粉末包衣技术在药物制剂领域的应用研究进展

粉末包衣技术是薄膜包衣技术发展至今的一个重要分支,其在药物制剂领域的应用优势突出,近年来受到药剂学研究者的广泛关注。分类综述目前应用于药物制剂的几种主要粉末包衣技术,包括属于物理化学法中的凝聚法、溶剂蒸发法和熔融分散法以及物理机械法中的喷雾干燥法、喷雾冷凝法、干法包衣技术和气流悬浮包衣技术,并探讨粉末包衣技术的主要功用,如用于制备缓控释制剂、药物粉末表面改性、改善口服制剂感官效果和提高药物及制剂稳定性等。     

合成生物制造2022

本文对2022年《生物工程学报》发表的与合成生物制造相关的综述和研究论文进行了评述,重点讨论了DNA测序、DNA合成、DNA编辑、基因表达调控和数学细胞模型等底层技术,酶的设计、改造和应用技术,化学品生物催化、氨基酸及其衍生物、有机酸、天然化合物、抗生素与活性肽、功能多糖、功能蛋白质等重要产品的生物制造技术,一碳化合物和生物质原料利用技术以及合成微生物组技术,以帮助读者从一个侧面了解合成生物制造相关技术和产业的发展情况。     

DNA水凝胶应用于环境样品快速检测的研究进展

DNA作为生物大分子既可以引导生物发育和生命机能活动,也可以被用作构筑纳米生物材料.DNA水凝胶可以制备成兼具DNA生物功能和水凝胶特质,应用于环境样品的分析检测.依据制备DNA水凝胶长链的方法,对比分析了聚合酶链反应、杂交链式反应、滚环扩增技术的制备,物理水凝胶和化学水凝胶的合成过程和改性方法技术特点;并结合环境样品...     

Action mechanism of tachyplesin I and effects of PEGylation

PEGylation of protein and peptide drugs is frequently used to improve in vivo efficacy. We investigated the action mechanism of tachyplesin I, a membrane-acting cyclic antimicrobial peptide from Tachypleus tridentatus and the effects of PEGylation on the mechanism. The PEGylated peptide induced the leakage of calcein from egg yolk l-α-phosphatidylglycerol/egg yolk l-α-phosphatidylcholine large unilamellar vesicles similarly to the parent peptide. Both peptides induced lipid flip-flop coupled to leakage and was translocated into the inner leaflet of the bilayer, indicating that tachyplesin I forms a toroidal pore and that PEGylation did not alter the basic mechanism of membrane permeabilization of the parent peptide. Despite their similar activities against model membranes, the peptides showed very different biological activities. The cytotoxicity of tachyplesin I was greatly reduced by PEGylation, although the antimicrobial activity was significantly weakened. We investigated the enhancement of the permeability of inner membranes induced by the peptides. Our results suggested that outer membranes and peptidoglycan layers play an inhibitory role in the permeation of the PEG moiety. Furthermore, a reduction in DNA binding by PEGylation may also contribute to the weak activity of the PEGylated peptide.     

Substrate-binding loop interactions with pseudouridine trigger conformational changes that promote catalytic efficiency of pseudouridine kinase PUKI

Pseudouridine, one major RNA modification, is catabolized into uracil and ribose-5′-phosphate by two sequential enzymatic reactions. In the first step, pseudouridine kinase (PUKI) phosphorylates pseudouridine to pseudouridine 5′-monophosphate. High-fidelity catalysis of pseudouridine by PUKI prevents possible disturbance of in vivo pyrimidine homeostasis. However, the molecular basis of how PUKI selectively phosphorylates pseudouridine over uridine with >100-fold greater efficiency despite minor differences in their K_m values has not been elucidated. To investigate this selectivity, in this study we determined the structures of PUKI from Escherichia coli strain B (EcPUKI) in various ligation states. The structure of EcPUKI was determined to be similar to PUKI from Arabidopsis thaliana, including an α/β core domain and β-stranded small domain, with dimerization occurring via the β-stranded small domain. In a binary complex, we show that Ser30 in the substrate-binding loop of the small domain mediates interactions with the hallmark N1 atom of pseudouridine nucleobase, causing conformational changes in its quaternary structure. Kinetic and fluorescence spectroscopic analyses also showed that the Ser30-mediated interaction is a prerequisite for conformational changes and subsequent catalysis by EcPUKI. Furthermore, S30A mutation or EcPUKI complexed with other nucleosides homologous to pseudouridine but lacking the pseudouridine-specific N1 atom did not induce such conformational changes, demonstrating the catalytic significance of the proposed Ser30-mediated interaction. These analyses provide structural and functional evidence for a pseudouridine-dependent conformational change of EcPUKI and its functional linkage to catalysis.     

