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排序方式: 共有3721条查询结果,搜索用时 15 毫秒
1.
推导陈垃圾在滚筒筛中的运动方程并求数值解,按最大位置角将陈垃圾运动模式划分成滚落、抛落、圆周运动,给出不同筛筒转速、半径、动摩擦因数下的运动模式判别云图. 滚筒筛试验结果显示,陈垃圾运动的最大位置角随转速的升高先增大后不变,转速超过50 r/min后垃圾进行圆周运动. 陈垃圾滚筒筛的筛分效率随转速增大呈先升后降的趋势,随抛落差的增大呈持续上升的趋势,随着原料水的质量分数的增加呈下降的趋势. 基于试验结果,给出滚筒筛最优转速取值云图,在实际工程中可根据垃圾动摩擦因数及滚筒半径选择最优转速,同时减小水的质量分数以提高筛分效率.  相似文献   
2.
非口腔组织中的苦味受体(TAS2Rs)可能成为相关疾病治疗的新靶点。 该研究将表达有 TAS2Rs 的细胞作为敏感元 件,根据其生理特性与不同的传感器耦合,探究了味觉受体异位表达及其在个性化药物筛选中的应用,构建了针对不同疾病模 型的个性化药物筛选平台。 首先,基于细胞阻抗传感器以及内源性表达 TAS2R38 受体的结肠癌细胞,开发了异硫氰酸酯类物 质特异性药物筛选平台,求得苯硫脲的 EC50 为 157. 6 μM;其次,结合微电极阵列检测系统,探究了 TAS2Rs 激动剂地芬尼多 (5~ 160 μM)和水杨苷(0. 001~ 100 μM)对心肌细胞收缩的抑制作用;此外,基于 3D 呼吸道平滑肌细胞 (ASMCs) 阵列,结合凝 胶成像系统,探究了 TAS2Rs 激动剂桔皮素(20 μM)对呼吸道平滑肌细胞的舒张作用。  相似文献   
3.
Heparanase (Hpse) is an endo-β-D-glucuronidase capable of cleaving heparan sulfate side chains. Its upregulated expression is implicated in tumor growth, metastasis and angiogenesis, thus making it an attractive target in cancer therapeutics. Currently, a few small molecule inhibitors have been reported to inhibit Hpse, with promising oral administration and pharmacokinetic (PK) properties. In the present study, a ligand-based pharmacophore model was generated from a dataset of well-known active small molecule Hpse inhibitors which were observed to display favorable PK properties. The compounds from the InterBioScreen database of natural (69,034) and synthetic (195,469) molecules were first filtered for their drug-likeness and the pharmacophore model was used to screen the drug-like database. The compounds acquired from screening were subjected to molecular docking with Heparanase, where two molecules used in pharmacophore generation were used as reference. From the docking analysis, 33 compounds displayed higher docking scores than the reference and favorable interactions with the catalytic residues. Complex interactions were further evaluated by molecular dynamics simulations to assess their stability over a period of 50 ns. Furthermore, the binding free energies of the 33 compounds revealed 2 natural and 2 synthetic compounds, with better binding affinities than reference molecules, and were, therefore, deemed as hits. The hit compounds presented from this in silico investigation could act as potent Heparanase inhibitors and further serve as lead scaffolds to develop compounds targeting Heparanase upregulation in cancer.  相似文献   
4.
Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide-based compounds that target the PDZ domains of PSD-95. In contrast, developing potent and drug-like small molecules against the PSD-95 PDZ domains has so far been unsuccessful. Here, we explore the druggability of the PSD-95 PDZ1-2 domain and use fragment screening to investigate if this protein is prone to binding small molecules. We screened 2500 fragments by fluorescence polarization (FP) and validated the hits by surface plasmon resonance (SPR), including an inhibition counter-test, and found four promising fragments. Three ligand efficient fragments were shown by 1H,15N HSQC NMR to bind in the small hydrophobic P0 pockets of PDZ1-2, and one of them underwent structure-activity relationship (SAR) studies. Overall, we demonstrate that fragment screening can successfully be applied to PDZ1-2 of PSD-95 and disclose novel fragments that can serve as starting points for optimization towards small-molecule PDZ domain inhibitors.  相似文献   
5.
Understanding the ligandability of a target protein, defined as the capability of a protein to bind drug-like compounds on any site, can give important stimuli to drug-development projects. For instance, inhibition of protein–protein interactions usually depends on the identification of protein surface binders. DNA-encoded chemical libraries (DELs) allow scanning of protein surfaces with large chemical space. Encoded library selection screens uncovered several protein–protein interaction inhibitors and compounds binding to the surface of G protein-coupled receptors (GPCRs) and kinases. The protein surface-binding chemotypes from DELs are predominantly chemically modified and cyclized peptides, and functional small-molecule peptidomimetics. Peptoid libraries and structural peptidomimetics have been less studied in the DEL field, hinting at hitherto less populated chemical space and suggesting alternative library designs. Roughly a third of bioactive molecules evolved from smaller, target-focused libraries. They showcase the potential of encoded libraries to identify more potent molecules from weak, for example, fragment-like, starting points.  相似文献   
6.
