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Utilizing the novel salt-loaded hydrogel microspheres, the controlled crystallization of hen egg white lysozyme (HEWL) was accomplished by attaining precipitant-dependent, location-dependent, and time-dependent regulation of supersaturation and nucleation. [Display omitted] • Synthesis of monodispersed PEGDA hydrogel microspheres (HMSs). • HMSs are used as templates loaded with different concentrations of NaCl. • Demonstration of precipitation-dependent, location-dependent, and time-dependent control of the supersaturation by HMSs. • Applications of nucleation and crystal size control by HMSs. Due to their biocompatibility and adjustable chemical structure and morphology, hydrogels have great potential in many applications, and can be used to enhance protein crystal quality and crystallization efficiency, contributing to biomedicine manufacturing. Monodispersed PEGDA hydrogel microspheres (HMSs) were synthesized using a Lego-inspired microfluidic device. The generated droplets were then UV polymerized, partially hydrolyzed with 0.1 M NaOH solution to improve their absorption capacity, and soaked in a buffer solution containing 0, 0.5, 1, 2, and 4 M NaCl. Salt-loaded HMSs were used as the medium for the enhanced crystallization of hen egg white lysozyme from aqueous solutions. Different supersaturations were achieved in the protein solutions by releasing NaCl of different concentrations from HMSs, as confirmed by electrical conductivity measurements. HMSs with or without NaCl can both provide heterogeneous nucleation sites due to their nano-porous structure and wrinkled surface. The addition of NaCl-loaded HMSs to the protein solution can also increase or decrease the supersaturation in the whole solution or locally near the HMS, leading to controllable nucleation time and crystal size distribution dependent on the NaCl concentration loaded into HMSs. [ABSTRACT FROM AUTHOR]

To investigate the nucleation behavior of ammonium sulphate, commonly used as a fertilizer, during cooling crystallization, polythermal methods have been used to determine the metastable zone widths (MSZWs) of ammonium sulphate in aqueous solution from the saturation temperature at 288.15 to 317.15 K under cooling rates of 6.0 to 30.0 K per hour. MSZWs increased with the increasing cooling rate and the saturation temperature. Based on classical nucleation theory, the nucleation potential model linked the MSZWs to the critical nucleation potential and pre-exponential factor. The MSZWs from one saturation temperature or with one cooling rate were used to predict the MSZWs with other saturation temperatures or with other cooling rates, by the nucleation potential model. The estimated MSZWs were compared with the experimental values. Further, according to the characteristics of the electrolyte solution, the supersaturation term in the nucleation potential model was modified by the activity coefficient. The estimated MSZWs showed improved accuracies and a tendency to be positively correlated with both the supersaturation temperature and cooling rate, which was consistent with the experimentally measured MSZWs. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel cocrystal of metformin hydrochloride with citric acid was synthesized and obtained. • Physicochemical properties and the single-crystal structure of the cocrystal were investigated and determined. • The binding models of the cocrystal were built, simulated, and calculated to investigate the mechanisms of cocrystal formation. • Hirshfeld surface of cocrystal was analyzed to reveal the intermolecular interactions and the strength of molecular packing. Pharmaceutical cocrystals have matured into an effective technique for tuning the physicochemical and mechanical properties of drugs in solid form simultaneously. Herein, in order to provide a novel cocrystal form of oral medicine metformin hydrochloride (MH), citric acid (CA) was selected as an efficient ligand after screening a variety of inorganic and organic acids. Thus, based on the principle of crystal engineering, we report a novel cocrystal: metformin hydrochloride - citric acid (MHCA) after the systematic screening, which was experimentally proved to be constituted with 1:1 stoichiometry. Compared with pure MH, MHCA has been proved higher solubility in water, methanol, and ethanol from 283.15 to 313.15 K. Through single-crystal X-ray diffraction (SC-XRD), the particular molecular structure of MHCA has been determined as the orthorhombic system and Pbca space group. Besides, the binding model of MH-CA was built for investigating the binding energy and stability between two components at 278, 298, and 318 K, which were found to be essential for the prediction and analysis of cocrystals. The contribution of different intermolecular interactions and the strength of molecular packing in the cocrystal also have been investigated by Hirshfeld surface analysis. It was found that the cocrystal structure was mainly stabilized by intermolecular hydrogen bonds existing as N—H···O between components, which indicated that the diffusion-combination trend of molecules enhanced the regular array of cocrystal. The results revealed that the molecules of MH and CA formed supramolecular cocrystals mainly induced by hydrogen bonds after passive contacts, such as co-crystallization or grind. [ABSTRACT FROM AUTHOR]

