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6-Mercaptopurine (6-MP) is a clinically important antitumor drug. The commercially available form was provided as monohydrate and belongs to BCS class II category. Co-crystallization screening by reaction crystallization method (RCM) and monitored by powder X-ray diffraction led to the discovery of a new co-crystal formed between 6-MP and isonicotinamide (co-crystal 1 ). Co-crystal 1 was thoroughly characterized by X-ray diffraction, FT-IR and Raman spectroscopy, and thermal analysis. Noticeably, the in vitro and in vivo studies revealed that co-crystal 1 possesses improved dissolution rate and superior bioavailability on animal model. [ABSTRACT FROM AUTHOR]

Abstract: Five new pregnane steroids, toonasterones A (1), B (2), (Z)-aglawone (3), (Z)-toonasterone C (4), and (E)-toonasterone C (5), were isolated from the stem bark of Toona ciliata var. pubescens. Their structures were elucidated by means of detailed spectroscopic (IR, MS, and 2D NMR) analysis, and the stereochemistry of 1 was secured by X-ray diffraction analysis. (Z)-aglawone (3) exhibited moderate inhibitory activity of protein tyrosine phosphatase 1B (PTP1B), a potential drug target for treatment of type-II diabetes and obesity, with an IC50 value of 1.12μg/mL. [Copyright &y& Elsevier]

• This paper first reveals that the weight space of deep learning is not equivalent to its parameter space, and explains in detail how to optimize the deep learning model in a positive scaling invariant space. • This paper first gives a method of self-encoding Canonical Correlation Analysis (Self-encoding CCA) to optimize both self-coding loss and correlation loss in the fine-tuning stage. The quality of medical image segmentation results directly affect disease analysis and diagnosis. Although traditional medical image segmentation methods have achieved certain results, this type of method is not only computationally inefficient, but also difficult to achieve fully automatic segmentation. Deep learning has a good generalization ability, which provides a new technical approach to solve the above problems. However, the following problems exist in the application of deep learning in medical image segmentation: (1) Optimization of deep learning models. The parameters of the existing deep learning model have not been well optimized; it is easy to cause wrong medical image segmentation. (2) Overfitting problem. As the number of deep learning model layers increases, it makes the deep model fit the training data easily, but its generalization performance on the test set will be poor. In view of this, in order to solve the problem of deep learning model optimization, this paper first reveals that the weight space of deep learning is not equivalent to its parameter space, and explains in detail how to optimize the deep learning model in a positive scaling invariant space. The method of mapping the derivative of the base path back to the weight, and analyzed the stochastic optimization algorithm in F space. In addition, to solve the overfitting problem of deep learning models, this paper first gives a method of self-encoding Canonical Correlation Analysis (Self-encoding CCA) to optimize both self-coding loss and correlation loss in the fine-tuning stage. Based on the above ideas, this paper proposes a medical image segmentation algorithm based on positive scaling invariant-self encoding CCA. The experimental results show that the index obtained by the method proposed in this paper is not only improved by a large margin compared with traditional machine learning methods, but also improved to a certain extent compared with other deep learning methods. [ABSTRACT FROM AUTHOR]

Abstract: Expressions for focused Gaussian Schell-model (GSM) beams are derived and used to study the annihilation and subwavelength structures of phase singularities in the focal region, and to compare with the case of fully coherent Gaussian beams. It is found that the truncation parameter δ and normalized coherence length ε both affect the presence and spatial distribution of phase singularities in the focal plane. Additionally, during the creation and annihilation process the saddle point near the phase singularity does not disappear in the focal plane for GSM beams. [Copyright &y& Elsevier]

Four new daphniphyllum alkaloids, namely daphnicalycines A–D (1 – 4), together with nineteen known related ones (5 – 7 and 11 – 26), were isolated from the stems and leaves of Daphniphyllum calycinum. Their structures including the absolute configurations were unambiguously elucidated by extensive spectroscopic analysis, X-ray diffraction analysis and comparison with the reported data. In particular, with the assistance of X-ray diffraction analysis, we were able not only, for the first time, to give full 1H and 13C NMR assignment of daphniteijsmanine (7) and to elucidate its absolute stereochemistry, but also lead to correct the structure of caldaphnidine E (9). The confusions reported for 1 and daphnimacropine (8) in the literature were also clarified. Image 1 • Twenty-three daphniphyllum alkaloids, of which four are new (1 – 4), were isolated from the plant Daphniphyllum calycinum. • The absolute configurations of 1 , 2 and 5 – 7 were unambiguously determined by X-ray diffraction analysis. • The structure of caldaphnidine E (9) was corrected as that of daphniteijsmanine (7). • The confused information regarding the structures of 1 and daphnimacropine (8) in the literature was also clarified. [ABSTRACT FROM AUTHOR]

