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61.
Stefano Agnello Michael Brand Mathieu F. Chellat Silvia Gazzola Rainer Riedl 《Angewandte Chemie (International ed. in English)》2019,58(11):3300-3345
The natural phenomenon of drug resistance is a widespread issue that hampers the performance of drugs in many major clinical indications. Antibacterial and antifungal drugs are affected, as well as compounds for the treatment of cancer, viral infections, or parasitic diseases. Despite the very diverse set of biological targets and organisms involved in the development of drug resistance, the underlying molecular mechanisms have been identified to understand the emergence of resistance and to overcome this detrimental process. Detailed structural information on the root causes for drug resistance is nowadays frequently available, so next‐generation drugs can be designed that are anticipated to suffer less from resistance. This knowledge‐based approach is essential for fighting the inevitable occurrence of drug resistance. 相似文献
62.
测定金属电阻温度系数的方法研究 总被引:3,自引:0,他引:3
从金属电阻率与温度的线性关系出发,设计了测定金属电阻温度系数的实验方案。利用基本的电磁学仪器和热学仪器组合进行实验,以漆包铜线作为待测金属丝测定出铜的电阻温度系数,分析了导致系统误差产生的主要原因,并就待测金属丝的选取原则、温度控制的方法进行了讨论。 相似文献
63.
采用聚醚改性三硅氧烷表面活性剂、 丙烯酸酯改性硅油和水3种组分制备了稳定的油包水(W/O)乳液, 经酸碱催化水解、 紫外引发聚合和干燥除水过程得到了双网络多孔有机硅弹性体. 扫描电子显微镜(SEM)分析结果表明, 所制备的有机硅弹性体具有丰富的孔径结构分布. 压缩强度测试结果表明, 弹性体具备良好的耐压缩性能, 45%压缩应变下循环50次, 仍具备良好的回弹性能. 有机硅弹性体具有优异的耐高温性能, 分解温度为370 ℃, 高于绝大多数多孔有机硅弹性体材料的分解温度. 丙烯酸酯改性硅油的制备工艺成熟、 廉价易得, 显著降低了多孔有机硅弹性体的生产成本, 为规模性开发有机硅材料提供了新的思路和应用前景. 相似文献
64.
Dr. Andreas A. Bastian Dr. Maria Bastian Dr. Manuel Jäger Mark Loznik Dr. Eliza M. Warszawik Xintong Yang Dr. Nabil Tahiri Dr. Peter Fodran Prof. Dr. Martin D. Witte Anne Thoma Dr. Jens Köhler Prof. Dr. Adriaan J. Minnaard Prof. Dr. Andreas Herrmann 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(36):e202200883
The continuous emergence of antimicrobial resistance is causing a threat to patients infected by multidrug-resistant pathogens. In particular, the clinical use of aminoglycoside antibiotics, broad-spectrum antibacterials of last resort, is limited due to rising bacterial resistance. One of the major resistance mechanisms in Gram-positive and Gram-negative bacteria is phosphorylation of these amino sugars at the 3’-position by O-phosphotransferases [APH(3’)s]. Structural alteration of these antibiotics at the 3’-position would be an obvious strategy to tackle this resistance mechanism. However, the access to such derivatives requires cumbersome multi-step synthesis, which is not appealing for pharma industry in this low-return-on-investment market. To overcome this obstacle and combat bacterial resistance mediated by APH(3’)s, we introduce a novel regioselective modification of aminoglycosides in the 3’-position via palladium-catalyzed oxidation. To underline the effectiveness of our method for structural modification of aminoglycosides, we have developed two novel antibiotic candidates overcoming APH(3’)s-mediated resistance employing only four synthetic steps. 相似文献
65.
