A new, cyclic carbonate eudesmane-type sesquiterpene, eudesmacarbonate (1), was isolated from marine filamentous cyanobacterial mats associated with apparent ingestion-related intoxications of captive bottlenose dolphins in the Florida Keys. Sequencing of 16S rDNA revealed that mats were composed of closely related Oscillatoriacean species including a previously undocumented species of Neolyngbya. The structure of 1 was elucidated by (+)-HRESIMS, 1D and 2D NMR, single-crystal X-ray diffraction, and vibrational circular dichroism data. Toxicity of 1 was assessed in the zebrafish embryo/larval model, and 1 was found to exhibit effects qualitatively similar to those observed for the known neurotoxin brevetoxin-2 and consistent with neurobehavioral impairment.Slow kinetics of polysulfide conversion reactions lead to severe issues for lithium-sulfur (Li-S) batteries, for example, low rate capability, polysulfide migration, and low Coulombic efficiencies. These challenges hinder the practical applications of Li-S batteries. In this study, we proposed a rational strategy of tuning the d-band of catalysts to accelerate the conversion of polysulfides. Nitrogen vacancies were engineered in hexagonal Ni3N (space group P6322) to tune its d-band center, leading to the strong interaction between polysulfides and Ni3N. Because of the greater electron population in the lowest occupied molecular orbital of Li2S4, the terminal S-S bonds were weakened for breaking. Temperature-dependent experiments confirm that Ni3N0.85 demonstrates a much low activation energy, thereby accelerating the conversion of polysulfides. A Li-S cell using Ni3N0.85 can deliver a high initial discharge capacity of 1445.9 mAh g-1 (at 0.02 C) and low decay per cycle (0.039%). The Ni3N0.85 cell can also demonstrate an initial capacity of 1200.4 mAh g-1 for up to 100 cycles at a high loading of 5.2 mg cm-2. The high efficiency of rationally designed Ni3N0.85 demonstrates the effectiveness of the d-band tuning strategy to develop low-activation-energy catalysts and to promote the atomic understanding of polysulfide conversion in Li-S batteries.CpG oligodeoxynucleotides are potent toll-like receptor (TLR) 9 agonists and have shown promise as anticancer agents in preclinical studies and clinical trials. Binding of CpG to TLR9 initiates a cascade of innate and adaptive immune responses, beginning with activation of dendritic cells and resulting in a range of secondary effects that include the secretion of pro-inflammatory cytokines, activation of natural killer cells, and expansion of T cell populations. Recent literature suggests that local delivery of CpG in tumors results in superior antitumor effects as compared to systemic delivery. In this study, we utilized PRINT (particle replication in nonwetting templates) nanoparticles as a vehicle to deliver CpG into murine lungs through orotracheal instillations. In two murine orthotopic metastasis models of non-small-cell lung cancer-344SQ (lung adenocarcinoma) and KAL-LN2E1 (lung squamous carcinoma), local delivery of PRINT-CpG into the lungs effectively promoted substantial tumor regression and also limited systemic toxicities associated with soluble CpG. Furthermore, cured mice were completely resistant to tumor rechallenge. Ki16425 Additionally, nanodelivery showed extended retention of CpG within the lungs as well as prolonged elevation of antitumor cytokines in the lungs, but no elevated levels of proinflammatory cytokines in the serum. These results demonstrate that PRINT-CpG is a potent nanoplatform for local treatment of lung cancer that has collateral therapeutic effects on systemic disease and an encouraging toxicity profile and may have the potential to treat lung metastasis of other cancer types.Thermodynamic and kinetic aspects of crystalline (c-KTP) and amorphous (a-KTP) ketoprofen dissolution in water have been investigated by molecular dynamics simulation focusing on free energy properties. Absolute free energies of all relevant species and phases have been determined by thermodynamic integration on a novel path, first connecting the harmonic to the anharmonic system Hamiltonian at low T and then extending the result to the temperature of interest. The free energy required to transfer one ketoprofen molecule from the crystal to the solution is in fair agreement with the experimental value. The absolute free energy of the amorphous form is 19.58 kJ/mol higher than for the crystal, greatly enhancing the ketoprofen concentration in water, although as a metastable species in supersaturated solution. The kinetics of the dissolution process has been analyzed by computing the free energy profile along a reaction coordinate bringing one ketoprofen molecule from the crystal or amorphous phase to the solvated state. This computation confirms that, compared to the crystal form, the dissolution rate is nearly 7 orders of magnitude faster for the amorphous form, providing one further advantage to the latter in terms of bioavailability. The problem of drug solubility, of great practical importance, is used here as a test bed for a refined method to compute absolute free energies, which could be of great interest in biophysics and drug discovery in particular.Green-to-red photoconvertible fluorescent proteins (PCFPs) are key players in advanced microscopy schemes such as photoactivated localization microscopy (PALM). Whereas photoconversion and red-state blinking in PCFPs have been studied intensively, their green-state photophysical behavior has received less attention. Yet dark states in green PCFPs can become strongly populated in PALM schemes and exert an indirect but considerable influence on the quality of data recorded in the red channel. Furthermore, green-state photoswitching in PCFPs can be used directly for PALM and has been engineered to design highly efficient reversibly switchable fluorescent proteins (RSFPs) amenable to various nanoscopy schemes. Here, we demonstrate that green mEos4b efficiently switches to a long-lived dark state through cis-trans isomerization of its chromophore, as do most RSFPs. However, by combining kinetic crystallography, molecular dynamics simulations, and Raman spectroscopy, we find that the dark state in green mEos4b is much more dynamic than that seen in switched-off green IrisFP, a biphotochromic PCFP engineered from the common EosFP parent.