Perovskite-phase LaCr 1-x Fe x O 3 (0 ≤ x ≤ 0.7) ceramics were fabricated by two-step sintering of powders synthesized by conventional solid-state reaction. XRD patterns reveals that the ceramics are single-phased LaCr 1-x Fe x O 3 solid solution at lower Fe contents, but form a biphasic mixture of LaCrO 3 -LaFeO 3 at higher Fe contents. SEM analysis indicates that Fe doping causes a reduction in porosity, and a corresponding increase in density. The effects of Fe doping on electrical properties have also been investigated. The electrical resistivity ρ 25 °C decreases initially and then increases within a wide range of 634.4–83915.9 Ω·cm with increasing Fe content, whereas B varies within a relatively narrow range of 3651−4301 K. Such combination enables it to be a potential candidate for NTC thermistors. An investigation of elevated-temperature aging behavior shows that the resistance shifts at 25 °C were less than 0.65 % after annealing at 125 °C in air for 1000 h, revealing that the material exhibits excellent stability. [ABSTRACT FROM AUTHOR]

Abstract A series of NTC thermistor ceramics based on LaMn 1-x Ti x O 3 -NiMn 2 O 4 (0≤x≤0.7) composite system have been fabricated by solid-state method. X-ray diffraction analysis indicates the composite ceramics mainly consisting of a rhombohedral perovskite LaMn 1-x Ti x O 3 phase and a cubic spinel NiMn 2 O 4 phase. SEM images show high density of the as-prepared composite ceramics. The effects of the Ti doping and the weight ratio of LaMn 1-x Ti x O 3 /NiMn 2 O 4 on electrical property have been studied. The electrical resistivity ρ increases significantly with Ti addition increasing and decreases obviously with LaMn 1-x Ti x O 3 concentration increasing. The ρ 25 °C and B values are in the range of 3.2–53,200.0Ω·cm and 1300–4008 K, respectively, and could be adjusted to desired values and applied in various fields. The conductive mechanism may be related to the ion migration and the percolation theory. After annealing at 125°C for 1000h, the resistance shifts are less than 0.52%, suggesting good stability of the composite and high potential for NTC thermistor applications. [ABSTRACT FROM AUTHOR]

Abstract Two polymorphs of celastrol were discovered and fully characterized by X-ray powder diffraction, thermogravimetry analysis, and differential scanning calorimetry. The single-crystal structures of form I and the isostructural solvate of form II were disclosed by single-crystal X-ray diffraction. The apparent solubility and wettability of both the crystalline forms were determined. It was found that surfactant can significantly improve the solubility of celastrol up to more than 104 times. Tween 80 and sodium dodecyl sulfate largely improved the wettability of the 2 crystals. Form I shows better wettability than form II in all the buffer solutions with polymers and surfactants. Compared with form II, form I exhibits higher solubility in carboxymethylcellulose and polyvinylpyrrolidone media but much lower solubility in tween 80 and sodium dodecyl sulfate solutions. An investigation of wettability and solubility mechanisms was fully explored, and a hypothesis was proposed to understand the abnormal solubility differences. [ABSTRACT FROM AUTHOR]

Three new scalarane-type sesterterpenes, namely Hyrtiosins H−J (1−3), along with thirteen known related compounds (4−16), were isolated from the South China Sea sponge Hyrtios erecta. Their structures were elucidated by extensive spectroscopic analysis and by the comparison of their spectroscopic data with those reported in the literature. The stereochemistry of heteronemin (9) was determined for the first time by X-ray crystallography study using Cu K α radiation. In bioassay, compound 5 and 10 displayed considerable inhibitory activity against human protein tyrosine phosphatase 1B (PTP1B) enzyme with IC 50 values of 19.68 μM, and 8.81 μM, respectively. [Display omitted] • Sixteen scalarane sesterterpenes, including three new ones, were isolated from the South China Sea Sponge Hyrtios erecta. • The configurations of compounds were determined by extensive spectroscopic analysis and comparison withthe reported data. • Compounds 5 and 10 displayed significant inhibitory activity against human protein tyrosine phosphatase 1B (PTP1B) enzyme. [ABSTRACT FROM AUTHOR]

