Natural Products in Preventing Tumor Drug Resistance and Related Signaling Pathways

Drug resistance is still an obstacle in cancer therapy, leading to the failure of tumor treatment. The emergence of tumor drug resistance has always been a main concern of oncologists. Therefore, overcoming tumor drug resistance and looking for new strategies for tumor treatment is a major focus in the field of tumor research. Natural products serve as effective substances against drug resistance because of their diverse chemical structures and pharmacological effects. We reviewed the signaling pathways involved in the development of tumor drug resistance, including Epidermal growth factor receptor (EGFR), Renin-angiotensin system (Ras), Phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), Wnt, Notch, Transforming growth factor-beta (TGF-β), and their specific signaling pathway inhibitors derived from natural products. This can provide new ideas for the prevention of drug resistance in cancer therapy.     

Metabolic Engineering of Shikimic Acid Biosynthesis Pathway for the Production of Shikimic Acid and Its Branched Products in Microorganisms: Advances and Prospects

The shikimate pathway is a necessary pathway for the synthesis of aromatic compounds. The intermediate products of the shikimate pathway and its branching pathway have promising properties in many fields, especially in the pharmaceutical industry. Many important compounds, such as shikimic acid, quinic acid, chlorogenic acid, gallic acid, pyrogallol, catechol and so on, can be synthesized by the shikimate pathway. Among them, shikimic acid is the key raw material for the synthesis of GS4104 (Tamiflu^®), an inhibitor of neuraminidase against avian influenza virus. Quininic acid is an important intermediate for synthesis of a variety of raw chemical materials and drugs. Gallic acid and catechol receive widespread attention as pharmaceutical intermediates. It is one of the hotspots to accumulate many kinds of target products by rationally modifying the shikimate pathway and its branches in recombinant strains by means of metabolic engineering. This review considers the effects of classical metabolic engineering methods, such as central carbon metabolism (CCM) pathway modification, key enzyme gene modification, blocking the downstream pathway on the shikimate pathway, as well as several expansion pathways and metabolic engineering strategies of the shikimate pathway, and expounds the synthetic biology in recent years in the application of the shikimate pathway and the future development direction.     

Optimized Selection of Water Resource Allocation Schemes Based on Improved Connection Entropy in Beijing’s Southern Plain

Increased urbanization has caused problems such as increasing water consumption and the continuous deterioration of the groundwater environment. It is necessary to consider the groundwater quality in the water resource optimization system and increase the rate of reclaimed water development to reduce the amount of groundwater exploitation and achieve sustainable development of water resources. This study used the Daxing District, a region of Beijing’s southern plain, as an example to evaluate water quality by analyzing water quality data of surface and groundwater from 2012 to 2016 and actual water-use schemes from 2006 to 2016. Three groundwater extraction modes were set up based on NO₃–N concentrations, water resources were optimized under three extraction modes, and water resource optimization schemes were determined based on the improved connection entropy. The results show that (1) the surface water quality was poor, and the proportion of V₄ type water in the indexes of NH₃–N and chemical oxygen demand (COD) was the largest. The surface water can only be used for agricultural irrigation. The pollution sources contributing most to NH₃–N and COD were domestic and agricultural pollution sources. (2) The groundwater quality was good. The NO₃–N index was primarily type I–III water, accounting for 95.20% of the total samples. Severe NH₃–N pollution areas were mainly in the northern region, and most regional groundwater can be used for various purposes. (3) Taking 2016 as an example, three groundwater exploitation modes were set to optimize water resource allocation, and the results showed that the rate of groundwater development and NO₃–N pollution decreased significantly after optimization. (4) Connection entropy is an evaluation method that combines connection numbers and entropy, including identify, difference, and opposition entropy. As connection entropy being a kind of complete entropy, which can reflect the difference of the system in different states, based on the improved connection entropy, the connection entropies of optimal water resource allocation and actual water-use schemes were calculated. The connection entropy of groundwater exploitation mode 3 was less than that of groundwater exploitation modes 1 and 2 and actual water-use schemes from 2006 to 2016. Therefore, exploitation mode 3’s water resource optimization scheme was recommended. In the paper, satisfactory results have been obtained. As a kind of complete entropy, connection entropy has great research value in dealing with complex hydrological problems. This study’s research methods and outcomes can provide methodological and theoretical lessons for water management in freshwater-deficient areas.     

芦丁对血清白蛋白构象的影响

用同步荧光光谱法和圆二色谱法研究了芦丁对牛血清白蛋白(BSA)和人血清白蛋白(HSA)构象和功能的影响,同时用电化学方法研究了芦丁与血清白蛋白之间的结合作用。在体内随着芦丁浓度的增加,其与血清白蛋白结合时对血清白蛋白的构象无影响,但对血清白蛋白的二级结构有影响,导致α-螺旋结构减少,β-折叠结构增加,蛋白质的二级结构被破坏。电化学研究发现：芦丁的氧化还原电流随着血清白蛋白浓度的增加而明显降低, 表明芦丁与血清白蛋白发生反应,生成比较稳定的复合物。芦丁的氧化还原最大峰电位也随着血清白蛋白浓度的增加发生变化,峰电位差略增加,表明芦丁的氧化还原性随着血清白蛋白浓度的增加而增强。进一步证明芦丁在体内能够被血清白蛋白存储和转运。     

