Supplemental Material - Granulin in renal tubular epithelia is associated with interstitial inflammation and activates the TLR9-IFN-α pathway in lupus nephritis

Supplemental Material for Granulin in renal tubular epithelia is associated with interstitial inflammation and activates the TLR9-IFN-α pathway in lupus nephritis by Lanting Huang, Yijun Dai, Zhenbo Geng, Hongyan He and Fuyuan Hong</p

Zwitterionic Cocrystals of Flavonoids and Proline: Solid-State Characterization, Pharmaceutical Properties, and Pharmacokinetic Performance

We utilized the concepts of crystal engineering to acquire cocrystals of d/l-proline with a variety of flavonoids and further evaluated the impact on solubility and pharmacokinetic of flavonoids. We have synthesized and characterized six d/l-proline cocrystals with flavonoids and their single crystal structures were revealed. The powder dissolution profiles were determined and the pharmacokinetic properties for Kae-l-Pro were analyzed and compared with the corresponding physical mixture. d/l-Proline was found to be a suitable coformer for a variety of structural similar flavonoids. This study may offer an alternative approach for the development of these widely used flavonoids

Modulating the Dissolution and Mechanical Properties of Resveratrol by Cocrystallization

Resveratrol (RSV), a dietary polyphenol found in red wine, has renewed interest in recent years due to a broad range of in vitro evidence that indicate cardioprotective effects. Herein, we have synthesized four RSV cocrystals with the objective to improve the physicochemical and mechanical properties. Single crystal structures were illustrated and comprehensive characterization of the cocrystals were performed. In addition, powder dissolution of RSV cocrystals in different buffer medium containing different surfactants were conducted, and the result revealed that PVP K30 is an effective surfactant to maintain the supersaturation. Then pharmacokinetic experiments suggested that RSV cocrystals showed shorter <i>T</i>_max, and RSV–NA exhibited higher <i>C</i>_max and AUC_0–24 values. Furthermore, RSV cocrystals exhibited superior mechanical properties compared to RSV pure component. These results may provide an alternative formulation for RSV

Preparation and Solid-State Characterization of Dapsone Drug–Drug Co-Crystals

Pharmaceutical co-crystals involving two active pharmaceutical ingredients are rarely revealed in the literature. In this work, crystal engineering principles were exercised to guide the design and synthesis of the Biopharmaceutics Classification System class IV drug dapsone (DAP). We reported six drug–drug co-crystals of DAP with sulfanilamide, flavone, luteolin, caffeine in 1:1 stoichiometry, caffeine in 1:2 stoichiometry, and 2­(3<i>H</i>)-benzothiazolone. Bioactive coformers were deliberately selected. The resulting co-crystals were fully characterized by a range of analytical technologies, including X-ray powder diffraction, Fourier transform infrared spectroscopy, polarized light microscopy, differential scanning calorimetry, and thermogravimetric analysis, etc. Single-crystal structure analysis reveals that reoccurring supramolecular synthons are observed in different DAP co-crystals. Equilibrium solubility and intrinsic dissolution rates were also compared with those of the parent drug. This work expands the pharmaceutically acceptable solid forms of DAP and supplements the successful cases of drug–drug co-crystals

Preparation and Solid-State Characterization of Dapsone Drug–Drug Co-Crystals

Pharmaceutical co-crystals involving two active pharmaceutical ingredients are rarely revealed in the literature. In this work, crystal engineering principles were exercised to guide the design and synthesis of the Biopharmaceutics Classification System class IV drug dapsone (DAP). We reported six drug–drug co-crystals of DAP with sulfanilamide, flavone, luteolin, caffeine in 1:1 stoichiometry, caffeine in 1:2 stoichiometry, and 2­(3<i>H</i>)-benzothiazolone. Bioactive coformers were deliberately selected. The resulting co-crystals were fully characterized by a range of analytical technologies, including X-ray powder diffraction, Fourier transform infrared spectroscopy, polarized light microscopy, differential scanning calorimetry, and thermogravimetric analysis, etc. Single-crystal structure analysis reveals that reoccurring supramolecular synthons are observed in different DAP co-crystals. Equilibrium solubility and intrinsic dissolution rates were also compared with those of the parent drug. This work expands the pharmaceutically acceptable solid forms of DAP and supplements the successful cases of drug–drug co-crystals