A series of chiral oxazino-indoles have been synthesized via a key intermolecular oxa-Pictet–Spengler reaction. These compounds exhibited significant and selective neuroprotective effects against Aβ 25–35 -induced neuronal damage. This is the first report of evaluating the influence of chiral diversity of oxazino-indoles on their neuroprotective activities, with the structure–activity relationship been analyzed. The highly active compounds 3f , 3g , 4g , 4h , and 6b all performed over 90% cell protection, providing a new direction for the development of neuroprotective agents against Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Creatine phosphate sodium (CPS) salt is a first-line cardiovascular drug for severe diastolic heart failure. The drug exists in different hydrate forms. The marketed drug form was determined as CPS·4.5H2O (H1); however, the reference standard was supplied as CPS·6H2O (H2). In this work, we present two newly identified hydrate forms: a thermodynamically stable low hydrate form, CPS·1.5H2O (H3), and a pressure-sensitive transit form, CPS·7H2O (H4). The hydrate forms were discovered through a comprehensive solid-state screening experiment and fully characterized using a range of analytical techniques including X-ray powder diffraction (XRPD), FTIR, Raman spectroscopy, hot-stage microscopy (HSM), thermogravimetric analysis, and differential scanning calorimetry. Stability tests revealed that H3 was the most stable hydrate under thermal stimulation. H4 is a pressure-sensitive hydrate and easily transforms to H2 and then H1 upon grinding. The form transformation process was closely monitored using the HSM, variable-temperature XRPD (VT-XRPD), and VT-Raman spectroscopy techniques. Specifically, the transformation of H4 to H1 is characterized in a single-crystal-to-single-crystal transformation process. The newly discovered hydrate form H3 has superior physicochemical properties than the marketed forms and is worthy of further development. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3688-3695, 2014 [ABSTRACT FROM AUTHOR]

[Display omitted] Isotretinoin is the first-line drug for treatment of severe acne. Only one polymorph was reported even though it has been launched for nearly 40 years, and its clinic application was however limited by its stability and solubility challenges. In our study, two new polymorphs of isotretinoin were discovered and fully characterized. The transformation relationships between these solid forms were fully discussed, and a visible color change during single-crystal-to-single-crystal phase transition with the conformational change was investigated. Form II is determined to be thermodynamic stable form at room temperature, but metastable form at body temperature. The results show that form II is an ideal solid state possessing both superior thermal stability (60℃, open air) and higher absorption once delivered into body. The thermal stability can be associated with the crystal structure such as torsion angle. The relative bioavailability of form II is higher than form I as expected, and the bioavailability of form II formulation is about 2 times as that of the marketed form I capsule. Therefore, form II formulation could provide an alternative for better performing isotretinoin. [ABSTRACT FROM AUTHOR]

Five new uncommon cembranoids, named lobophycrasins A–D (1 and 3 – 5) and (−)-humilisin A (2), together with a known related one (6), have been isolated from Hainan soft coral Lobophytum crassum. Their structures were elucidated by extensive spectroscopic analysis, NMR calculation with DP4+ probability analysis, TDDFT-ECD (time-dependent density functional theory-electronic circular dichroism) calculations and comparison with the reported data. Further, with the aid of X-ray diffraction analysis, the structure of lobocrasol (6), which was announced possessing novel unprecedented skeleton, was firmly revised as 6a. In addition, a plausible biogenetic connection among these isolates was also proposed. [Display omitted] • Five new cembranoids have been isolated from Hainan soft coral Lobophytum crassum. • Their structures were elucidated by DP4+ calculation and/or TDDFT-ECD calculation. • With the aid of X-ray diffraction analysis, the structure of lobocrasol (6) was firmly revised as 6a. [ABSTRACT FROM AUTHOR]

d-α-tocopherol (d-αToc), the most biologically active form of natural Vitamin E, is oily in appearance and unstable to oxygen. Esterification and encapsulation are generally needed to stabilize and solidify d-αToc for the purpose of its expanding applications. In this study, we propose a more effective way to stabilize and solidify d-αToc oil in one step. By cocrystallization, the melting point of d-αToc is significantly increased, such that the oily d-αToc is successfully transformed into solid form at room temperature. The single crystal structure of d-αToc was firstly uncovered and the molecular interaction in cocrystals was revealed. Crystalline Vitamin E shows high stability to light and temperature. Its spherical crystallization affords good powder flowability, which is extremely important as food or feed additives. Moreover, cocrystal Vitamin E remains the original form of tocopherol without esterification and thus has a great advantage on higher bioavailability. Cocrystallization of oily d-αToc spares the use of acetic ester and a mass of excipients, which is of great environmental importance and greatly reduces the production cost. [ABSTRACT FROM AUTHOR]