Building smart cities requires three-dimensional (3D) modelling to facilitate the planning and management of built environments. This requirement leads to high demand for data on vertical dimensions, such as building height, that are critical for the construction of 3D city models. Despite increasing recognition of the importance of such data, their acquisition in a low-cost and efficient manner remains a daunting task. Big data, particularly street view images (SVIs), provide an opportunity to efficiently solve this problem. In this study, we aim to derive information on building height from openly available SVIs by using single view metrology. Unlike other methods using multisource inputs, our method capitalizes on deep neural networks to extract a set of features – such as vanishing points, line segments, and semantic segmentation maps – for single view measurement and then estimates the height from single SVIs. The minimal input required by the method increases its competitiveness in large-scale estimation of building heights, especially in areas with difficulty to obtain the conventional remote sensing data. In addition to experiments that demonstrate the effectiveness and efficiency of the proposed method, we also conduct a thorough analysis of uncertainties and errors brought by the method, thereby providing guidance for its future applications. 1 Source code: https://github.com/yzre/SIHE. [ABSTRACT FROM AUTHOR]

• The nucleation behavior of tiamulin hydrogen fumarate methanol solvate (THFMS) was investigated. • The solubility and cosolvency effect of THFMS were studied in methanol-ethyl acetate binary mixtures. • The interfacial energy, the critical nucleation potential, and the critical nucleation parameterswere discussed. To investigate the nucleation behavior of tiamulin hydrogen fumarate methanol solvate (THFMS), the solubility, induction time, and metastable zone width (MSZW) of THFMS in methanol-ethyl acetate binary mixtures were measured. The nucleation potential model, which is based on the classical nucleation theory and correlates the induction time and MSZW, has been employed to deal with the experimental data and estimate the interfacial energy and the critical nucleation potential. The estimated values determined from the nucleation potential model are in accordance with the experimental values. The interfacial energy and the critical nucleation potential of THFMS steadily decrease with the increasing saturation temperature, whereas those of THFMS initially decrease and subsequently increase as the ethyl acetate content increases. The results demonstrate that an increase in saturation temperature leads to enhanced nucleation favorability, while the difficulty of nucleation initially decreases and then increases with increasing ethyl acetate content. Furthermore, the critical nucleation parameters, including the critical Gibbs free energy, the critical nucleus size, and the critical number of molecules in a nucleus, exhibit the same trend in alterations regarding both saturation temperature and ethyl acetate content. [ABSTRACT FROM AUTHOR]

• The nucleation behavior and nucleation kinetics of cinnamic acid were investigated and calculated. • Both the solute–solute and solute–solvent interactions during nucleation process were explored by molecular simulation. • The intrinsic mechanism of different solvents affecting the desolvation process was revealed. In this paper, the induction time and the metastable zone widths (MSZWs) of cinnamic acid in four pure solvents methanol, ethanol, acetone, and ethyl acetate were determined. Driven by the same supersaturation, the induction time is ethyl acetate > methanol > ethanol > acetone in descending order, then the effect of solvent on nucleation was further investigated by model fitting and molecular dynamic (MD) simulation. The MSZWs were fitted with the Nývlt's approach and Modified Sangwal's theory to investigate its nucleation kinetics. The results show that the fitted interfacial energy γ increases with decreasing saturation temperature and increasing cooling rate, which explains why nucleation is more likely to occur at high saturation temperatures and low cooling rates. Also, the pre-exponential factor A exhibits a strong correlation with the solvent and cooling rate. Further calculations of the key nucleation parameters (r crit , Δ G crit , J) show a positive relationship between the critical nucleation radius r crit and the critical Gibbs free energy Δ G crit. The nucleation rate J is equilibrated under the combined constraints of saturation temperature and driving force Δ µ. Finally, the intermolecular forces in the lattice were analyzed using Hirshfeld surface (HS) and 2D fingerprinting to probe the self-assembly process of molecules. And the hydrogen bonding sites between solute and solvent were predicted by molecular electrostatic potential surface (MEPs). The solute–solvent interaction was visualized by radial distribution function (RDF) and then quantified by calculating the interaction energy. The results show that the stronger hydrogen bonding interactions lead to lower nucleation rates, revealing the important role of solute–solute and solute–solvent interactions in solute desolvation and nucleation process. [ABSTRACT FROM AUTHOR]

