metformin hydrochloride.

Preparation of High-Purity Linolenic Acid from Oil of Lithospermum Erythrorhizon by Urea Inclusion and Column Chromatography

Aim To separate high purity linolenic acid from the oil of Lithospermumerythrorhizon growing in the Northeast of China. Methods Urea inclusion and column chromatographywere used. Results Unsaturated fatty acid was separated, with a purity of 99.30 wt% of linolenicacid. Conclusion The experiment shows excellent reproducibility and high feasibility for industrialproduction.

Concentration of α-Linoleic Acid of Perilla Oil by Gradient Cooling Urea Inclusion

In this study, production of ct-linoleic acid concentrated from crude perilla oil by gradient cooling urea inclusion was optimized. The fatty acid composition was determined after ethyl esterification by gas chromatography （GC）. In this process, orthogonal experiment was carried out. Under optimum conditions, the maximum amount of α-linoleic acid （91.5%） was obtained at a urea to fatty acid ratio of 3, a solvent to fatty acids ratio of 7, a reaction temperature of 348 K and a crystallization time of 690 min. A simple method of gradient cooling urea inclusion was used to purify α-linolenic acid by using urea to form inclusion complexes with the saturated and the less unsaturated fatty acids, which enhanced the purity of α-linoleic acid ethyl ester by above 90%.

Effects of urea enhanced with different weathered coal-derived humic acid components on maize yield and fate of fertilizer nitrogen

Humic acid(HA) is a readily available and low-cost material that is used to enhance crop production and reduce nitrogen(N) loss. However, there is little consensus on the efficacy of different HA components. In the current study, a soil column experiment was conducted using the ^(15)N tracer technique in Dezhou City, Shandong Province, China, to compare the effects of urea with and without the addition of weathered coal-derived HA components on maize yield and the fate of fertilizerderived N(fertilizer N). The HA components were incorporated into urea by blending different HA components into molten urea to obtain the three different types of HA-enhanced urea(HAU). At harvest, the aboveground dry biomass of plants grown with HAU was enhanced by 11.50–21.33% when compared to that of plants grown with U. More significantly, the grain yields under the HAU treatments were 5.58–18.67% higher than the yield under the urea treatment. These higher yields were due to an increase in the number of kernels per plant rather than the weight of individual kernels. The uptake of fertilizer N under the HAU treatments was also higher than that under the urea treatment by 11.49–29.46%, while the unaccounted N loss decreased by 12.37–30.05%. More fertilizer-derived N was retained in the 0–30 cm soil layer under the HAU treatments than that under the urea treatment, while less N was retained in the 30–90 cm soil layer. The total residual amount of fertilizer N in the soil column, however, did not differ significantly between the treatments. Of the three HAU treatments investigated, the one with an HA fraction derived from extraction with pH values ranging from 6 to 7, resulted in the best improvement in all assessment targets. This is likely due to the abundance of the COO/C–N=O group in this HA component.

Effect of Combined Application of Humic Acid and Urea on the Wheat Growth and Yield

This paper aims to research the effects of combined application of humic acid and urea on the wheat yield and yield component,and establish rational fertilizer application scheme of wheat. Split plot experiment was adopted. Two types of phosphorus fertilizer( adding humic acid or not) was assigned to the main plot,and four types of top dressing modes( different amount of urea and humic acid urea) were used in subplots. Effects of combined application of humic acid and urea on the wheat yield and yield component were researched. 375 kg / ha ordinary DAP + 150 kg / ha urea was used as base fertilizer; topdressing of 300 kg / ha urea humate could effectively promote the plant height,leaf area coefficient and aboveground dry matter amount. Adding humic acid in urea in topdressing significantly enhanced the wheat yield and economic coefficient of wheat. Adding humic acid in urea in topdressing has better effects of yield increasing than base fertilizer,and can be used for large scale extension.

Synthesis and Antibacterial Activity of Urea and Thiourea Derivatives of Anacardic Acid Mixture Isolated from A Natural Product Cashew Nut Shell Liquid (CNSL)

Synthesis and antibacterial activity of some novel urea and thiourea derivatives (8a - 8k, 9a - 9f) of anacardic acid prepared from commercially available anacardic acid which is obtained from natural product Cashew Nut Shell Liquid (CNSL). Compounds (8a - 8k, 9a - 9f) were tested for Gram positive and Gram negative bacterial cultures. Most of the compounds were showed active compared with standard drug ampicilline.

Optical nonlinearity in measurement of urea and uric acid in blood

The Z-scan technique is a simple and effective tool for determining nonlinear optical properties of materials. This technique is utilized in meas-urement of urea and uric acid in blood. The nonlinear refractive index of urea and uric acid are found to vary linearly with concentration. Hence by calculating the nonlinear refractive index it is possible to measure their concentra-tion in the sample. The results of this method are found to be in good agreement with the conventional colorimetric method.

The Synthesis and Anion Binding of Novel Cholic Acid-based Molecular Clefts Containing Unsymmetrically Disubstituted Urea Unit

A novel type of chiral molecular clefts consisting of a rigid deoxycholic acid methyl ester backbone and chiral unsymmetrically disubstituted urea side chain have been designed and synthesized. All these new receptors 3a^c and the corresponding key intermediates 1a^c and 2a^c are new compounds, their structures were confirmed by 1HNMR, IR, MS spectra and elemental analysis. These molecular clefts showed binding ability for halide anions.

Synthesis and Antibacterial Activity of Urea and hiourea Derivatives at C-8 Alkyl Chain of Anacardic Acid Mixture Isolated from a Natural Product Cashew Nut Shell Liquid (CNSL)

Synthesis and antibacterial activity of some novel urea and thiourea derivatives (7a-7k, 8a-8f) of anacardic acid prepared from commercially available anacardic acid which is obtained from natural product Cashew Nut Shell Liquid (CNSL). Compounds (7a-7k, 8a-8f) were tested for Gram positive and Gram negative bac- terial cultures. Most of the compounds were showed active compared with standard drug ampicilline.

Density Functional Theory Study of Infrared and Ultraviolet Spectra of Urea L-Malic Acid

Urea L-malic acid, a new second order nonlinear optical crystal, was studied using density functional theory （DFT）. PBEPBE/6-31＋G（d,p） method, the optimal method for comparing the results from the several DFT methods, was chosen to study the molecular structure. Infrared and ultraviolet-visible spectra were obtained and compared with experiments. The ultraviolet-visible spectrum was also analyzed by the molecular orbital population. The geometries, and the infrared and ultraviolet-visible spectra in water were studied using DFT methods in combination with the polarized continuum model to predict the perturbations by the solvent effect.