Distal appendages (DAPs) are nanoscale, pinwheel-like structures protruding from the distal end of the centriole that mediate membrane docking during ciliogenesis, marking the cilia base around the ciliary gate. Here we determine a super-resolved multiplex of 16 centriole-distal-end components. Surprisingly, rather than pinwheels, intact DAPs exhibit a cone-shaped architecture with components filling the space between each pinwheel blade, a new structural element we term the distal appendage matrix (DAM). Specifically, CEP83, CEP89, SCLT1, and CEP164 form the backbone of pinwheel blades, with CEP83 confined at the root and CEP164 extending to the tip near the membrane-docking site. By contrast, FBF1 marks the distal end of the DAM near the ciliary membrane. Strikingly, unlike CEP164, which is essential for ciliogenesis, FBF1 is required for ciliary gating of transmembrane proteins, revealing DAPs as an essential component of the ciliary gate. Our findings redefine both the structure and function of DAPs.

We show that intercalation of cations (Na+, Ca2+, Ni2+, and Co2+) into the interlayer region of 1T-MoS2 is an effective strategy to lower the overpotential for the hydrogen evolution reaction (HER). In acidic media the onset potential for 1T-MoS2 with intercalated ions is lowered by ∼60 mV relative to that for pristine 1T-MoS2 (onset of ∼180 mV). Density functional theory (DFT) calculations show a lowering in the Gibbs free energy for H-adsorption (ΔG H) on these intercalated structures relative to intercalant-free 1T-MoS2. The DFT calculations suggest that Na+ intercalation results in a ΔG H close to zero. Consistent with calculation, experiments show that the intercalation of Na+ ions into the interlayer region of 1T-MoS2 results in the lowest overpotential for the HER.

Curcumin is a natural substance that exhibits the ability to inhibit and/or treat carcinogenesis in a variety of cell lines, but because of its poor solubility in water the treatment efficacy is limited. In this paper we report on the fabrication of self-assembled micelle nanoparticles loaded with a curcumin drug by use of a biocompatible copolymer of PLA-TPGS (d-a-tocopheryl polyethylene glycol 1000 succinate—vitamin E TPGS) conjugate. The polylactide (PLA)-TPGS copolymer synthesized by ring-opening polymerization was characterized by Fourier transform infrared spectroscopy (FTIR) and 1 H nuclear magnetic resonance (1 H NMR) techniques. The surface morphology of PLA-TPGS and curcumin loaded PLA-TPGS was determined by field emission scanning electron microscopy (FE-SEM). The absorption and fluorescence examinations indicated that due to micellar capsulation the intensity of both types of spectra increased by about 4 times in comparison with those of the free curcumin sample.

Efficiency is a key organizing principle in modern natural product synthesis. Practical criteria include time, cost, and effort expended to synthesize the target, which tracks with step-count and scale. The execution of a natural product synthesis, that is, the sum and identity of each reaction employed therein, falls along a continuum of chemical (abiotic) synthesis on one extreme, followed by the hybrid chemoenzymatic approach, and ultimately biological (biosynthesis) on the other, acknowledging the first synthesis belongs to Nature. Starting materials also span a continuum of structural complexity approaching the target with constituent elements on one extreme, followed by petroleum-derived and "chiral pool" building blocks, and complex natural products (i.e., semisynthesis) on the other. Herein, we detail our approach toward realizing the first synthesis of (−)-melodinine K, a complex bis-indole alkaloid. The total syntheses of monomers (−)-tabersonine and (−)-16-methoxytabersonine employing our domino Michael/Mannich annulation is described. Isolation of (−)-tabersonine from Voacanga africana and strategic biotransformation with tabersonine 16-hydroxylase for sitespecific C−H oxidation enabled a scalable route. The Polonovski−Potier reaction was employed in biomimetic fragment coupling. Subsequent manipulations delivered the target. We conclude with a discussion of efficiency in natural products synthesis and how chemical and biological technologies define the synthetic frontier.