15 new bromotyrosine‐derived compounds, pseudoceroximes A–E (1–5), pseudocerolides A–E (6–10), 13‐ketohemifistularin 3 (11), and ceratinines J–M (12–15), were isolated from a Pseudoceratina sp. marine sponge collected in the South China Sea. The planar structures of all compounds were established based on extensive NMR spectroscopic analyses and HRESIMS data. Their absolute configurations were assigned by a combination of modified Mosher's method, ECD calculations and a single‐crystal X‐ray diffraction experiment. Pseudoceroximes A–D (1–4) represent the first examples of the oxime‐type bromotyrosine derivatives possessing the 2‐oxazolidone ring. Pseudoceroximes A (1) and B (2) and pseudocerolide C (8) showed antibacterial activity against methicillin‐resistant Staphylococcus aureus ATCC 43300 with MIC values of 5.2–7.1 µm. Additionally, pseudoceroximes B (2) and D (4) exhibited moderate antiproliferative activity against two human glioma cell lines U87MG and U251. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is an idiopathic intestinal disease characterized by chronic inflammation with unknown etiology. Kuijieling decoction is a traditional Chinese Medicine with unique therapeutic efficacy for UC. To validate the effects of Kuijieling decoction on vitamin A metabolism and retinoic acid (RA) production, along with evaluation of its immunomodulatory activity, and further clarify the upstream mechanisms underlying Treg/Th17 regulation that contribute to therapeutic effects against UC. Network pharmacology and molecular docking analyses were employed to predict the potential anti-UC targets of Kuijieling and associated pathways. A rat model of UC was generated by treatment with trinitrobenzene sulfonic acid (TNBS) to induce inflammation. T lymphocytes were induced to differentiate into Th17 via combined stimulation with the cytokines TGF-β1, IL-6 and IL-23. Expression levels of RA/RARα-related factors (RARα, CRABPII, Smad3, IL-6R and IL-23R) and Treg/Th17 cell-related factors (Foxp3, RORγt) were measured via western blot (WB), quantitative real-time PCR (RT-qPCR), and immunohistochemistry analyses. Components of the vitamin A metabolic pathway (vitamin A, retinol, retinoic acid) and Treg/Th17 cell-related cytokines (IL-10, IL-17, IL-21) were evaluated using ELISA. Flow cytometry was performed to determine the percentages of Treg and Th17 cells. The action targets of Kuijieling were significantly associated with T cell activation, Th17 cell differentiation and the immune response. IL-2, IL-6, STAT3 and RARα displayed strong binding affinities with the main components of Kuijieling, suggesting an important role in its therapeutic efficacy. Kuijieling promoted vitamin A metabolism and RA/RARα signaling in UC rats and T lymphocytes. Moreover, Kuijieling effectively regulated the Treg/Th17 cell balance in UC rats and T lymphocytes and relieved inflammation. The protective effect of Kuijieling was weakened after inhibition of the RA/RARα signaling pathway. Kuijieling promotes vitamin A metabolism and RA synthesis, enhances interactions between RA, intracellular binding protein CRABPII and nuclear receptor RARα, and upregulates Smad3 and Foxp3, thus promoting Treg differentiation. Simultaneously, Kuijieling inhibited expression of IL-6R and IL-23R genes and production of RORγt, leading to suppression of Th17 differentiation, and ultimately, reduction of the Th17/Treg cell ratio. [Display omitted] • Ulcerative colitis is an idiopathic intestinal disease characterized by chronic inflammation with unknown etiology. • Kuijieling decoction is a traditional Chinese Medicine with unique therapeutic efficacy for ulcerative colitis. • Kuijieling decoction stimulates vitamin A metabolism and retinoic acid production. [ABSTRACT FROM AUTHOR]