Genome-wide analysis of N1-methyl-adenosine modification in human tRNAs

The N¹-methyl-Adenosine (m¹A58) modification at the conserved nucleotide 58 in the TΨC loop is present in most eukaryotic tRNAs. In yeast, m¹A58 modification is essential for viability because it is required for the stability of the initiator-tRNA^Met. However, m¹A58 modification is not required for the stability of several other tRNAs in yeast. This differential m¹A58 response for different tRNA species raises the question of whether some tRNAs are hypomodified at A58 in normal cells, and how hypomodification at A58 may affect the stability and function of tRNA. Here, we apply a genomic approach to determine the presence of m¹A58 hypomodified tRNAs in human cell lines and show how A58 hypomodification affects stability and involvement of tRNAs in translation. Our microarray-based method detects the presence of m¹A58 hypomodified tRNA species on the basis of their permissiveness in primer extension. Among five human cell lines examined, approximately one-quarter of all tRNA species are hypomodified in varying amounts, and the pattern of the hypomodified tRNAs is quite similar. In all cases, no hypomodified initiator-tRNA^Met is detected, consistent with the requirement of this modification in stabilizing this tRNA in human cells. siRNA knockdown of either subunit of the m¹A58-methyltransferase results in a slow-growth phenotype, and a marked increase in the amount of m¹A58 hypomodified tRNAs. Most m¹A58 hypomodified tRNAs can associate with polysomes in varying extents. Our results show a distinct pattern for m¹A58 hypomodification in human tRNAs, and are consistent with the notion that this modification fine tunes tRNA functions in different contexts.     

Bioresistance of poplar wood compressed by combined hydro-thermo-mechanical wood modification (CHTM): Soft rot and brown-rot

This work studied fungal bioresistance of combined hydro-thermo-mechanically modified (CHTM) poplar wood. The CHTM technique, introduced by Mohebby et al. (2009), is a combination of two wood modification techniques-hydrothermal wood modification and densification of wood. Blocks of poplar wood were initially treated hydrothermally at temperatures of 120, 150, and 180 °C for holding times of 0, 30, and 90 min. Afterwards, the treated blocks were compressed by a hot press (160 and 180 °C) for 20 min with a compression set of 60%. After the CHTM-treated blocks were dried, small specimens were cut for soft-rot and brown-rot decay tests according to ENV 807 and EN 113. Mass losses as well as metabolic moisture contents were determined in the decayed samples. Results revealed that the combination of wood modification techniques showed fungal suppression. It was also found that the hydrothermal treatment step could significantly reduce fungal attack in comparison with densification. Reduction of the mass losses was associated with the hydrothermal treatment temperature. Also, the level of metabolic moisture content was correlated with the mass losses for both fungi. Any reduction of the mass loss decreased the moisture content in the wood.     

Quantitative Analysis of the Sex Pheromone of Several Phycitid Moths by Electron-capture Gas Chromatography

β-Phenetyl alcohol and procaine hydrochloride are known to alter membrane structure. Their effects on the syntheses of tyramine oxidase and arylsulfatase were studied in Klebsiella aerogenes. β-Phenetyl alcohol inhibited the syntheses of membrane-bound tyramine oxidase and arylsulfatase, located in the periplasm, under non-repressing and derepressing conditions, but did not affect the syntheses of β-galactosidase and histidase, which are located internally. In contrast, procaine hydrochloride stimulated the synthesis of tyramine oxidase and derepressed the synthesis of arylsulfatase, but inhibited non-repressed synthesis of arylsulfatase. Thus, derepressed synthesis of cellular arylsulfatase was affected by the level of tyramine oxidase synthesis. Structural alterations in the cell membrane seem to impair the formation of active-arylsulfatase protein in the periplasmic space.