Dr. Giambattista Testolin Dr. Jana Richter Antje Ritter Dr. Hans Prochnow Prof. Dr. Jesko Köhnke Prof. Dr. Mark Brönstrup 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(54):e202201297
The rise of antibiotic resistance causes a serious health care problem, and its counterfeit demands novel, innovative concepts. The combination of photopharmacology, enabling a light-controlled reversible modulation of drug activity, with antibiotic drug design has led to first photoswitchable antibiotic compounds derived from established scaffolds. In this study, we converted cystobactamids, gyrase-inhibiting natural products with an oligoaryl scaffold and highly potent antibacterial activities, into photoswitchable agents by inserting azobenzene in the N-terminal part and/or an acylhydrazone moiety near the C-terminus, yielding twenty analogs that contain mono- as well as double-switches. Antibiotic and gyrase inhibition properties could be modulated 3.4-fold and 5-fold by light, respectively. Notably, the sensitivity of photoswitchable cystobactamids towards two known resistance factors, the peptidase AlbD and the scavenger protein AlbA, was light-dependent. While irradiation of an analog with an N-terminal azobenzene with 365 nm light led to less degradation by AlbD, the AlbA-mediated inactivation was induced. This provides a proof-of-principle that resistance towards photoswitchable antibiotics can be optically controlled. 相似文献
66.
针对传统暂堵酸化用暂堵剂颗粒耐酸性差、降解性差和除堵工艺复杂等问题,本研究通过水溶液自由基聚合法制备了一种新型的自降解暂堵剂CQZDJ。考察了单体加量、交联剂加量、引发剂加量对CQZDJ凝胶强度和降解性的影响;通过FT-IR、TGA、SEM对其结构进行表征;并对其降解机理进行了探讨;最后在长8区块的环平81-8实验井进行了现场实践。结果表明:CQZDJ凝胶强度及降解时间与单体加量、交联剂加量、引发剂加量成正比关系,且降解时间可控;降解性实验表明CQZDJ在(1%~10%)HCl溶液、水、(2%~10%)NaCl溶液中均可在4 d内完全降解,具备良好的降解性能,对地层伤害小;SEM照片显示CQZDJ的降解过程是从初始三维网状结构逐渐崩解为层状结构,最终降解为无规则线性小分子链的过程;暂堵后现场流压上升6.3 MPa,日产油由3.87 t/d增产至5.22 t/d,实现了储层的有效改造,增产效果显著。 相似文献
67.
Aleš Podgornik 《Journal of separation science》2022,45(12):1984-1996
Modern convection-based supports differ substantially in pore size, porosity, and microstructure topology. Due to such variability, it is challenging to evaluate the contribution of a particular microstructure topology on flow resistance. We demonstrated that the flow resistance parameter ( ) introduced decades ago can be used as a criterion to evaluate the effect of microstructure topology on a pressure drop when the pore size is used as a characteristic support dimension. Furthermore, the value of simple cubic packing was calculated over the entire range of open porosity and compared to the values determined for pressure drop models derived for particular convection-based supports and experimental values of various convection-based supports from the literature. It was shown that different convection-based supports become clustered into distinct groups when plotted according to their and open porosity values, allowing their discrimination. 相似文献
68.
基质辅助激光解析/电离飞行时间质谱(MALDI-TOF MS)是一种新型软电离生物质谱,具有检测速度快、操作简便、结果准确等优点,目前已成为可靠的微生物快速鉴定技术。就工作流程而言,与常规生化方法相比,MALDI-TOF MS可以将微生物鉴定的时间缩短为一天甚至更短。对于具有抗生素耐药性的微生物,使用MALDI-TOF MS鉴定也有很好的准确性。在病毒鉴定中,MALDI-TOF MS也可以发挥作用,已有报道将MALDI-TOF MS和机器学习(ML)分析方法结合来检测鼻拭子中SARS-CoV-2。此外,MALDI-TOF MS还可用于细菌的无光谱库鉴定。目前,MALDI-TOF MS正通过与其他技术(例如傅里叶红外光谱FTIR)相结合进一步扩大微生物鉴定范围。 相似文献
69.