The checkerboard is a frequently used pattern in camera calibration, an essential process to get intrinsic parameters for more accurate information from images. An automatic checkerboard detection method that can detect multiple checkerboards in a single image is proposed. It contains a corner extraction approach using self-correlation and a structure recovery solution using constraints related to adjacent corners and checkerboard block edges. The method utilizes the central symmetric feature of the checkerboard crossings as well as the spatial relationship of neighboring checkerboard corners and the grayscale distribution of their neighboring pixels. Five public datasets are used in the experiments to evaluate the method. Results show high detection rates and a short average runtime of the proposed method. In addition, the camera calibration accuracy also presents the effectiveness of the proposed detection method with reprojected pixel errors smaller than 0.5 pixels. [ABSTRACT FROM AUTHOR]

• The solubility of Favipiravir in twelve solvents was determined and correlated with the Modified Apelblat, λh, NRTL, and Wilson models. • The dissolution order of Favipiravir was revealed by HSP and solvent effect analysis. • MEPS, Hirshfeld surface, and solvation free energy were applied to investigate Intermolecular interactions. • Thermodynamic properties of Favipiravir in twelve solvents were calculated and discussed by van't Hoff equation. The solubility of Favipiravir in twelve pure solvents, including methanol (MeOH), ethanol (EtOH), n-propanol (NPOH), isopropanol (IPOH), n-butanol (NBOH), acetone (DMK), acetonitrile (MeCN), dichloromethane (DCM), N , N -Dimethylformamide (DMF), methyl acetate (MtAC), ethyl acetate (EtAC), butyl acetate (NBAC) was measured by gravimetric method at a temperature range of 293.15 to 333.15 K at 0.1 MPa. The maximum and minimum of Favipiravir solubility were obtained in DMF at 333.15 K (0.02599 mol·mol−1) and MeOH at 293.15 K (0.00147 mol·mol−1), respectively. At 298.15 K, the order of solubility in different solvents is: DMF > NBAC > DMK > MtAC > EtAC > NBOH > DCM > EtOH > NPOH > IPOH > MeCN > MeOH. The Hansen solubility parameter (HSP) was used to analyze the miscibility of Favipiravir in selected solvents. In addition, the solvent effect was studied by analyzing solvent properties, which indicate that the solubility of Favipiravir in selected solvents is influenced by the synergistic effect of multiple factors. The Modified Apelblat model, λh model, NRTL model, and Wilson model were employed to correlate the solubility data, indicating the Apelblat model provides the highest regression accuracy corresponding to the lowest average value of average relative deviation (ARD, 0.017459) and root mean square deviation (RMSD, 0.00012). In order to explain the dissolution behavior of Favipiravir in different solvents, the intermolecular interactions were analyzed by using Hirshfeld surface (HS), Molecular electrostatic potential surface (MEPS), and solvation free energy. The thermodynamic parameters derived from van't Hoff equation including Δ dis G 0 (10.71–16.57 kJ·mol−1), Δ dis H 0 (6.33–18.67 kJ·mol−1), and Δ dis S 0 (−32.77–25.47 J·mol−1·K−1) indicate that the dissolution of Favipiravir is endothermic, entropy-driven or has no driving force, and non-spontaneous. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel cocrystal of lenalidomide with nicotinamide was predicted and synthesized. • Systematic physicochemical properties such as solubility, dissolution and stability were studied. • The anomalous thermal phase transition process of the cocrystal was firstly investigated. Lenalidomide (LDM), widely used for the treatment of transfusion-dependent anaemia, has low oral bioavailability due to its poor aqueous solubility. Herein, we selected nicotinamide (NIC) as a coformer and synthesized a novel pharmaceutical cocrystal: lenalidomide-nicotinamide cocrystal (LNC) with a 1:1 stoichiometric ratio for enhancing the physicochemical properties of LDM, such as solubility and stability. For evaluating the ability to form cocrystal of LDM and NIC, a model of hydrogen-bond propensity (HBP) was utilized to calculate the hydrogen bond formation possibility for every hydrogen bond pair based on the existing structural information in the database. Afterward, solid-state grinding and liquid-assisted grinding methods were conducted to synthesize LNC, which were then characterized using powder X-ray diffraction, thermal and spectroscopic analysis. Besides, in the heating process, an interesting and anomalous phenomenon called thermal phase transition of the cocrystal was firstly observed and visualized by the hot stage microscope. Notably, the second thermal stage controlled by the vapor pressure of NIC was further determined experimentally and theoretically, which means that intermolecular hydrogen bonds gradually break when NIC occurs phase transition (from liquid to gas). Further, the physicochemical stability of cocrystal was proved reliable after being tested under accelerated stability conditions of 40 °C/75% RH for one month. Compared to lenalidomide and their physical mixture (molar ratio of 1:1), the dissolution and solubility of LNC have also been improved. [ABSTRACT FROM AUTHOR]

