Natural Coumarin Isomers with Dramatically Different AIE Properties: Mechanism and Application.

Aggregation-induced emission luminogens (AIEgens) are of great importance in optoelectronics and biomedical fields. However, the popular design philosophy by combining rotors with traditional fluorophores limits the imagination and structural diversity of AIEgens. Inspired by the fluorescent roots of the medicinal plant Toddalia asiatica, we discovered two unconventional rotor-free AIEgens, 5-methoxyseselin (5-MOS) and 6-methoxyseselin (6-MOS). Interestingly, a slight structural difference of the coumarin isomers leads to completely contrary fluorescent properties upon aggregation in aqueous media. Further mechanism investigation indicates that 5-MOS forms different extents of aggregates with the assistance of protonic solvents, leading to electron/energy transfer, which is responsible for its unique AIE feature, i.e., reduced emission in aqueous media but enhanced emission in crystal. Meanwhile, for 6-MOS, the conventional restriction of the intramolecular motion (RIM) mechanism is responsible for its AIE feature. More interestingly, the unique water-sensitive fluorescence property of 5-MOS enables its successful application for wash-free mitochondria imaging. This work not only demonstrates an ingenious tactic to seek new AIEgens from natural fluorescent species but also benefits the structure design and application exploration of next-generation AIEgens.

In utero di-(2-ethylhexyl) phthalate-induced testicular dysgenesis syndrome in male newborn rats is rescued by taxifolin through reducing oxidative stress.

Testicular dysgenesis syndrome in male neonates manifests as cryptorchidism and hypospadias, which can be mimicked by in utero phthalate exposure. However, the underlying phthalate mediated mechanism and therapeutic effects of taxifolin remain unclear. Di-(2-ethylhexyl) phthalate (DEHP) is the most abundantly used phthalate and can induce testicular dysgenesis syndrome in male rats. To explore the mechanism of DEHP mediated effects and develop a therapeutic drug, the natural phytomedicine taxifolin was used. Pregnant Sprague-Dawley female rats were daily gavaged with 750 mg/kg/d DEHP or 10 or 20 mg/kg/d taxifolin alone or in combination from gestational day 14 to 21, and male pup's fetal Leydig cell function, testicular MDA, and antioxidants were examined. DEHP significantly reduced serum testosterone levels of male pups, down-regulated the expression of SCARB1, CYP11A1, HSD3B1, HSD17B3, and INSL3, reduced the cell size of fetal Leydig cells, decreased the levels of antioxidant and related signals (SOD2 and CAT, SIRT1, and PGC1α), induced abnormal aggregation of fetal Leydig cells, and stimulated formation of multinucleated gonocytes and MDA levels. Taxifolin alone (10 and 20 mg/kg/d) did not affect these parameters. However, taxifolin significantly rescued DEHP-induced alterations. DEHP exposure in utero can induce testicular dysgenesis syndrome by altering the oxidative balance and SIRT1/PGC1α levels, and taxifolin is an ideal phytomedicine to prevent phthalate induced testicular dysgenesis syndrome.

pH-responsive silk fibroin-based CuO/Ag micro/nano coating endows polyetheretherketone with synergistic antibacterial ability, osteogenesis, and angiogenesis.

Polyetheretherketone has been widely used for bone defect repair, whereas failures may happen due to implant loosening and infection. Thus, PEEK implant with multi-function (osteogenesis, angiogenesis, and bacteria-killing) is essential to solve this problem. Herein, copper oxide microspheres (µCuO) decorated with silver nanoparticles (nAg) were constructed on porous PEEK surface via silk fibroin. In vitro studies highlighted the pH controlled release ability of this coating. It liberated a high dose of Cu2+ and Ag+ at low pH environment (pH 5.0), leading to 99.99% killing of planktonic bacteria and complete eradication of sessile bacteria, avoiding biofilm formation. Under physiological environment (pH 7.4), a lower amount of leaked metal ions induced promoted ALP production, collagen secretion, and calcium deposition, as well as NO production, which indicated potentiated osteogenesis and angiogenesis. In vivo results displayed the highest new bone volume around, and the appearance of new bone inside porous structure of, PEEK implant with this coating in rabbit tibia, signified the abilities of this coating to promote bone regeneration and osseointegration. Our study established solid support for implants with this coating to be a successful bone defect repair solution. STATEMENT OF SIGNIFICANCE: In this study, CuO/Ag micro/nano particles were incorporated into the porous surface of PEEK through polydopamine and silk fibroin layers. The design of this coating conferred pH-controlled release behavior to Cu2+ and Ag+. High dose of metal ions were released at pH 5.0, which presented synergistic antibacterial ability and killed 99.99% of planktonic bacteria. Low concentration of metal ions were controlled by this coating at physiological environment, which potentiated osteodifferentiation of Ad-MSC in vitro and led to complete integration of implant with bone tissue in vivo.

13C-lutein is differentially distributed in tissues of an adult female rhesus macaque following a single oral administration: a pilot study.

Despite the growing awareness regarding lutein's putative roles in eyes and brain, its pharmacokinetics and tissue distribution in primates have been poorly understood. We hypothesized that 13C-lutein will be differentially distributed into tissues of an adult rhesus macaque (Macaca mulatta) 3 days following a single oral dose. After a year of prefeeding a diet supplemented with unlabeled lutein (1 µmol/kg/d), a 19-year-old female was dosed with 1.92 mg of highly enriched 13C-lutein. Tissues of a nondosed, lutein-fed monkey were used as a reference for natural abundance of 13C-lutein. On the third day postdose, plasma and multiple tissues were collected. Lutein was quantified by high-performance liquid chromatography-photodiode array detector, and 13C-lutein tissue enrichment was determined by liquid chromatography quadrupole time-of-flight mass spectrometry. In the tissues of a reference monkey, 12C-lutein with natural abundance of 13C-lutein was detectable. In the dosed monkey, highly enriched 13C-lutein was observed in all analyzed tissues except for the macular and peripheral retina, with the highest concentrations in the liver followed by the adrenal gland and plasma. 13C-lutein accumulated differentially across 6 brain regions. In adipose depots, 13C-lutein was observed, with the highest concentrations in the axillary brown adipose tissues. In summary, we evaluated 13C-lutein tissue distribution in a nonhuman primate following a single dose of isotopically labeled lutein. These results show that tissue distribution 3 days following a dose of lutein varied substantially dependent on tissue type.