Dichlororesorcinols Produced by a Rhizospheric Fungi of <i>Panax notoginseng</i> as Potential ERK2 Inhibitors

Rhizospheric fungi of medicinal plants are important sources for discovering novel and valuable secondary metabolites with potential pharmaceutical applications. In our research, five new dichlororesorcinols (1–5) and five known metabolites (6–10) were separated from the secondary metabolites of Chaetomium sp. SYP-F6997, which was isolated from the rhizospheric soil of Panax notoginseng. The identification of these compounds was confirmed using various spectroscopic techniques including ESI-MS, UV, IR, NMR and ECD analyses. These findings highlight the potential of rhizospheric fungi as a rich source of novel bioactive compounds. In addition, chiral HPLC was used to successfully separate the enantiomers compound 4 and compound 5, and TDDFT-ECD/optical rotation calculations were used to test their absolute configurations. This is the first report of compounds 1–10 from the genus Chaetomium, and the first report of compounds 1–5 and 7 from the family Chaetomiaceae. We proposed plausible biosynthetic pathways for dichlororesorcinols 1–6 based on their analogous carbon skeleton. These findings provide insights into the biosynthesis of these compounds and expand our understanding of the secondary metabolites produced by Chaetomium sp. SYP-F6997. To evaluate their potential as therapeutic agents, we investigated the cytotoxic activity of all the isolated metabolites against cell lines H9, HL-60, K562, THP-1 and CEM using the MTT method. The new compounds 1 and 2 exhibited significant cytotoxic activities against H9 and CEM, with IC50 values lower than 10 µM. To further explore the potential mechanisms of action, we performed molecular docking studies to investigate the interactions between compounds 1 and 2 with the potential target ERK2. Our results demonstrate that the compounds exhibited strong binding abilities and formed H-bond interactions with ERK2, providing support for their potent antitumor activities and promising potential as lead molecules for the development of antitumor therapeutics

Bilobalide Induces Apoptosis in 3T3-L1 Mature Adipocytes through ROS-Mediated Mitochondria Pathway

Bilobalide exhibits numerous beneficial bioactivities, including neuroprotective, anti-inflammatory, and antioxidant activity. Our previous study demonstrated that bilobalide inhibits adipogenesis and promotes lipolysis. The dose-dependent cytotoxicity was found to be specific to the mature adipocytes only, indicating the potential for regulating apoptosis in them. Herein, we aimed to investigate the apoptotic effects of bilobalide on 3T3-L1 mature adipocytes and elucidate the underlying mechanisms thereof. Flow cytometry analysis (FACS) revealed the pro-apoptotic effects of bilobalide on these cells. Bilobalide induced early apoptosis by reducing the mitochondrial membrane potential (MMP). DNA fragmentation was confirmed using TUNEL staining. Additionally, bilobalide increased the intracellular reactive oxygen species (ROS) levels and activities of Caspases 3/9. Pre-treatment with NAC (an ROS scavenger) confirmed the role of ROS in inducing apoptosis. Moreover, bilobalide up- and down-regulated the expression of Bax and Bcl-2, respectively, at the mRNA and protein expression levels; upregulated the Bax/Bcl-2 ratio; triggered the release of cytochrome c from the mitochondria; and increased the protein expression of cleaved Caspase 3, cleaved Caspase 9, and PARP cleavage. These results support the conclusion that bilobalide induces apoptosis in mature 3T3-L1 adipocytes through the ROS-mediated mitochondrial pathway, and offers potential novel treatment for obesity

<i>Osmanthus fragrans</i> Flavonoid Extract Inhibits Adipogenesis and Induces Beiging in 3T3-L1 Adipocytes

Osmanthus fragrans has a long history of cultivation in Asia and is widely used in food production for its unique aroma, which has important cultural and economic values. It is rich in flavonoids with diverse pharmacological properties, such as antioxidant, anti-tumor, and anti-lipid activities. However, little is known regarding the effects of Osmanthus fragrans flavonoid extract (OFFE) on adipogenesis and pre-adipocyte transdifferentiation. Herein, this research aimed to investigate the effect of OFFE on the differentiation, adipogenesis, and beiging of 3T3-L1 adipocytes and to elucidate the underlying mechanism. Results showed that OFFE inhibited adipogenesis, reduced intracellular reactive oxygen species levels in mature adipocytes, and promoted mitochondrial biogenesis as well as beiging/browning in 3T3-L1 adipocytes. This effect was accompanied by increased mRNA and protein levels of the brown adipose-specific marker gene Pgc-1a, and the upregulation of the expression of UCP1, Cox7A1, and Cox8B. Moreover, the research observed a dose-dependent reduction in the mRNA expression of adipogenic genes (C/EBPα, GLUT-4, SREBP-1C, and FASN) with increasing concentrations of OFFE. Additionally, OFFE activated the AMPK signaling pathway to inhibit adipogenesis. These findings elucidate that OFFE has an inhibitory effect on adipogenesis and promotes browning in 3T3-L1 adipocytes, which lays the foundation for further investigation of the lipid-lowering mechanism of OFFE in vivo in the future

Low-Temperature In Situ Amino Functionalization of TiO ₂ Nanoparticles Sharpens Electron Management Achieving over 21% Efficient Planar Perovskite Solar Cells

Titanium oxide (TiO 2 ) has been commonly used as an electron transport layer (ETL) of regular-structure perovskite solar cells (PSCs), and so far the reported PSC devices with power conversion efficiencies (PCEs) over 21% are mostly based on mesoporous structures containing an indispensable mesoporous TiO 2 layer. However, a high temperature annealing (over 450 °C) treatment is mandatory, which is incompatible with low-cost fabrication and flexible devices. Herein, a facile one-step, low-temperature, nonhydrolytic approach to in situ synthesizing amino-functionalized TiO 2 nanoparticles (abbreviated as NH 2 -TiO 2 NPs) is developed by chemical bonding of amino (-NH 2 ) groups, via TiN bonds, onto the surface of TiO 2 NPs. NH 2 -TiO 2 NPs are then incorporated as an efficient ETL in n-i-p planar heterojunction (PHJ) PSCs, affording PCE over 21%. Cs 0.05 FA 0.83 MA 0.12 PbI 2.55 Br 0.45 (abbreviated as CsFAMA) PHJ PSC devices based on NH 2 -TiO 2 ETL exhibit the best PCE of 21.33%, which is significantly higher than that of the devices based on the pristine TiO 2 ETL (19.82%) and is close to the record PCE for devices with similar structures and fabrication procedures. Besides, due to the passivation of the surface trap states of perovskite film, the hysteresis of current–voltage response is significantly suppressed, and the ambient stability of devices is improved upon amino functionalization. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

9.7%-efficient Sb₂(S,Se)₃ solar cells with a dithieno[3,2-<i>b</i>: 2′,3′-<i>d</i>]pyrrole-cored hole transporting material

An efficient device based on the Sb2(S,Se)3/DTPTHMe-ThTPA heterojunction offers an effective approach to engineer the interfacial carrier transport path for high power conversion efficiency.</p