• Dissolution mechanism of clorsulon was explored by solubility measurement in ten solvents. • Thermodynamic properties were studied by model correlation and molecular dynamic simulation. • The intermolecular interaction was revealed by HSP and KAT-LSER model. The thermodynamic properties of clorsulon were systematically studied through solubility measurement, calculation with modeling and molecular dynamics simulations. The equilibrium solubility of clorsulon in ten organic solvents (methanol, ethanol, n-propanol, n-butanol, iso-butanol, ethylene glycol, dichloromethane, acetonitrile, methyl acetate, ethyl acetate) was measured by employing the dynamic method at the temperature from 293.15 to 333.15 K at 0.1 MPa. Especially, the solubility of clorsulon in ethylene glycol shows extreme sensitivity to temperature due to the dihydroxy structure, which was revealed via analysis of hydrogen bond formation between solvent molecules and solute molecules. Subsequently, the experimental solubility values were correlated well with four thermodynamic models, including the modified Apelblat model, λh equation, van't Hoff equation, and Wilson model, among which the modified Apelblat model gives the best fit. The miscibility of clorsulon-solvents and the solvent effect were explored by analyzing the polarity of solvents, Hansen solubility parameters and KAT-LSER model. The derived thermodynamic parameters showed an endothermic, entropy-driven, and non-spontaneous dissolution process of clorsulon via van't Hoff equation. Through molecular dynamic simulation based on the mechanism of intermolecular interaction, the optimized unit cell structure of clorsulon was established, and the solvation free energies were accurately calculated. The results show that the absolute value of calculated solvation free energy was positively correlated with solubility. [ABSTRACT FROM AUTHOR]

The solubility of dabigatran etexilate mesylate (DEM) Forms I, II, M, and Hemihydrate in pure water, methanol, ethanol, n-propanol, and n-butanol was determined by a dynamic method in the temperature range of 278.15–298.15 K under 0.1 MPa. The measured solubility data were then correlated by the modified Apelblat equation, λh equation, and van't Hoff equation, with the best fitting from the modified Apelblat equation. It is found that the dissolution process of DEM is endothermic, entropy-driven, and non-spontaneous by calculating the thermodynamic properties. Further, the molecular simulation was used to investigate the interaction between solute and solvent molecules. The results show that the absolute value of the solvation free energy of DEM is positively correlated with the experimental solubility. • A systematic solubility of dabigatran etexilate mesylate (DEM) polymorphs in five mono-solvents was firstly measured. • Experimental solubility data were correlated by Modified Apelblat equation, λh equation and van't Hoff equation. • Molecular simulation was performed to reveal the solubility behavior of the same crystal form in different mono-solvents. [ABSTRACT FROM AUTHOR]

[Display omitted] • Draw the phase diagram of BAUR-Ⅰ. • Investigate the effects of cooling rates and urea concentrations on MSZWs. • Analyze the nucleation process by the self-consistent Nývlt-like and classical 3D models. • Explore the activation energy of BAUR-Ⅰ. As an intermediate for preparing sedative drugs, barbituric acid (BA) is often used for anesthesia and hypnosis in clinical practice. Due to the poor solubility of BA, barbituric acid – urea co-crystal (BAUR) was prepared to improve the physicochemical properties and bioavailability of BA. Notely, urea is also required in the production process of BA, so selecting urea as the co-crystal former will not bring additional impurities. BAUR has three forms reported. In this paper, the phase diagram of BAUR-Ⅰ was measured to determine the limit concentration of urea. Further, the nucleation metastable zone experiments were conducted to investigate the effects of cooling rates and urea concentrations during the nucleation. The nucleation process was then simulated using two approaches: the self-consistent Nývlt-like approach and the classical 3D model approach. Combined with the calculation of nucleation activation energy E sat , it can conclude that increasing the concentration of urea widens the metastable region to inhibit the nucleation of form Ⅰ in the cooling crystallization. [ABSTRACT FROM AUTHOR]

