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Effects of alloying Nb with Mo on the structure and hydrogen permeation properties of Nb metal have been investigated by XRD analysis, PCT measurements, and three-point bending tests. The results indicate that all the as-prepared Nb 100-x Mo x (x = 2, 7, 14) alloy samples are Nb-based solid solutions with a BCC structure, which are hydrogenated into their corresponding hydrides with the NbH 0.95 phase after interaction with hydrogen. The lattice deformations of the BCC structure and NbH 0.95 phase are due to the difference in size between Nb and Mo atoms. The Nb 86 Mo 14 sample has a higher hydrogen-diffusion coefficient value (1.84 × 10 −9 cm/s), higher hydride-formation enthalpies (- 35.8 kJ/(mol·H 2 )) with the maximum force and displacement before/after the hydrotreatment, indicating that alloying with Mo can greatly improve the hydrogen-diffusion behavior and anti-bending properties of Nb metal. [ABSTRACT FROM AUTHOR]

Two natural unsaturated fatty acids with aspargyl protease inhibition activity were synthesized for the first time. The stereogenic centers were installed by using Brown asymmetric allylation or chiral building blocks derived from d -glucose, respectively. The conjugate diene unit was introduced via an HWE reaction. The geometry of the C C double bonds was clearly shown to be ( E ) by 1 H NMR in C 6 D 6 . The spectroscopic data for the synthetic samples were in excellent consistency with those reported for the corresponding natural ones. The optical rotations were also compatible with those for the natural ones. The absolute configurations for natural YF-0200R A and B thus could be reliably assigned as (8 S ) and (8 S ,10 S ), respectively. [ABSTRACT FROM AUTHOR]

Epothilone B (Epo B) is a potent antitumor natural product with sub-nanomolar anti-proliferation action against several human cancer cells. However, poor selectivity to tumor cells and unacceptable therapeutic windows of Epo B and its analogs are the major obstacles to their development into clinical drugs. Herein, we present self-assembled nanomicelles based on an amphiphilic carbohydrate-Epo B conjugate that is inactive until converted to active Epo B within the tumor. Four Epo B-Rhamnose conjugates linked via two linkers containing a disulfide bond that is sensitive to GSH were synthesized. Conjugate 34 can self-assemble into nanomicelles with a high concentration of Rha on the surface, allowing for better tumor targeting. After internalization by cancer cells, the disulfide bond can be cleaved in the presence of high levels of GSH to release active Epo B, thereby exhibiting significant anticancer efficiency and selectivity in vitro and in vivo. [Display omitted] • Provide a carbohydrate-drug conjugate nanoagent (CDCN) with well-defined structure. • CDCN provides a way to improve the safety of Epothilone B. • CDCN 34 shows rapid release of Epothilone B in tumor microenviroment. • CDCN 34 shows significant anti-tumor effect in vivo and in vitro. [ABSTRACT FROM AUTHOR]

− Seven previously undescribed ent -eudesmane sesquiterpenoids (1 – 7), as well as seven known analogs (8 – 14), were isolated from the Chinese liverwort Chiloscyphus polyanthus var. rivularis. Their structures were established based on comprehensive spectroscopy analysis, electronic circular dichroism calculations, as well as biosynthetic considerations. The cytotoxicity against HepG2 (Human hepatocellular carcinomas) cancer cell line, and antifungal activity against Candida albicans SC5314 of all isolated ent -eudesmane sesquiterpenoids were preliminarily tested, results showed that the tested compounds did not display obvious cytotoxicity and antifungal activities under the tested concentration. Seven undescribed ent -eudesmanes were isolated and identified from C. polyanthus. Structures were determined by extensive spectroscopic analyses. The cytotoxicity and antifungal activity of all compounds were preliminarily tested. [Display omitted] • Seven undescribed ent -eudesmanes were isolated and identified from C. polyanthus. • Structures were determined by extensive spectroscopic analyses. • The cytotoxicity and antifungal activity of all compounds were preliminarily tested. [ABSTRACT FROM AUTHOR]

Three unprecedented ent -labdane and pallavicinin based dimers pallamins A–C formed via [4 + 2] Diels-Alder cycloaddition, together with eight biosynthetically related monomers were isolated from Pallavicinia ambigua. Their structures were determined by the extensive analysis of HRESIMS and NMR spectra. The absolute configurations of the labdane dimers were determined by single crystal X-ray diffraction of the homologous labdane units, and 13C NMR and ECD calculations. Moreover, a preliminary evaluation of the anti-inflammatory activities of the isolated compounds was performed using the zebrafish model. Three of the monomers demonstrated significant anti-inflammatory activity. Three unprecedented ent -labdane and pallavicinin based dimers pallamins A–C, formed via a [4 + 2] Diels-Alder cycloaddition, were isolated from Pallavicinia ambigua. Their structures were elucidated by extensive analysis of HRESIMS and NMR spectra and theoretical calculations. [Display omitted] • Three labdane dimers and eight labdanes were isolated from Pallavicinia ambigua. • Dimers were formed via [4 + 2] Diels-Alder cycloaddition between two labdane units. • The absolute configurations were determined by X-ray analysis and ECD calculations. • Three labdanes displayed anti-inflammatory activity based on the zebrafish model. [ABSTRACT FROM AUTHOR]

• Children carrying CYP3A5*3 with higher body weight had a higher C 0 /Dose. • Routine CYP3A5 genotyping test played a minor role in <6-year-old pediatric patients. • Exposure levels (C 0 , 2–7 ng/mL) was sufficient to maintain remission status in children with RNS. Tacrolimus, an immunosuppressive drug, was recommended by the 2012 KDIGO guidelines to treat nephrotic syndrome (NS) in children and adults. However, it has high interpatient pharmacokinetic variability and exposure levels should be monitored, although there are no specified target concentrations. This retrospective study aimed to review efficacy and safety after concomitant treatment with tacrolimus and prednisone, and to identify factors that contribute to the variable blood-trough-concentration-to-dose (C 0 /Dose) ratio in children with refractory NS (RNS). A 6-month therapy induced complete or partial remission in 95% of patients. One-year follow-up indicated a high remission rate and low nephrotoxicity. Under maintenance dosages, approximately 95% of the C 0 values were 2–7 ng/mL. Body weight (BW), age, CYP3A5 polymorphisms were the factors affecting the C 0 /Dose ratio. The C 0 /Dose ratio in patients with a BW of <20 kg was 1.5-fold than that in patients with BW of ≥40 kg. Moreover, the C 0 /Dose ratio in patients aged 1–≤6 and 6–≤12 years was significantly lower than that in patients aged 12–≤18 years, by 25% and 48%, respectively. There were no significant association between CYP3A5 genotyping and C 0 /Dose ratio in younger children (1–≤6 years), rather than older children (6–≤18 years). In conclusion, routine CYP3A5 genotyping should be considered in children aged over 6 years and exposure levels (C 0) of 2–7 ng/mL may be feasible when tacrolimus is combined with low-dose prednisone to treat childhood RNS. [ABSTRACT FROM AUTHOR]