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[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]

Biological age (BA) has been proposed to evaluate the aging status instead of chronological age (CA). Our study shows evidence that there might be multiple "clocks" within the whole-body system: systemic aging drivers/clocks overlaid with organ/tissue-specific counterparts. We utilize multi-omics data, including clinical tests, immune repertoire, targeted metabolomic molecules, gut microbiomes, physical fitness examinations, and facial skin examinations, to estimate the BA of different organs (e.g., liver, kidney) and systems (immune and metabolic system). The aging rates of organs/systems are diverse. People's aging patterns are different. We also demonstrate several applications of organs/systems BA in two independent datasets. Mortality predictions are compared among organs' BA in the dataset of the United States National Health and Nutrition Examination Survey. Polygenic risk score of BAs constructed in the Chinese Longitudinal Healthy Longevity Survey cohort can predict the possibility of becoming centenarian. [Display omitted] • Constructing biological ages of organs/systems using multi-omics features • Organs and systems are aging at different rates • Specific biological age could predict disease of corresponding organs • Biological ages of organs and systems have diverse genetic architectures Nie et al. estimate biological ages of organs and systems using 402 multi-omics features from 4,066 individuals and demonstrate several applications. They find that organs and systems are aging at different rates, and biological ages could be utilized for population stratification, mortality prediction, and phenotypes of genetic association studies. [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]

Summary Experimental large-scale screens for drug repositioning are limited by restriction to in vitro conditions and lack of applicability to real human conditions. Here, we developed an in silico screen in human in vivo conditions using a reference of single gene mutations' non-tissue-specific "core transcriptome signatures" (CSs) of 8,476 genes generated from the TCGA database. We developed the core-signature drug-to-gene (csD2G) software to scan 3,546 drug treatment profiles against the reference signatures. csD2G significantly outperformed conventional cell line-based gene perturbation signatures and existing drug-repositioning methods in both coverage and specificity. We highlight this with 3 demonstrated applications: (1) repositioned category of psychiatric drugs to inhibit the TGF-β pathway; (2) antihypertensive calcium channel blockers predicted to activate AMPK and inhibit AKT pathways, and validated by clinical electronic medical records; and (3) 7 drugs predicted and validated to selectively target the AKT-FOXO and AMPK pathways and thus regulate worm lifespan. Graphical Abstract Highlights • Non-tissue-specific core signatures (CSs) were generated for 8,476 human genes • csD2G repositions drugs through drug-gene CS modules and specificity mapping • Calcium blockers predicted to target AKT and AMPK are validated by medical records • Seven drugs were repositioned to selectively target AKT and AMPK and extend lifespan Xu et al. generated core transcriptome signatures representing single-gene mutations for 8,476 human genes from the cancer transcriptomes in the TCGA database and developed a drug-repositioning method to predict high-specificity candidate target genes for 1,938 drugs. Applied to targeting aging pathways, 7 lifespan-extending drugs are found and functionally validated. [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]