Biological Evaluation of Secondary Metabolites from the Root of Machilus obovatifolia

Bioassay‐guided fractionation of the root of Machilus obovatifolia led to the isolation of four new lignans, epihenricine B ( 1 ), threo‐(7′R,8′R) and threo‐(7′S,8′S)‐methylmachilusol D ( 2 and 3 ), and isofragransol A ( 4 ), along with 23 known compounds. The compounds were obtained as isomeric mixtures (i.e., 2 / 3 and 4 / 20 , resp.). The structures were elucidated by spectral analyses. Among the isolates, 1 , licarin A ( 12 ), guaiacin ( 14 ), (±)‐syringaresinol ( 21 ), and (?)‐epicatechin ( 23 ) showed ABTS (=2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) cation radical‐scavenging activity, with SC₅₀ values of 11.7±0.5, 12.3±1.1, 11.0±0.1, 10.6±0.3, and 9.5±0.2 μM in 20 min, respectively. In addition, kachirachirol B ( 17 ) showed cytotoxicity against the NCI‐H460 cell line with an IC₅₀ value of 3.1 μg/ml.     

Mechanically Recoverable and Highly Efficient Perovskite Solar Cells: Investigation of Intrinsic Flexibility of Organic–Inorganic Perovskite

Highly efficient solar cells with sustainable performance under severe mechanical deformations are in great demand for future wearable power supply devices. In this regard, numerous studies have progressed to implement flexible architecture to high‐performance devices such as perovskite solar cells. However, the absence of suitable flexible and stretchable materials has been a great obstacle in the replacement of largely utilized transparent conducting oxides that are limited in flexibility. Here, a shape recoverable polymer, Noland Optical Adhesive 63, is utilized as a substrate of perovskite solar cell to enable complete shape recovery of the device upon sub‐millimeter bending radii. The employment of stretchable electrodes prevents mechanical damage of the perovskite layer. Before and after bending at a radius of 1 mm, power conversion efficiency (PCE) is measured to be 10.75% and 10.4%, respectively. Additionally, the shape recoverable device demonstrates a PCE of 6.07% after crumpling. The mechanical properties of all the layers are characterized by nanoindentation. Finite element analysis reveals that the outstanding flexibility of the perovskite layer enables small plastic strain distribution on the deformed device. These results clearly demonstrated that this device has great potential to be utilized in stretchable power supply applications.     

Angelica gigas Nakai and Soluplus-Based Solid Formulations Prepared by Hot-Melting Extrusion: Oral Absorption Enhancing and Memory Ameliorating Effects

Oral solid formulations based on Angelica gigas Nakai (AGN) and Soluplus were prepared by the hot-melting extrusion (HME) method. AGN was pulverized into coarse and ultrafine particles, and their particle size and morphology were investigated. Ultrafine AGN particles were used in the HME process with high shear to produce AGN-based formulations. In simulated gastrointestinal fluids (pH 1.2 and pH 6.8) and water, significantly higher amounts of the major active components of AGN, decursin (D) and decursinol angelate (DA), were extracted from the HME-processed AGN/Soluplus (F8) group than the AGN EtOH extract (ext) group (p < 0.05). Based on an in vivo pharmacokinetic study in rats, the relative oral bioavailability of decursinol (DOH), a hepatic metabolite of D and DA, in F8-administered mice was 8.75-fold higher than in AGN EtOH ext-treated group. In scopolamine-induced memory-impaired mice, F8 exhibited a more potent cognitive enhancing effect than AGN EtOH ext in both a Morris water maze test and a passive avoidance test. These findings suggest that HME-processed AGN/Soluplus formulation (F8) could be a promising therapeutic candidate for memory impairment.     

Parental Use of Corporal Punishment in Europe: Intersection between Public Health and Policy

Studies have linked the use of corporal punishment of children to the development of mental health disorders. Despite the recommendation of international governing bodies for a complete ban of the practice, there is little European data available on the effects of corporal punishment on mental health and the influence of laws banning corporal punishment. Using data from the School Children Mental Health Europe survey, the objective of this cross-sectional study was to examine the prevalence and legal status of corporal punishment across six European countries and to evaluate the association between parental use of corporal punishment and children’s mental health. The study found that odds of having parents who reported using occasional to frequent corporal punishment were 1.7 times higher in countries where its use is legal, controlling for socio-demographic factors. Children with parents who reported using corporal punishment had higher rates of both externalized and internalized mental health disorders.     

