确定性需求下的最优保理融资与生产策略

企业为下游买方提供赊销,由于大量的资金被应收账款占用,企业可能因资金不足而无法生产足够的产品。企业可以通过保理(出售应收账款)进行融资,减小需求损失。在离散时间多周期的确定需求下,使用决策变量描述各周期的系统状态及其状态转移方程,将此问题建模为线性规划。通过分析此问题的结构特点,再提出了一种新颖且等价的建模方法,可以有效减少决策变量和约束条件的数量。在连续时间模型和混合模型中,这种建模方法同样适用,将优化问题写为连续线性规划,极大地降低了优化问题的复杂度。此连续线性规划问题可通过适当的区间划分进行离散化,用分片常量函数代替优化模型中的一般函数(无限维)决策变量,通过求解有限维线性规划得到原问题的可行近似解。最后,通过数值例子分析了贴现率对企业利润的影响。     

Zinc and Copper Ions Induce Aggregation of Human β-Crystallins

Cataracts are defined as the clouding of the lens due to the formation of insoluble protein aggregates. Metal ions exposure has been recognized as a risk factor in the cataract formation process. The γ and β crystallins are members of a larger family and share several structural features. Several studies have shown that copper and zinc ions induce the formation of γ-crystallins aggregates. However, the interaction of metal ions with β-crystallins, some of the most abundant crystallins in the lens, has not been explored until now. Here, we evaluate the effect of Cu(II) and Zn(II) ions on the aggregation of HβA1, as a representative of the acidic form, and HβB2, as a representative of the basic β-crystallins. We used several biophysical techniques and computational methods to show that Cu(II) and Zn(II) induce aggregation following different pathways. Both metal ions destabilize the proteins and impact protein folding. Copper induced a small conformational change in HβA1, leading to high-molecular-weight light-scattering aggregates, while zinc is more aggressive towards HβB2 and induces a larger conformational change. Our work provides information on the mechanisms of metal-induced aggregation of β-crystallins.     

Wheat Germ Spermidine and Clove Eugenol in Combination Stimulate Autophagy In Vitro Showing Potential in Supporting the Immune System against Viral Infections

Impaired autophagy, responsible for increased inflammation, constitutes a risk factor for the more severe COVID-19 outcomes. Spermidine (SPD) is a known autophagy modulator and supplementation for COVID-19 risk groups (including the elderly) is recommended. However, information on the modulatory effects of eugenol (EUG) is scarce. Therefore, the effects of SPD and EUG, both singularly and in combination, on autophagy were investigated using different cell lines (HBEpiC, SHSY5Y, HUVEC, Caco-2, L929 and U937). SPD (0.3 mM), EUG (0.2 mM) and 0.3 mM SPD + 0.2 mM EUG, significantly increased autophagy using the hallmark measure of LC3-II protein accumulation in the cell lines without cytotoxic effects. Using Caco-2 cells as a model, several crucial autophagy proteins were upregulated at all stages of autophagic flux in response to the treatments. This effect was verified by the activation/differentiation and migration of U937 monocytes in a three-dimensional reconstituted intestinal model (Caco-2, L929 and U937 cells). Comparable benefits of SPD, EUG and SPD + EUG in inducing autophagy were shown by the protection of Caco-2 and L929 cells against lipopolysaccharide-induced inflammation. SPD + EUG is an innovative dual therapy capable of stimulating autophagy and reducing inflammation in vitro and could show promise for COVID-19 risk groups.     

Antiproliferative and Pro-Apoptotic Effects of a Phenolic-Rich Extract from Lycium barbarum Fruits on Human Papillomavirus (HPV) 16-Positive Head Cancer Cell Lines

The in vitro antiproliferative activity of a phenolic-rich extract from Lycium barbarum fruits against head and neck HPV16 squamous cell carcinoma (OSCC) has been demonstrated, indicating for the first time that L. barbarum extract inhibits human papillomavirus (HPV) type 16 cell lines. Ethanol extract of L. barbarum was used for cell viability evaluation on SCC090, CAL27, and HGnF cell lines. After 24 and 48 h, the cell cycle effect of L. barbarum extract (at 1.0, 10, and 100 µg/mL) was measured via flow cytometry. In addition, the mRNA expression on E6/E7 and p53 via RT-PCR and the expression of p16, p53, Ki-67, and Bcl-2 via immunohistochemistry were also determined. Untreated cells, 20 µM cisplatin, and a Camellia sinensis-derived extract were used as negative and positive controls, respectively. We demonstrated that the studied L. barbarum extract resulted in G₀/G₁ arrest and S phase accumulation in SCC090 at 1.0 and 10 μg/mL. A reduction in mRNA levels of E6/E7 oncogenes (p < 0.05) with p53 overexpression was also observed through PCR, while immunohistochemical analyses indicated p16 overexpression (p > 0.05) and a decrease in p53 overexpression. The observed effects were associated with anticancer and immunomodulatory phenolics, such as flavonols/flavan-3-ols and tyramine-conjugated hydroxycinnamic acid amides, identified in the studied extract. These findings revealed that the phenolic-rich extract of L. barbarum fruits has promising properties to be considered further for developing new therapies against oral and oropharyngeal HPV lesions.     