PRO teolysis TA rgeting C himeras (PROTACs) promote the degradation, rather than inhibition, of a drug target as a mechanism for therapeutic treatment. Bifunctional PROTAC molecules allow simultaneous binding of both the target protein and an E3-Ubiquitin ligase, bringing the two proteins into close spatial proximity to allow ubiquitinylation and degradation of the target protein via the cell's endogenous protein degradation pathway. We utilized native mass spectrometry (MS) to study the ternary complexes promoted by the previously reported PROTAC GNE-987 between Brd4 bromodomains 1 and 2, and Von Hippel Lindeau E3-Ubiquitin Ligase. Native MS at high resolution allowed us to measure ternary complex formation as a function of PROTAC concentration to provide a measure of complex affinity and stability, whilst simultaneously measuring other intermediate protein species. Native MS provides a high-throughput, low sample consumption, direct screening method to measure ternary complexes for PROTAC development.  相似文献   
7.
In the search for the ideal model of tumours, the use of three-dimensional in vitro models is advancing rapidly. These are intended to mimic the in vivo properties of the tumours which affect cancer development, progression and drug sensitivity, and take into account cell–cell interactions, adhesion and invasiveness. Importantly, it is hoped that successful recapitulation of the structure and function of the tissue will predict patient response, permitting the development of personalized therapy in a timely manner applicable to the clinic. Furthermore, the use of co-culture systems will allow the role of the tumour microenvironment and tissue–tissue interactions to be taken into account and should lead to more accurate predictions of tumour development and responses to drugs. In this review, the relative merits and limitations of patient-derived organoids will be discussed compared to other in vitro and ex vivo cancer models. We will focus on their use as models for drug testing and personalized therapy and how these may be improved. Developments in technology will also be considered, including the use of microfluidics, 3D bioprinting, cryopreservation and circulating tumour cell-derived organoids. These have the potential to enhance the consistency, accessibility and availability of these models.  相似文献   
8.
洪帆  宋洁  杜冰  郑环达  郑来久 《精细化工》2021,38(12):2377-2384
细菌纤维素(BC)是微生物生长过程中产生的以葡萄糖为基本骨架的结构性碳水化合物,具有高纯度、高聚合度、高结晶度、高持水性、高抗张强度和良好的机械强度,在功能材料领域显示了巨大的应用潜力.综述了近年来BC合成菌种筛选的研究现状;分析了BC在透气、吸湿排汗、力学性能和染色与脱色性能调控方面的进展情况;重点总结了BC基材料在抗菌、防紫外线、防辐射、防静电、拒水拒油、导电和传感等功能化改性方面的研究进展;最后,指出BC大规模高效成模和成型技术、差异化高功能BC材料制备技术是未来的重点研发方向.  相似文献   
9.
为提高酸菜的品质,从自然发酵酸菜中分离得到1株高产L-乳酸的乳酸菌,编号为LZH-3。响应面法对其液体发酵条件进行优化,通过回归分析得出最佳发酵条件:发酵温度为33℃、接种量为3%,初始pH值为6.2,发酵时间为20 h。在此优化条件下L-乳酸产量为28.17 g/L,是优化前的1.25倍。  相似文献   
10.
建立高效液相色谱-四极杆-飞行时间质谱快速筛查胡椒粉中169 种农药残留的分析方法。样品采用0.1%乙酸溶液浸泡,乙腈溶液提取,C18和Florisil吸附剂净化,净化液采用C18色谱柱(100 mm×2.1 mm,2.6 μm)分离,以5 mmol/L甲酸铵溶液-甲醇为流动相,梯度洗脱,在电喷雾正离子模式下检测,基质匹配外标法定量,同时建立169 种农药的一级精确质量数据库和二级碎片质谱库,实现胡椒粉样品中多目标农残的快速定性定量分析。方法验证结果表明,在5~100 ng/mL质量浓度范围内,136 种化合物线性关系良好(R2>0.95),可进行定量分析,另外33 种化合物可进行定性分析;在3 个加标水平下胡椒粉样品的回收率为26%~140%,相对标准偏差为1.5%~36.0%。该方法操作简便、耗时短,适用于胡椒粉样品中高通量农药残留的快速筛查与定量分析,具有实际应用价值。  相似文献   
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