Direct Access to Highly Functionalized Heterocycles through the Condensation of Cyclic Imines and α‑Oxoesters

A facile, gram-scale preparation of 2-hydroxy-5,6,7,7a-tetrahydro-3<i>H</i>-pyrrolizin-3-ones and 2-hydroxy-6,7,8,8a-tetrahydroindolizin-3­(5<i>H</i>)-ones from a condensation cyclization of α-oxoesters with five- and six-membered cyclic imines, respectively, is reported. This transformation enables a concise, three-step synthesis of the natural products phenopyrrozin and <i>p</i>-hydroxyphenopyrrozin. Further, biologically relevant scaffolds, such as α-quaternary β-homo prolines and β-lactams, are also prepared in two- to three-steps from the versatile 2-hydroxy-5,6,7,7a-tetrahydro-3<i>H</i>-pyrrolizin-3-one core

Membrane Integrated liposome Synthesized by a Liposome Fusion-Induced Membrane Exchange

Biogenic extracellular vesicles (EVs) from mammalian cells and bacteria are assembled by lipid bilayer membrane with carried biologically active cargos such as proteins and mRNA, which received enormous attention due to their various potential applications, including immune therapy, drug delivery system, catalysis, liquid biopsy, microbial fuel cells, and so on. However, scanty EVs produced by biogenesis limited their applicability in the actual condition, and therefore new technologies to enlarge the production of EVs must be developed and remain the challenge. In this study, we created a novel method named LIME (liposome fusion-induced membrane exchange) to acquire a large quantity of biologically active vesicles, in which the excess lipid components fused into the cell’s membrane, thus promoting the process of EVs liberation. This method was first verified in gram-negative bacteria, Shewanella oneidensis MR-1 with c-type cytochrome complex (Cyts) on the outer-membrane and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine contained liposomes as the lipid donor were used. Interestingly, the significant difference in spectroscopy and heme staining between original liposomes and active membrane-integrated liposomes (MILs) revealed that the electrochemically active Cyts migrate from MR-1 outer-membrane to the liposome successfully. Moreover, MILs with Cyts enabled enhancing the current production from Escherichia coli K-12, demonstrating that the electron transfer activity of Cyts was preserved after the LIME process, and MILs showed massive potential as drug carriers, vaccine, and a tool for strains-crossed membrane proteins migration. Our approach indicates an all-new direction to produce artificial EVs with specific proteins and functions, which will significantly benefit the future development of EVs

Enhancing <i>Monascus</i> Pellet Formation for Improved Secondary Metabolite Production

Filamentous fungi are well-known for their ability to form mycelial pellets during submerged cultures, a characteristic that has been extensively studied and applied. However, Monascus, a filamentous saprophytic fungus with a rich history of medicinal and culinary applications, has not been widely documented for pellet formation. This study aimed to investigate the factors influencing pellet formation in Monascus and their impact on citrinin production, a key secondary metabolite. Through systematic exploration, we identified pH and inoculum size as critical factors governing pellet formation. Monascus exhibited optimal pellet growth within the acidic pH range from 5 to 6, resulting in smaller, more homogeneous pellets with lower citrinin content. Additionally, we found that inoculum size played a vital role, with lower spore concentrations favoring the formation of small, uniformly distributed pellets. The choice of carbon and nitrogen sources also influenced pellet stability, with glucose, peptone, and fishmeal supporting stable pellet formation. Notably, citrinin content was closely linked to pellet diameter, with larger pellets exhibiting higher citrinin levels. Our findings shed light on optimizing Monascus pellet formation for enhanced citrinin production and provide valuable insights into the cultivation of this fungus for various industrial applications. Further research is warranted to elucidate the molecular mechanisms underlying these observations

Overview of the 2017 Spoken CALL Shared Task

We present an overview of the shared task for spoken CALL. Groups competed on a prompt-response task using English-language data collected, through an online CALL game, from Swiss German teens in their second and third years of learning English. Each item consists of a written German prompt and an audio file containing a spoken response. The task is to accept linguistically correct responses and reject linguistically incorrect ones, with “linguistically correct” being defined by a gold standard derived from human annotations; scoring was performed using a metric defined as the ratio of the relative rejection rates on incorrect and correct responses. The task received twenty entries from nine different groups. We present the task itself, the results, a tentative analysis of what makes items challenging, a comparison between different metrics, and suggestions for a continuation

Electrosprayed Ultra-Thin Coating of Ethyl Cellulose on Drug Nanoparticles for Improved Sustained Release

In nanopharmaceutics, polymeric coating is a popular strategy for modifying the drug release kinetics and, thus, new methods for implementing the nanocoating processes are highly desired. In the present study, a modified coaxial electrospraying process was developed to formulate an ultra-thin layer of ethyl cellulose (EC) on a medicated composite core consisting of tamoxifen citrate (TAM) and EC. A traditional single-fluid blending electrospraying and its monolithic EC-TAM nanoparticles (NPs) were exploited to compare. The modified coaxial processes were demonstrated to be more continuous and robust. The created NPs with EC coating had a higher quality than the monolithic ones in terms of the shape, surface smoothness, and the uniform size distribution, as verified by the SEM and TEM results. XRD patterns suggested that TAM presented in all the NPs in an amorphous state thanks to the fine compatibility between EC and TAM, as indicated by the attenuated total reflection (ATR)-FTIR spectra. In vitro dissolution tests demonstrated that the NPs with EC coating required a time period of 7.58 h, 12.79 h, and 28.74 h for an accumulative release of 30%, 50%, and 90% of the loaded drug, respectively. The protocols reported here open a new way for developing novel medicated nanoparticles with functional coating