盐酸洛美沙星与人血清白蛋白相互作用的荧光光谱

应用荧光光谱法研究了生理条件下盐酸洛美沙星(LOM)与人血清白蛋白(HSA)相互作用机制。研究表明:盐酸洛美沙星对HSA内源荧光的猝灭机制属于形成复合物所引起的静态猝灭,猝灭速率常数Kq为3.37×1012L.mol-1.S-1;结合常数为1.23×105,结合位点数为1.11,并根据F rster非辐射能量转移理论,计算出盐酸洛美沙星与HSA相互结合时其供体-受体间的结合距离(R=2.44 nm)和能量转移效率(E=0.209)。通过HSA与抗菌药物盐酸洛美沙星结合反应,探讨了药物盐酸洛美沙星在生物体内与蛋白质相互作用的生物学效应及其作用机理,讨论了共存Cu2+、Fe3+、Zn2+对盐酸洛美沙星与HSA结合反应的影响。     

Rapid and sensitive determination of levofloxacin in microsamples of human plasma by high‐performance liquid chromatography and its application in a pharmacokinetic study

A rapid, sensitive and simple high‐performance liquid chromatographic assay with ultraviolet detection was developed for the quantification of levofloxacin in microsamples (100 μL) of human plasma. The extraction procedure included a protein precipitation technique and a short chromatographic running time (4.5 min). Analyses were carried out on a Symmetry C₁₈ column using a mixture of acetonitrile and 0.01 m potassium dihydrogen aqueous solution (pH 3.4; 14:86 v/v) as mobile phase. The method provided specificity and was linear (r ≥ 0.9992) over the concentration range 0.1–12 µg/mL. The average absolute recovery was 93.59%. The intra‐ and inter‐day coefficients of variation were <6%. Additionally, levofloxacin was stable in all evaluations. The usefulness of this method was demonstrated in a pharmacokinetic study of levofloxacin in healthy adult volunteers. The present method offers two main advantages: (a) the use of microsamples reduces the total volume of blood to be collected from patients; and (b) it provides a good cost–effectiveness ratio. It is concluded that the method is rapid, simple, sensitive, economical and suitable for the determination of levofloxacin in human plasma using a small volume of sample. Copyright © 2014 John Wiley & Sons, Ltd.     

Quantification of mequitazine in human plasma by gas chromatography– quadrupole mass spectrometry and its application to a human pharmacokinetic study

A specific and sensitive gas chromatography–mass spectrometry (GC‐MS) with quadrupole mass analyzer type was developed and validated for the quantitative analysis of mequitazine in human plasma. After liquid–liquid extraction of plasma samples containing mequitazine and promethazine (internal standard, IS) using hexane with pH adjustment, the extract was evaporated and an aliquot of reconstituted residue was injected into the GC‐MS system. The assay showed linearity over a concentration range from 1 to 50 ng/mL. Intra‐ and inter‐day precision for mequitazine was <9.09 and 9.29%, respectively, and intra‐ and inter‐day accuracy ranged from ?7.97 to 9.05% and from ?1.51 to 7.89%, respectively. The lower limit of quantification was 1 ng/mL in the present assay. The developed analytical method was successfully applied to a pharmacokinetic study after a single oral administration of mequitazine in human subjects. Copyright © 2015 John Wiley & Sons, Ltd.     

Determination of chromatographic dissociation constants of some carbapenem group antibiotics and quantification of these compounds in human urine

The dissociation constant values (_s^spK_a) of some carbapenem group drugs (ertapenem, meropenem, doripenem) in different percentages of methanol–water binary mixtures (18, 20 and 22%, v/v) were determined from the mobile phase pH dependence of their retention factor. Evaluation of these data was performed using the NLREG program. From calculated pK_a values, the aqueous pK_a values of these subtances were calculated by different approaches. Moreover, the correlation established between retention factor and the pH of the water–methanol mobile phase was used to determine the optimum separation conditions. In order to validate the optimized conditions, these drugs were studied in human urine. The chromatographic separation was realized using a Gemini NX C₁₈ column (250 × 4.6 mm i.d., 5 µm particles) and UV detector set at 220 and 295 nm. Copyright © 2013 John Wiley & Sons, Ltd.     

Hapten Syntheses,Antibody Generation,and Ultrasensitive Enzyme-Linked Immunosorbent Assay for the Determination of Tonalid in Human Blood

Two novel and high-throughput enzyme-linked immunosorbent assays (ELISA) were developed for determining tonalide in human blood samples. For establishing the proposed methods, the tonalide hapten and immunogen primarily were prepared. After the immunization, the polyclonal antibody and biotinylated polyclonal antibody were obtained. The biotin-streptavidin system and polyamidoamine-gold nanoparticle conjugation were applied respectively to establish thebiotin-streptavidin-ELISA and Au-polyamidoamine-ELISA. For reducing the background interference, some factors and procedures were also discussed and optimized. Under the optimal conditions, the IC₁₀ of biotin-streptavidin-ELISA was 0.046?µg/L and the IC₁₀ of Au-polyamidoamine-ELISA was 0.016?µg/L. The Au-polyamidoamine-ELISA was used to determine tonalide in human blood and the recovery values and coefficients of variation were acceptable. In this study, tonalide was detected in 92.2% of the samples; the median and the maximum values were 0.62 and 1.76?µg/L, respectively. In general, due to the specificity of the antibody and novel nanoprobe design, this Au-polyamidoamine-ELISA simplified the sample preparation and provided a useful and potential way for trace determination of tonalide. The results also suggested that tonalide concentrations were not significantly relative to gender, but the high concentrations of tonalide in human blood should encourage further toxicological studies.