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Follicle developmental capacity and oocyte quality decline with advanced maternal age. Extracellular vesicles from human umbilical cord mesenchymal stem cells (HucMSC-EVs) act as a potential therapeutic product in the treatment of age-related ovarian dysfunction. In vitro culture (IVC) of preantral follicles is a useful method for understanding the mechanism of follicle development and is a promising means for improving female fertility. However, whether HucMSC-EVs have beneficial effects on aged follicle development during IVC has not yet been reported. Our research demonstrated that follicular development with single-addition withdrawal of HucMSC-EVs was better than that with continuous treatment with HucMSC-EVs. HucMSC-EVs facilitated the survival and growth of follicles, promoted the proliferation of granulosa cells (GCs), and improved the steroid hormone secretion of GCs during IVC of aged follicles. Both GCs and oocytes could uptake HucMSC-EVs. Moreover, we observed elevated cellular transcription in GCs and oocytes after treatment with HucMSC-EVs. The RNA sequencing (RNA-seq) results further validated that the differentially expressed genes are related to the promotion of GC proliferation, cell communication, and oocyte spindle organization. Additionally, the aged oocytes displayed a higher maturation rate, presented less aberrant spindle morphology, and expressed a higher level of the antioxidant protein Sirtuin 1 (SIRT1) after treatment with HucMSC-EVs. Our findings suggested that HucMSC-EVs can improve the growth and quality of aged follicles and oocytes in vitro through the regulation of gene transcription, which provides evidence for HucMSC-EVs as potential therapeutic reagents to restore female fertility with advanced age. [ABSTRACT FROM AUTHOR]

Diversified members of hop bitter acids (α- and β-acids) have been found in hop (Humulus lupulus). Mixtures of hop bitter acids have been traditionally applied in brewing and food industries as bitterness flavors or food additives. Recent studies have discovered novel applications of hop bitter acids and their derivatives in medicinal and pharmaceutical fields. The increasing demands of purified hop bitter acid promoted biosynthesis efforts for the heterologous biosynthesis of objective hop bitter acids by engineered microbial factories. In this study, the updated information of hop bitter acids and their representative application in brewing, food, and medicine fields are reviewed. We also speculate future trends on the development of robust microbial cell factories and biotechnologies for the biosynthesis of hop bitter acids. Key points: • Structures and applications of hop bitter acids are summarized in this study. • Biosynthesis of hop bitter acids remains challenging. • We discuss potential strategies in the microbial production of hop bitter acids. [ABSTRACT FROM AUTHOR]

In hyperlink analysis, most researchers focus on interpreting hyperlink counts, they seldom concern themselves enough about the significance of spatial distribution of hyperlinks. In this paper, we argue that not only can the inlink count to a tourist attraction's official website reflect its attractiveness, but also the spatial distribution of its inlinks can reflect the distribution of its tourist source markets. Three mountains in Anhui Province, China, are chosen for the case study. Firstly, the correlation between the spatial distributions of an attraction's tourist source markets and its official website's inlinks is investigated. Secondly, the tourism indexes such as the spatial concentration index (SCI) and the attraction radius (AR), which are calculated by inlinks, are compared to the real indexes based on tourist sources. Last, the detailed discussion and analysis are presented and an improved model, which is used to calculate the distribution of inlinks, is proposed. [ABSTRACT FROM AUTHOR]