Photo-/Electrocatalytic Difunctionalization of Alkenes Enabled by C-H Radical Functionalization.

The difunctionalization of alkenes represents a powerful tool to incorporate two functional groups into the alkene bones for increasing molecular complexity and has been widely utilizations in chemical synthesis. Upon the catalysis of the green, sustainable, mild photo-/electrochemistry technologies, much attentions have been attracted to the development of new tactics for the transformations of the important alkene and alkane feedstocks driven by C-H radical functionalization. Herein, we summarize recent advances in the photo-/electrocatalytic difunctionalization of alkenes enabled by C-H radical functionalization. We detailedly discuss the substrate scope and the mechanisms of the photo-/electrocatalytic alkene difunctionalization reactions by selecting impressive synthetic examples, which are divided into four sections based on the final terminated step, including oxidative radical-polar crossover coupling, reductive radical-polar crossover coupling, radical-radical coupling, and transition-metal-catalyzed coupling.

20(S)-25-methoxyl-dammarane-3ß, 12ß, 20-triol negatively regulates activation of STAT3 and ERK pathways and exhibits anti-cancer effects in HepG2 cells.

The pro-inflammatory cytokine interleukin 6 (IL-6), via activating its downstream JAK/STAT3 and Ras/ERK signaling pathways, is involved in cell growth, proliferation and anti-apoptotic activities in various malignancies. To screen inhibitors of IL-6 signaling, we constructed a STAT3 and ERK dual-pathway responsive luciferase reporter vector (Co.RE). Among several candidates, the natural compound 20(S)-25-methoxyl-dammarane-3ß, 12ß, 20-triol (25-OCH3-PPD, GS25) was identified to clearly inhibit the luciferase activity of Co.RE. GS25 was confirmed to indeed inhibit activation of both STAT3 and ERK pathways and expression of downstream target genes of IL-6, and to predominantly decrease the viability of HepG2 cells via induction of cell cycle arrest and apoptosis. Interestingly, GS25 showed preferential inhibition of HepG2 cell viability relative to normal liver L02 cells. Further investigation showed that GS25 could not induce apoptosis and block activation of STAT3 and ERK pathways in L02 cells as efficiently as in HepG2 cells, which may result in differential effects of GS25 on malignant and normal liver cells. In addition, GS25 was found to potently suppress the expression of endogenous STAT3 at a higher concentration and dramatically induce p38 phosphorylation in HepG2 cells, which could mediate its anti-cancer effects. Finally, we demonstrated that GS25 also inhibited tumor growth in HepG2 xenograft mice. Taken together, these findings indicate that GS25 elicits its anti-cancer effects on HepG2 cells through multiple mechanisms and has the potential to be used as an inhibitor of IL-6 signaling. Thus, GS25 may be developed as a treatment for hepatocarcinoma with low toxicity on normal liver tissues as well as other inflammation-associated diseases.

TRP14 promotes resistance to cisplatin by inducing autophagy in ovarian cancer.

Cisplatin is a common chemotherapeutic agent against ovarian cancer; however, drug resistance is a major limiting factor for its use in clinical treatment. The underlying mechanisms of cisplatin resistance in ovarian cancer have not yet been fully elucidated. Thus, this study aimed to elucidate some of the mechanisms responsible for resistance to cisplatin in ovarian cancer. The results demonstrated that the cisplatin­resistant human ovarian cancer cell lines, SKOV3/DDP and A2780/DDP, exhibited higher autophagy levels than the control ovarian cancer cell lines, SKOV3 and A2780. Moreover, autophagy inhibition by 3­methyladenine or shRNA against autophagy­related gene (ATG)5 potentiated the cytotoxicity induced by cisplatin, whereas autophagy induction by rapamycin (Rapa) increased cell survival. Exposure to cisplatin induced an upregulation in the expression of thioredoxin­related protein of 14 kDa (TRP14). Furthermore, TRP14 knockdown or overexpression decreased or increased the autophagy response and cisplatin resistance, and this effect was reversed by treatment with Rapa or ATG5 knockdown. The findings of this study also suggested that TRP14 induced autophagy and chemoresistance via the 5'AMP­activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/p70S6K signaling pathway. Importantly, the data from a tissue array revealed a positive association between TRP14 and Beclin1 in human ovarian cancer and marginal tissues. These findings have identified, for the first time, to the best of our knowledge, that TRP14 induces autophagy and consequently cisplatin resistance in ovarian cancer cells via the AMPK/mTOR/p70S6K signaling pathway. This in turn renders TRP14 as a potential predictor or target in ovarian cancer therapy.

Experimental study on the location of an acoustic emission source considering refraction in different media.

The existing acoustic emission (AE) source location methods assume that acoustic waves propagate along straight lines, and the source location is determined by average wave velocity. Because of the heterogeneity of materials, location results often fail to meet the accuracy requirement. For this reason, an AE source location method considering refraction in different media was proposed in this paper. According to sensor coordinates, the arrival time of acoustic waves, the velocities of acoustic waves in two kinds of media, the space-time relation equations of the AE source point and the measuring point were established by the precise coordinates of the AE source based on Snell's law. The feasibility of the algorithm was verified by experiments, and the factors influencing location accuracy were also analysed. The results show that the algorithm proposed in this paper is applicable for both the same medium and different media, and the accuracy of localization is not affected by the ratio of wave velocities in two media or the distance from the AE source to the refraction surface.