Residential greenness was theoretically associated with health-related consumption behaviors concerning the socio-ecological model and restoration environment theory, but empirical studies were limited, especially in high-density cities. We examined the associations of residential greenness with unhealthy consumption behaviors (infrequent breakfast consumption, infrequent fruit consumption, infrequent vegetable consumption, alcohol drinking, binge drinking, cigarette smoking, moderate-to-heavy smoking, and heavy smoking) using street-view and conventional greenness metrics in high-density Hong Kong. This cross-sectional study employed survey data from 1,977 adults and residence-based objective environmental data in Hong Kong. Street-view greenness (SVG) was extracted from Google Street View images using an object-based image classification algorithm. Two conventional greenness metrics were used, including normalized difference vegetation index (NDVI) derived from Landsat 8 remote-sensing images and park density derived from a geographic information system database. In the main analyses, logistic regression analyses together with interaction and stratified models were performed with environmental metrics measured within a 1000-m buffer of residence. A standard deviation higher SVG and NDVI were significantly associated with fewer odds of infrequent breakfast consumption (OR = 0.81, 95% CI 0.71–0.94 for SVG; OR = 0.83, 95% CI 0.73–0.95 for NDVI), infrequent fruit consumption (OR = 0.85, 95% CI 0.77–0.94 for SVG; OR = 0.85, 95% CI 0.77–0.94 for NDVI), and infrequent vegetable consumption (OR = 0.78, 95% CI 0.66–0.92 for SVG; OR = 0.81, 95% CI 0.69–0.94 for NDVI). The higher SVG was significantly associated with less binge drinking and the higher SVG at a 400-m buffer and a 600-m buffer were significantly associated with less heavy smoking. Park density was not significantly associated with any unhealthy consumption behaviors. Some of the above significant associations were moderated by moderate physical activity, mental and physical health, age, monthly income, and marital status. This study highlights the potential beneficial impact of residential greenness, especially in terms of street greenery, on healthier eating habits, less binge drinking, and less heavy smoking. [Display omitted] • Street-view greenness (SVG) and two conventional greenness metrics (NDVI and park density) were used. • SVG and NDVI were associated with breakfast, fruit, and vegetable consumption. • Higher SVG was associated with less binge drinking and less heavy smoking. • Associations were moderated by moderate physical activity, mental and physical health, age, income, and marital status. [ABSTRACT FROM AUTHOR]

[Display omitted] • The induction time and metastable zone width of MET-HCl were measured in four hydroxylic solvents. • Based on the modified Sangwal's theory, the interfacial energy and critical nucleation parameters was calculated and discussed. • The role of solvent in crystal nucleation was investigated with the solvent–solute interaction by DFT method. Metformin hydrochloride (MET-HCl) was applied as a model compound to investigate the nucleation behavior in four hydroxylic solvents based on the experimental and simulated methods. Over 320 induction time experiments were measured in four solvents, and the induction time increased in the order: water < methanol < ethanol < n-propanol. The metastable zone widths were determined with different cooling rates and saturation temperatures. According to classical nucleation theory, the nucleation kinetics and thermodynamic parameters (interfacial energy, critical nucleus size and Gibbs free energy) were estimated. The result indicates that the nucleation rate of MET-HCl in water was highest among four solvents. The density functional theory (DFT) calculation was applied to reveal the solvent–solute interaction in crystal nucleation, showing the binding energies increased in the order: water < methanol < ethanol < n-propanol. The simulation results combined with experimental data suggested that the stronger the interactions of solvent–solute molecules, the more difficult the nucleation becomes. [ABSTRACT FROM AUTHOR]