Palladium-catalyzed hydrosilylation of ynones to access silicon-stereogenic silylenones by stereospecific aromatic interaction-assisted Si–H activation

Hydrosilylation is one of the most important reactions in synthetic chemistry and ranks as a fundamental method to access organosilicon compounds in industrial and academic processes. However, the enantioselective construction of chiral-at-silicon compounds via catalytic asymmetric hydrosilylation remained limited and difficult. Here we report a highly enantioselective hydrosilylation of ynones, a type of carbonyl-activated alkynes, using a palladium catalyst with a chiral binaphthyl phosphoramidite ligand. The stereospecific hydrosilylation of ynones affords a series of silicon-stereogenic silylenones with up to 94% yield, 20:1 regioselectivity and 98:2 enantioselectivity. The density functional theory(DFT) calculations were conducted to elucidate the reaction mechanism and origin of high degree of stereoselectivity, in which the powerful potential of aromatic interaction in this reaction is highlighted by the multiple C–H-π interaction and aromatic cavity-oriented enantioselectivitydetermining step during desymmetric functionalization of Si–H bond.     

Tm-Doped Fibre Laser Pumped Cr^2＋：ZnSe Poly-Crystal Laser

Demonstrations of cw lasing in Cr^2＋：ZnSe poly-crystal are reported. The laser consists of a 1.7-mm-thick Cr^2＋ ：ZnSe poly-crystal disc pumped by a Tin-silica double-clad fibre laser at 2050nm. Using a concave high- reflection mirror with a radius of curvature of 500mm as the rear mirror, the laser delivers up to 1030mW of radiation around 2.367μm.     

互感系数M12=M21的证明

从定义、磁能、磁矢势、磁偶极子、自由能5个方面出发分别证明了互感系数M12=M21,并对几种证明方法进行了分析对比,提出了自己的看法.     

基于模糊逻辑的红外相机模拟器定量化仿真度评价框架

针对红外相机模拟器仿真度量化评价体系的现状,提出了一种基于模糊逻辑和模糊集思想的全新的理论框架.该框架是一种客观的、多尺度的评价体系,涉及到模糊逻辑、曲线相似度评价、图像质量评估以及信息论等多个交叉领域.和现有的单一尺度的评价方法相比,这种多尺度的仿真度评价分析系统综合考虑了成像系统的主要性能特性参量和系统输出图像的质量,具有更好的任务适应性,可以方便地量化和比较具有相同或相似需求的相机模拟器的仿真度结果.     

A Docosahexaenoic Acid Derivative (N-Benzyl Docosahexaenamide) as a Potential Therapeutic Candidate for Treatment of Ovarian Injury in the Mouse Model

Commonly used clinical chemotherapy drugs, such as cyclophosphamide (CTX), may cause injury to the ovaries. Hormone therapies can reduce the ovarian injury risk; however, they do not achieve the desired effect and have obvious side effects. Therefore, it is necessary to find a potential therapeutic candidate for ovarian injury after chemotherapy. N-Benzyl docosahexaenamide (NB-DHA) is a docosahexaenoic acid derivative. It was recently identified as the specific macamide with a high degree of unsaturation in maca (Lepidium meyenii). In this study, the purified NB-DHA was administered intragastrically to the mice with CTX-induced ovarian injury at three dose levels. Blood and tissue samples were collected to assess the regulation of NB-DHA on ovarian function. The results indicated that NB-DHA was effective in improving the disorder of estrous cycle, and the CTX+NB-H group can be recovered to normal levels. NB-DHA also significantly increased the number of primordial follicles, especially in the CTX+NB-M and CTX+NB-H groups. Follicle-stimulating hormone and luteinizing hormone levels in all treatment groups and estradiol levels in the CTX+NB-H group returned to normal. mRNA expression of ovarian development-related genes was positive regulated. The proportion of granulosa cell apoptosis decreased significantly, especially in the CTX+NB-H group. The expression of anti-Müllerian hormone and follicle-stimulating hormone receptor significantly increased in ovarian tissues after NB-DHA treatment. NB-DHA may be a promising agent for treating ovarian injury.     

The Potential Antidepressant Action of Duloxetine Co-Administered with the TAAR1 Receptor Agonist SEP-363856 in Mice

Here, we explored the possible interaction between duloxetine and SEP-363856 (SEP-856) in depression-related reactions. The results showed that oral administration of duloxetine showed powerful antidepressant-like effects in both the forced swimming test (FST) and the suspension tail test (TST). SEP-856 orally administered alone also exerted an antidepressant-like effect in FST and TST, especially at doses of 0.3, 1, and 10 mg/kg. In addition, duloxetine (15 mg/kg) and SEP-856 (15 mg/kg) both showed antidepressant-like effects in the sucrose preference test (SPT). Most importantly, in the above experiments, compared with duloxetine alone, the simultaneous use of duloxetine and SEP-856 caused a more significant antidepressant-like effect. It is worth noting that doses of drug combination in FST and TST did not change the motor activities of mice in the open-field test (OFT). Thus, duloxetine and SEP-856 seem to play a synergistic role in regulating depression-related behaviors and might be beneficial for refractory depression.