LSD1 Overexpression Is Associated with Poor Prognosis in Basal-Like Breast Cancer,and Sensitivity to PARP Inhibition

LSD1, a lysine-specific histone demethylase, is overexpressed in several types of cancers and linked to poor outcomes. In breast cancer, the significance of LSD1 overexpression is not clear. We have performed an in silico analysis to assess the relationship of LSD1 expression to clinical outcome. We demonstrate that LSD1 overexpression is a poor prognostic factor in breast cancer, especially in basal-like breast cancer, a subtype of breast cancer with aggressive clinical features. This link is also observed in samples of triple negative breast cancer. Interestingly, we note that overexpression of LSD1 correlates with down-regulation of BRCA1 in triple negative breast cancer. This phenomenon is also observed in in vitro models of basal-like breast cancer, and is associated with an increased sensitivity to PARP inhibitors. We propose therefore that high expression levels of the demethylase LSD1 is a potential prognostic factor of poor outcome in basal-like breast cancer, and that PARP inhibition may be a therapeutic strategy of interest in this poor prognostic subtype with overexpression of LSD1.     

Initial Experience with a Wireless Ultrasound-Guided Vacuum-Assisted Breast Biopsy Device

Objective

To determine the imaging characteristic of frequent target lesions of wireless ultrasound (US)-guided, vacuum-assisted breast biopsy (Wi-UVAB) and to evaluate diagnostic yield, accuracy and complication of the device in indeterminate breast lesions.

Materials and Methods

From March 2013 to October 2014, 114 women (age range, 29–76 years; mean age, 50.0 years) underwent Wi-UVAB using a 13-gauge needle (Mammotome Elite^®; Devicor Medical Products, Cincinnati, OH, USA). In 103 lesions of 96 women with surgical (n = 81) or follow-up (n = 22) data, complications, biopsy procedure, imaging findings of biopsy targets and histologic results were reviewed.

Results

Mean number of biopsy cores was 10 (range 4–25). Nine patients developed moderate bleeding. All lesions were suspicious on US, and included non-mass lesions (67.0%) and mass lesions (33.0%). Visible calcifications on US were evident in 57.3% of the target lesions. Most of the lesions (93.2%) were nonpalpable. Sixty-six (64.1%) were malignant [ductal carcinoma in situ (DCIS) rate, 61%] and 12 were high-risk lesions (11.7%). Histologic underestimation was identified in 11 of 40 (27.5%). DCIS cases and in 3 of 9 (33.3%) high-risk lesions necessitating surgery. There was no false-negative case.

Conclusion

Wi-UVAB is very handy and advantageous for US-unapparent non-mass lesions to diagnose DCIS, especially for calcification cases. Histologic underestimation is unavoidable; still, Wi-UVAB is safe and accurate to diagnose a malignancy.     

Phenotypic and Genetic Characterization of Avian Influenza H5N2 Viruses with Intra- and Inter-Duck Variations in Taiwan

Background

Human infections with avian influenza viruses (AIVs) have frequently raised global concerns of emerging, interspecies-transmissible viruses with pandemic potential. Waterfowl, the predominant reservoir of influenza viruses in nature, harbor precursors of different genetic lineages that have contributed to novel pandemic influenza viruses in the past.

Methods

Two duck influenza H5N2 viruses, DV518 and DV413, isolated through virological surveillance at a live-poultry market in Taiwan, showed phylogenetic relatedness but exhibited different replication capabilities in mammalian Madin-Darby Canine Kidney (MDCK) cells. This study characterizes the replication properties of the two duck H5N2 viruses and the determinants involved.

Results

The DV518 virus replicated more efficiently than DV413 in both MDCK and chicken DF1 cells. Interestingly, the infection of MDCK cells by DV518 formed heterogeneous plaques with great differences in size [large (L) and small (S)], and the two viral strains (p518-L and p518-S) obtained from plaque purification exhibited distinguishable replication kinetics in MDCK cells. Nonetheless, both plaque-purified DV518 strains still maintained their growth advantages over the plaque-purified p413 strain. Moreover, three amino acid substitutions in PA (P224S), PB2 (E72D), and M1 (A128T) were identified in intra-duck variations (p518-L vs p518-S), whereas other changes in HA (N170D), NA (I56T), and NP (Y289H) were present in inter-duck variations (DV518 vs DV413). Both p518-L and p518-S strains had the N170D substitution in HA, which might be related to their greater binding to MDCK cells. Additionally, polymerase activity assays on 293T cells demonstrated the role of vRNP in modulating the replication capability of the duck p518-L viruses in mammalian cells.

Conclusion

These results demonstrate that intra-host phenotypic variation occurs even within an individual duck. In view of recent human infections by low pathogenic AIVs, this study suggests possible determinants involved in the stepwise selection of virus variants from the duck influenza virus population which may facilitate inter-species transmission.