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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Effects of blue light on pigment and citrinin production in Monascus ruber M7 via MrcreD, encoding an arrestin-like protein

Xiaodi Wang,Jingyi Wei,Fufang Tang,Fusheng Chen

Blue light, as an important environmental factor, greatly affects the production of Monascus pigments (MPs) and citrinin in Monascus spp.. In this study, the deletion, complementation, and overexpression mutants of MrcreD from Monascus ruber M7, which encodes an arrestin-like protein, were constructed and cultivated on PDA (Potato dextrose agar) medium to study the effects of blue light on MPs and citrinin production. The results revealed that blue light inhibited the formation of cleistothecia, conidia, and the production of MPs and citrinin in M. ruber M7. However, under blue light, in contrast to M. ruber M7, MrcreD -overexpressing strain displayed increased production of extracellular yellow pigments and intracellular orange pigments, whereas MrcreD -deleted strain showed enhanced production of intracellular yellow and orange pigments. Then, the extracellular citrinin production decreased in both mutants. The RT-qPCR results demonstrated that compared to M. ruber M7, overexpressing MrcreD increased the expression of genes involved in MPs biosynthesis, and decreased the genes involved in citrinin biosynthesis, while deleting MrcreD increased the expression of citrinin-relative genes. This is the first time that the functions of MrcreD gene in filamentous fungi have been researched under blue light, and it provides a strategy for exploring complex light-regulatory systems in filamentous fungi.

CAS / MDL: 9032-08-0
研究领域: 微生物学 · 分子生物学
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Arabian Journal of Chemistry · 2023 · IF 6

Simultaneous determination of bicyclol and its two active metabolites concentration in rat plasma and application for pharmacokinetics study of bicyclol and optimized bicyclol-nanoparticles

Xucong Huang,Zhenghua Wu,Yanchao Liu,Mengqi Jia,Wenjuan Zhao,Shuowen Wang,Xinhui Jiang,Yuefen Lou,Guorong Fan

A simple, sensitive, and rapid LC-MS/MS method for the simultaneous determination of BIC, the M7 and M8 active metabolites in SD rat plasma was developed. After salting-out assisted liquid–liquid extraction (SALLE) with 5 M ammonium acetate solution, the sample was analyzed on a Sciences column (C18 3.0 × 100 mm, 3 μm) using a gradient elution at 40 ℃ within 7 min. The assay displayed excellent linearity in the range of 4–2000 ng/mL for M7 and BIC, and 1–500 ng/mL for M8. The results of this method exhibited that the precision, accuracy, matrix effect, recovery, and stability of BIC, M7 and M8 met all requirements for the quantitation in plasma samples. The pharmacokinetic result showed that the AUC (0→t) was calculated as 383.1 ± 164.4 (ng/mL·h) for BIC, and 5627 ± 1261 (ng/mL·h) for M7 after oral administration with BIC. Compared with BIC group, the pharmacokinetic parameters in BIC-NPs group were improved. Augmentation in AUC (0→t) (3.02-fold) and t 1/2 (1.43-fold) for BIC. Meanwhile, double peak phenomenon was observed on the mean plasma concentration–time curves of M7 in BIC and BIC-NPs group. In conclusion, both BIC and BIC-NPs were metabolized to abundant M7 in SD rat, which would provide a basis for researching the treatment mechanism of liver injury.

研究领域: 药物代谢 · 药理学 · 分析化学
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SEPARATION AND PURIFICATION TECHNOLOGY · 2025 · IF 9

High-throughput continuous microfluidic magnifiable manufactured microstructured MOFs-mediated micropollutants mitigation (M7)

Gao Xiao,Jun Zhang,Mingzhu Zheng,Liyin Chen,Samson Afewerki,Manna Dai,Junling Guo

Organic micropollutants in wastewater containing arsanilic acid (p-ASA) can undergo a transformation into a highly toxic inorganic arsenic, impacting both the environment and human health. Adsorption materials such as Metal-organic frameworks (MOFs) have attracted great interest, yet their production methods are often complex, costly, and time-consuming, hindering large-scale production. We introduces an innovative, high-throughput microfluidic magnifiable manufacturing approach to expedite MOFs creation, enabling rapid, continuous, and parallel expandable scalable production of MOFs with a uniform microstructure in mere minutes, significantly outpacing the traditional, intermittently operated hydrothermal synthesis. The microfluidic-generated microstructured MF-UIO-66 has better organic arsenic adsorption capacity (333.3 mg/g), and maintained an 89.2 % effectiveness even after four cycles of reuse without generating harmful by-products. When compared to UIO-66 produced via conventional hydrothermal methods, the microfluidically synthesized MF-UIO-66 showcases not only a faster and more effective removal of varying concentrations of organic arsenic but also enhanced chemical stability and longevity. The novel microfluidic fabrication strategy holds great potential for the industrial-scale production of MF-UIO-66 at reduced costs and increased yields.

CAS / MDL: 2045-00-3 65-49-6
研究领域: 环境科学 · 材料科学
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TOXICOLOGY MECHANISMS AND METHODS · 2026 · IF 2.9

Reclassification of the main impurity (-)-scopolamine hydrobromide trihydrate in scopolamine butylbromide: an integrated ICH M7 guideline assessment combining in silico, in vitro, and in vivo studies

Rui Li,Su Zhou,Hongyan Zhu,Jing Fang,Minyang Gu,Zhiwen Ji,Liming Tang,Qingfen Zhu,Zhen Feng

Following the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) multidisciplinary guideline M7 (R2), in silico prediction, in vitro and in vivo genotoxicity evaluations were used to evaluate the potential genotoxic risk of (-)-scopolamine hydrobromide trihydrate (SHT), the main impurity of scopolamine butylbromide in the Chinese Pharmacopoeia (ChP). The 2018 in silico models for genotoxicity (Derek Nexus and Sarah Nexus) predicted SHT to be a Class 4 impurity. Subsequent in vitro and in vivo genotoxicity tests (bacterial reverse mutation test, in vitro mammalian chromosomal aberration test, in vitro mammalian cell gene mutation test and mammalian erythrocyte micronucleus test) showed no positive findings, indicating that SHT has no evidence of genotoxic potential under the tested conditions. Therefore, SHT could be tentatively categorized as a Class 5 impurity according to the ICH multidisciplinary guideline M7 (R2), with a threshold according to ICH quality guideline Q3B (R2). In silico prediction in 2026 confirmed this classification, demonstrating the high reliability of the Nexus software database for classification according to ICH multidisciplinary guideline M7 (R2). In the ChP, the SHT threshold in scopolamine butylbromide falls between the identification thresholds and the qualification thresholds of ICH quality guideline Q3B (R2), which is accurate and reasonable.

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