Monisha Prasad Selvaraj Jayaraman Mohamed Ahmed Eladl Mohamed El-Sherbiny Mosaab Abdella Ebrahim Abdelrahman Vishnu Priya Veeraraghavan Srinivasan Vengadassalapathy Vidhya Rekha Umapathy Shazia Fathima Jaffer Hussain Kalaiselvi Krishnamoorthy Durairaj Sekar Chella Perumal Palanisamy Surapaneni Krishna Mohan Ponnulakshmi Rajagopal 《Molecules (Basel, Switzerland)》2022,27(5)
Natural products in the form of functional foods have become increasingly popular due to their protective effects against life-threatening diseases, low risk of adverse effects, affordability, and accessibility. Plant components such as phytosterol, in particular, have drawn a lot of press recently due to a link between their consumption and a modest incidence of global problems, such as Type 2 Diabetes mellitus (T2DM), cancer, and cardiovascular disease. In the management of diet-related metabolic diseases, such as T2DM and cardiovascular disorders, these plant-based functional foods and nutritional supplements have unquestionably led the market in terms of cost-effectiveness, therapeutic efficacy, and safety. Diabetes mellitus is a metabolic disorder categoriszed by high blood sugar and insulin resistance, which influence major metabolic organs, such as the liver, adipose tissue, and skeletal muscle. These chronic hyperglycemia fallouts result in decreased glucose consumption by body cells, increased fat mobilisation from fat storage cells, and protein depletion in human tissues, keeping the tissues in a state of crisis. In addition, functional foods such as phytosterols improve the body’s healing process from these crises by promoting a proper physiological metabolism and cellular activities. They are plant-derived steroid molecules having structure and function similar to cholesterol, which is found in vegetables, grains, nuts, olive oil, wood pulp, legumes, cereals, and leaves, and are abundant in nature, along with phytosterol derivatives. The most copious phytosterols seen in the human diet are sitosterol, stigmasterol, and campesterol, which can be found in free form, as fatty acid/cinnamic acid esters or as glycosides processed by pancreatic enzymes. Accumulating evidence reveals that phytosterols and diets enriched with them can control glucose and lipid metabolism, as well as insulin resistance. Despite this, few studies on the advantages of sterol control in diabetes care have been published. As a basis, the primary objective of this review is to convey extensive updated information on the possibility of managing diabetes and associated complications with sterol-rich foods in molecular aspects. 相似文献
70.
Nina Rembiakowska Vitalij Novickij Dagmara Baczyska Magda Dubiska-Magiera Jolanta Saczko Julia Rudno-Rudziska Magdalena Maciejewska Julita Kulbacka 《Molecules (Basel, Switzerland)》2022,27(7)
(1) Background: Pulsed electric field (PEF) techniques are commonly used to support the delivery of various molecules. A PEF seems a promising method for low permeability drugs or when cells demonstrate therapy resistance and the cell membrane becomes an impermeable barrier. (2) Methods: In this study, we have used doxorubicin-resistant and sensitive models of human breast cancer (MCF-7/DX, MCF-7/WT) and colon cancer cells (LoVo, LoVoDX). The study aimed to investigate the susceptibility of the cells to doxorubicin (DOX) and electric fields in the 20–900 ns pulse duration range. The viability assay was utilized to evaluate the PEF protocols’ efficacy. Cell confluency and reduced glutathione were measured after PEF protocols. (3) Results: The obtained results showed that PEFs significantly supported doxorubicin delivery and cytotoxicity after 48 and 72 h. The 60 kV/cm ultrashort pulses × 20 ns × 400 had the most significant cytotoxic anticancer effect. The increase in DOX concentration provokes a decrease in cell viability, affected cell confluency, and reduced GSSH when combined with the ESOPE (European Standard Operating Procedures of Electrochemotherapy) protocol. Additionally, reactive oxygen species after PEF and PEF-DOX were detected. (4) Conclusions: Ultrashort electric pulses with low DOX content or ESOPE with higher DOX content seem the most promising in colon and breast cancer treatment. 相似文献