• Identify and characterize apremilast forms B and E. • Determine the solubility of apremilast polymorphs in three binary solvents. • Analyze thermodynamic property by Wilson, NRTL and UNIQUAC models. • Explore the Gibbs energy of solvation and solute-solvent interaction by molecular simulation. The polymorphism of apremilast has been investigated. Two polymorphs have been identified and characterized by differential scanning calorimeter, fourier transform infrared spectroscopy, and powder X-ray diffractometer. Solubilities of apremilast forms B and E in three binary solvents of methanol-water, acetonitrile-water, and acetonitrile-methanol have been measured using the static method at a temperature ranging from 288.15 K to 328.15 K under standard atmospheric pressure. Subsequently, the solubility data have been analyzed using the Wilson, NRTL, and UNIQUAC thermodynamic models, respectively. Furthermore, the Gibbs energy of solution and the radial distribution function have been calculated using the molecular simulation method to evaluate the dissolution mechanism. The Gibbs energy of solution reveals that the rank of solute-solvent interaction correlated well with solubility order in binary solvent mixtures, and the radial distribution function indicates that weakening of solvent-solvent interaction led to an increase in solubility. [Display omitted] [ABSTRACT FROM AUTHOR]

Solubility is important in designing the delivery of the pharmaceuticals and in designing the crystallization process for purification. It is significant to understand the thermodynamics of the stable polymorph and the metastable polymorphs. Lenalidomide can be used for the treatment of multiple myeloma and myelodysplastic syndromes. The lenalidomide solubility of metastable hydrate forms B and E were determined at 0.1 MPa with phosphoric acid solutions in the temperature ranging from 303.15 to 343.15 K. The solubility increased from 8.00 × 10−6 (B) to 9.99 × 10−3 (E) with the rise of temperature and the concentration of phosphoric acid. The solubility has been correlated by the UNIQUAC model, and the molecular interactions between different components in the solution were estimated. To further explain the solubility and understand the molecular interactions in the solutions, the molecular dynamics simulation was used to calculate lattice energy, solvation free energy, and Gibbs energy of solution during the dissolution process. • Phosphoric acid effectively improves the poor solubility of lenalidomide. • Solubility of lenalidomide polymorph was measured in phosphoric acid solution. • Thermodynamic analyses of polymorph were performed based on UNIQUAC model. • Molecular simulation revealed the solubility data of lenalidomide polymorph. [ABSTRACT FROM AUTHOR]

The RNA-binding protein LIN-28 was first found to control developmental timing in Caenorhabditis elegans. Later, it was found to play important roles in pluripotency, metabolism, and cancer in mammals. Here we report that a low dosage of lin-28 enhanced stress tolerance and longevity, and reduced germline stem/progenitor cell number in C. elegans. The germline LIN-28 -regulated microRNA let-7 was required for these effects by targeting akt-1/2 and decreasing their protein levels. AKT-1/2 and the downstream DAF-16 transcription factor were both required for the lifespan and germline stem cell effects of lin-28. The pathway also mediated dietary restriction induced lifespan extension and reduction in germline stem cell number. Thus, the LIN-28/let-7/AKT/DAF-16 axis we delineated here is a program that plays an important role in balancing reproduction and somatic maintenance and their response to the environmental energy level-a central dogma of the 'evolutionary optimization' of resource allocation that modulates aging. [ABSTRACT FROM AUTHOR]

Solubility of d -glucosamine 2-sulfate sodium salt in water and binary aqueous mixtures with methanol, ethanol or n-propanol were firstly reported from 288.15 K to 318.15 K under 0.1 MPa. The results showed that the solubility of GS in water is about three orders of magnitude higher than its solubility in alcohols, and the solubility increases with increasing temperature and the composition of the alcohols. Thermodynamic properties of d -glucosamine 2-sulfate sodium salt, such as melting temperature, and decomposition temperature were determined by DSC and TGA. The solubility in various pure and binary solvents was correlated and compared by the modified Apelblat equation, Jouyban-Acree model, Wilson model, and NRTL model. Mixing thermodynamic properties, such as the mixing Gibbs energy, mixing enthalpy, and the mixing entropy of d -glucosamine 2-sulfate sodium salt in these solvents were estimated and analyzed. • Solubility of GS at 288.15 K to 318.15 K, increasing with T • Solubility at same temperature: in water > in methanol > in ethanol > in propanol • Composition of alcohols (antisolvent) increased: solubility in mixtures decreased • Modified Apelblat equation, Jouyban-Acree, Wilson, and NRTL model applied • Melting, combining with decomposition, started at 466.15 K. [ABSTRACT FROM AUTHOR]