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In this paper the innovative approach of nano into micro dry powders (NiM) was applied to incorporate into mannitol or mannitol/cysteamine micromatrices ivacaftor-loaded nanoparticles for pulmonary delivery in CF. Nanoparticles composed by a mixture of two polyhydrohydroxyethtylaspartamide copolymers containing loaded with ivacaftor at 15.5% w/w were produced. The nanoparticles were incorporated into microparticles to obtain NiM that were fully characterized in terms of size, morphology, interactions with artificial Cf mucus (CF-AM) as well as for aerodynamic behaviour. Finally the activity of ivacaftor-containing NiM was evaluated by in vitro preliminary experiments. NiM at matrix composed by a mixture of mannitolcysteamine showed greater ability to reduce CF-AM viscosity whereas that based on just mannitol showed better aerodynamic properties with a FPF of about 25%. All produced NiM showed very good cytocompatibility and the released ivacaftor was able to restore the chroride transport in vitro. Press-coated tablets have become an indispensable dosage form in chronotherapeutic drug delivery. Drug release from press-coated tablets has been extensively studied, yet there is little knowledge about their mechanical characteristics. This study aimed to systematically investigate the effects of critical factors on the structure, layer adhesion, and delamination tendency of the tablets. Material elasticity was found to play an important role in determining tablet structure in that excessive elastic mismatch between core and shell materials caused tablet defects during decompression and ejection. Unlike bilayer tablets, the overall strength of press-coated tablets was more affected by binding capacity of coating materials than by the core properties. Shell/core ratio was another factor affecting tablet integrity against external stresses. To mitigate the risk of delamination, poor layer adhesion must be compensated by increasing the coating thickness or enhanced by optimizing the formulation and process (e.g., core plasticity/brittleness, initial core solid fraction, and compression speed). X-ray micro-computed tomography revealed the presence of a shell-core gap and inhomogeneous density distribution within the tablet where the side coat appeared as the least dense and weakest region. These findings will enable the improvement of tablet quality and widen the application of press coating in industrial manufacturing. V.The aim of this paper was to investigate the relevance of isoprostanoids i.e., F2-isoprostanes (F2-IsoPs), F4-neuroprostanes (F4-NeuroPs) and F2-dihomo-isoprostanes (F2-dihomo-IsoPs) in semen quality. Isoprostanoid levels were detected in semen of fertile and infertile men with varicocele or idiopathic infertility. Semen quality was assessed by light microscopy and transmission electron microscopy; the relationships between isoprostanes and semen parameters were also explored. F2-IsoPs levels were significantly different in the varicocele group compared to idiopathic infertile group and fertile men (P less then 0.01 and P less then 0.001 respectively). Moreover, F2-dihomo-IsoP values were significantly higher in varicocele group respect to fertile men (P less then 0.05). No significant statistical differences were found regarding F4-NeuroP concentrations. [https://www.selleckchem.com/ selleck chemicals llc] In the whole population, F2-IsoPs positively correlated with F2-dihomo-IsoPs and both isoprostanoids showed a positive correlation with immaturity and a negative correlation with sperm motility. F2-IsoP levels were positively correlated with the percentage of immaturity in infertile varicocele groups (P less then 0.01) whereas a significant relationship between F4-NeuroP values and the percentage of sperm necrosis was shown in idiopathic infertility group (P less then 0.01). A significant negative correlation of F4-NeuroPs with sperm morphology was detected in infertile varicocele subjects (P less then 0.05). This study suggests that isoprostanoid semen levels appear to be associated with male infertility being related to the sperm quality and confirming the important role of fatty acids profiling in human sperm maturation. The acquired resistance to gefitinib limits its clinical application. Epigallocatechin-3-gallate (EGCG) has been found to enhance the efficacy of gefitinib against resistant. However, the cellular and molecular mechanisms have not been completely illuminated in NSCLC. In this study, a new epigallocatechin gallate derivative (2R,3R-6-methoxycarbonylgallocatechin-3-O-gallate, the following referred to as EGCGD) (1) and three known epigallocatechin gallate compounds including epicatechin-3-O-gallate (2), gallocatechin-3-O-gallate (3) and epigallocatechin-3-O-gallate (4, EGCG) were isolated and identified from Anhua dark tea. The pharmacological studies showed EGCGD was more effective against gefitinib-resistant HCC827-Gef cells compared to that of other three epigallocatechin gallate compounds including EGCG, suggesting that introduction of 6-methoxycarbonyl to EGCG might enhance its antitumor activities. Further study on molecular mechanism showed EGCGD increased the potency of gefitinib against HCC827-Gef cells via suppression of epithelial-Mesenchymal transition (EMT) and dual inhibition of PI3K/mTOR. Six new compounds, periplanetols A&nbsp;-&nbsp;F (1-4, 6 and 7), a compound isolated from natural origin for the first time (5), and nine known ones (8-16) were isolated from the 70% ethanol extract of the whole bodies of Periplaneta americana. Their structures including absolute configurations were unambiguously identified by comprehensive spectroscopic analyses and computational methods. Biological evaluation toward COX-2 inhibition revealed that compounds 1, 2, and 10 could inhibit COX-2 activity with the IC50 values of 768.0&nbsp;nM, 617.7&nbsp;nM, and 599.5&nbsp;nM respectively, indicating their potential in developping novel agents against inflammation related disorders. Four new aspidosperma-type alkaloids, melosuavines J-M (1-4) were isolated from the leaves of Melodinus suaveolens. Their structures with absolute configurations were elucidated by extensive HRESIMS and NMR spectroscopic analysis, as well as ECD calculations and Mosher's method. Their cytotoxic activities against four human cancer cell lines were also evaluated.