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Lipid droplets (LDs) are organelles with good natural biocompatibility that are abundant in eukaryotic cells and are considered good candidates for use in biological delivery inside cells. Importantly, numerous studies have reported that LDs also participate in immune processes. Here, we investigated whether LDs can also be used as vaccine adjuvants. We designed and prepared a variety of artificial nano-LDs with a nanometer size (200–300 nm) to test this possibility. Artificial nano-LDs have the same monolayer lecithin membrane as natural LDs; in contrast to natural LDs, artificial nano-LDs do not have proteins on their surfaces, which is beneficial to ensure better biocompatibility. Compared with other oil-in-water emulsion adjuvants (MF59 [AddaVax] and AS03 [AddaS03] used in licensed vaccines), vitamin E was used instead of squalene as the oil phase. The artificial nano-LDs (V3, V11, and V12) prepared in this study have structures similar to those of MF59 (AddaVax) and AS03-(AddaS03) under scanning electron microscopy and transmission electron microscopy and have better stability than MF59 (AddaVax) and AS03 (AddaS03); they can even withstand high-temperature sterilization at 120 °C for 30 min. In vivo test results showed that the artificial nano-LDs had good biocompatibility. Recombinant hepatitis B surface antigen and recombinant varicella-zoster virus glycoprotein E were used as model antigens to evaluate the adjuvant effect. We found that our artificial nano-LDs induced excellent humoral and cellular immunity (comparable to that of MF59 [AddaVax]). In addition, apart from the initial increase in the particle size upon high-temperature sterilization, the adjuvant effect of artificial nano-LDs did not decrease. [ABSTRACT FROM AUTHOR]

Regiodivergent transition-metal-catalyzed oxidative C5- and ortho -alkynylation of 2-arylthiazoles have been demonstrated. Namely, Pd(II)-catalysis selectively generated C5-alkynylated products from the reaction of 2-arylthiazoles and terminal alkynes. In contrast, Ru(II)-catalysis exclusively provided ortho -alkynylated products from the same substrates. This protocol features a wide substrate scope, good functional group tolerance, high atom-economy, and exclusive regioselectivity. The alkynylated products can be readily converted into highly valuable synthons, which hold potential for applications in the fields of medicinal chemistry and materials science.

Foam flooding is an important tool for reservoir development. This study aims to further investigate the interaction between stimulus-responsive wormlike micelle (WLM)-CO 2 foams and crude oil. We performed micromorphology experiments as our major studies and used molecular dynamics simulations as an auxiliary tool for interfacial analysis. We utilized foam generation, liquid separation, and defoaming as the entry points of experimental research and energy as the quantitative assessment index to investigate the dynamic process of the action of different oil contents and oil phase types in a DOAPA@NaSal-H + foam system. We also examined the role of NaSal in the generation and development of the foam system. Results indicated that the law of crude oil's effect on foam could be summarized as "low contents are beneficial and high contents are harmful." In addition, although the DOAPA@NaSal-H + foam system has high compatibility for saturated and aromatic hydrocarbons, it is highly suitable for application in reservoir environments with relatively high asphaltene and resin contents. Through combined experimental and simulation approaches, we clarified the law governing the stability of the DOAPA@NaSal-H + foam system in different oil-containing environments, identified the key role of NaSal, and provided a reference for the targeted application of the DOAPA@NaSal-H + foam system in different oil reservoirs.

The clinical utility of gemcitabine, an antimetabolite antineoplastic agent applied in various chemotherapy treatments, is limited due to the required intravenous injection. Although chemical structure modifications of gemcitabine result in enhanced oral bioavailability, these modifications compromise complex synthetic routes and cause unexpected side effects. In this study, gemcitabine-loaded glycocholic acid-modified micelles (Gem-PPG) were prepared for enhanced oral chemotherapy. The in vitro transport pathway experiments revealed that intact Gem-PPG were transported across the intestinal epithelial monolayer via an apical sodium-dependent bile acid transporter (ASBT)-mediated pathway. In mice, the pharmacokinetic analyses demonstrated that the oral bioavailability of Gem-PPG approached 81%, compared to less than 20% for unmodified micelles. In addition, the antitumor activity of oral Gem-PPG (30 mg/kg, BIW) was superior to that of free drug injection (60 mg/kg, BIW) in the xenograft model. Moreover, the assessments of hematology, blood chemistry, and histology all indicated the hypotoxicity profile of the drug-loaded micelles.

An efficient Pd II - and Rh III -controlled site-selective C-H bond alkynylation of imidazopyridines using (bromoethynyl)triisopropylsilane is disclosed. The divergent methodology allows straightforward access to a wide range of products alkynylated at the C3 and ortho positions. This strategy is suggestive of a practical platform that can be suitable for late-stage diversification and may assist in the design of more selective and complementary catalytic systems.

We report an Rh(I)-catalyzed C-H bond alkylation of PhenCarPhos [ N -(2-(diphenylphosphaneyl)phenyl)carbazole] and some congener phosphine ligands with alkenes. The C-H bond functionalization occurred exclusively at the C1 position of the carbazolyl unit because the trivalent phosphine acts as a directing group. This protocol provides straightforward access to a large library of C1-alkyl substituted PhenCarPhos, which outperformed common commercial or unfunctionalized phosphines and their precursors in the Pd-catalyzed carbon dioxide-fixation reactions with propargylic amines.

An efficient copper-iodine cocatalyzed intermolecular C-H aminocyanation of indoles with a broad substrate scope has been developed for the first time. This method enables highly step-economic access to 2-amino-3-cyanoindoles in moderate to good yields and provides a complementary strategy for the regioselective difunctionalization of carbon═carbon double bonds of interest in organic synthesis and related areas. Mechanistic studies suggest that these transformations are initiated by iodine-mediated C2-H amination with azoles, followed by copper-catalyzed C3-H cyanation with ethyl cyanoformate.

We report characterization of the biosynthetic pathway of the potent immunosuppressant (-)-FR901483 ( 1 ) through heterologous expression and enzymatic assays. The biosynthetic logic to form the azatricyclic alkaloid is consistent with those proposed in biomimetic syntheses and involves aza-spiro annulation of dityrosyl-piperazine to form a ketoaldehyde intermediate, followed by regioselective aldol condensation, stereoselective ketoreduction, and phosphorylation. A possible target of 1 is proposed based on the biosynthetic studies.

Biosynthetic pathways containing multiple core enzymes have potential to produce structurally complex natural products. Here we mined a fungal gene cluster that contains two predicted terpene cyclases (TCs) and a nonribosomal peptide synthetase (NRPS). We showed the flv pathway produces flavunoidine 1 , an alkaloidal terpenoid. The core of 1 is a tetracyclic, cage-like, and oxygenated sesquiterpene that is connected to dimethylcadaverine via a C-N bond and is acylated with 5,5-dimethyl-l-pipecolate. The roles of all flv enzymes are established on the basis of metabolite analysis from heterologous expression.

A four-enzyme catalyzed hydroxy regioisomerization of anthracycline was integrated into the biosynthetic pathway of aclacinomycin A (ALM-A), to generate a series of iso-ALMs via directed combinatorial biosynthesis combined with precursor-directed mutasynthesis. Most of the newly acquired iso-ALMs exhibit obviously (1-5-fold) improved antitumor activity. Therefore, we not only developed iso-ALMs with potential as clinical drugs but also demonstrated the utility of this tailoring tool for modification of anthracycline antibiotics in drug discovery and development.