Hydroxyl-Functionalized Ionic Liquid Promoted CO₂ Fixation According to Electrostatic Attraction and Hydrogen Bonding Interaction

The mechanism of cycloaddition reaction between carbon dioxide and epoxide, catalyzed by HEMIMC (1-(2-hydroxyl-ethyl)-3-methylimidazolium chloride), was investigated using the DFT (density functional theory) method. In the presence of HEMIMC, the reaction mechanism changed from single-step to multipath. Seven reaction pathways are reported here, including two steps, epoxide ring-opening and ring-closure of cyclic carbonate, or three main steps, epoxide ring-opening, carbon dioxide insertion, and ring-closure of cyclic carbonate. The catalytic activity of HEMIMC was studied, and the catalytic mechanism was elucidated. The nucleophilic attack of anion and hydrogen bond are two of the most important factors to promote the cycloaddition reaction, especially the OH functional group in HEMIMC. Finally, the influence of different anions on the catalytic activity was investigated

Temperature-Controlled Reaction–Separation for Conversion of CO₂ to Carbonates with Functional Ionic Liquids Catalyst

Carboxylic acid-based ionic liquids (CAILs) were designed and synthesized. They displayed temperature-dependent dissolution–precipitation transitions in propylene carbonate (PC) by controlling the chain length of the carboxyl group. It was found that it could be attributed to the temperature-controlled hydrogen-bond formation/broken between the CAILs components and PC by NMR investigations and DFT calculations. Such a unique phase behavior was successfully utilized for the cycloaddition reaction of CO₂ with epoxides. Due to the activation of epoxide assisted by the hydrogen bond, the optimal ILs could show a 92% yield of PC within 20 min and quickly precipitate out from a homogeneous system at room temperature for easy recycling. The reversible phase transition phenomenon supplied an efficient way to combine activity and recovery of homogeneous catalysts, which is a benefit for energy-saving and industrial applications

Rodlike Micelle Structure and Formation of Ionic liquid in Aqueous Solution by Molecular Simulation

Ionic liquids (ILs) have been used in an enormous number of chemical and biological processes. In recent years, self-assembly of ILs into the micelles has attracted much attention and proved to be the key feature in interpreting many physical phenomena and have influence on fluids transport. Micelles or aggregates are mostly reported to be quasi-spherical objects with the alkyl tails forming the core and the imidazolium headgroups exposed to water. In this work, the formation and structure of rodlike micelle in [C₁₂mim]Br aqueous solution was studied by molecular dynamics simulations based on the united-atom force field. Several separate simulations were performed using both liquid droplet and random-like starting conditions, and self-assembly of cations into the rodlike micelle was observed, which is consistent with the TEM result. A more detailed analysis and comparison between the solution and neat IL using radial distribution functions demonstrate the influencing factors of the micelles, the structure, and interaction between ions and water. Besides, the intermolecular energy and hydrogen-bond number and pattern were also analyzed to further reveal the nature of the micelles

Choropleth map of empirical Bayes estimates of relative risk of Japanese encephalitis in Sichuan province in 2009.

<p>Choropleth map of empirical Bayes estimates of relative risk of Japanese encephalitis in Sichuan province in 2009.</p

SEN and PPV of test statistics based on the Poisson and the Hypergeometric models.

<p>P: Denote the test statistic based on the Poisson probability model.</p><p>H: Denote the test statistic based on the Hypergeometric probability model.</p><p>◊: Denote that the test statistic based on the Poisson model performs better.</p>*<p>: Denote that the test statistic based on the Hypergeometric model performs better.</p