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Through integration of multiple large database, two oncogenic signatures (YAP conserved and TGFβ‐up signatures) were commonly upregulated in the cancer cell lines with the mesenchymal properties. AXL, the expression of which is highly induced in EMT, contributes the doxorubicin resistance in EMT. Doxorubicin treatment induced YAP‐dependent gene response and promoted AXL expression coordinated with TGFβ‐SMAD4., The acquisition of chemoresistance remains a major cause of cancer mortality due to the limited accessibility of targeted or immune therapies. However, given that severe alterations of molecular features during epithelial‐to‐mesenchymal transition (EMT) lead to acquired chemoresistance, emerging studies have focused on identifying targetable drivers associated with acquired chemoresistance. Particularly, AXL, a key receptor tyrosine kinase that confers resistance against targets and chemotherapeutics, is highly expressed in mesenchymal cancer cells. However, the underlying mechanism of AXL induction in mesenchymal cancer cells is poorly understood. Our study revealed that the YAP signature, which was highly enriched in mesenchymal‐type lung cancer, was closely correlated to AXL expression in 181 lung cancer cell lines. Moreover, using isogenic lung cancer cell pairs, we also found that doxorubicin treatment induced YAP nuclear translocation in mesenchymal‐type lung cancer cells to induce AXL expression. Additionally, the concurrent activation of TGFβ signaling coordinated YAP‐dependent AXL expression through SMAD4. These data suggest that crosstalk between YAP and the TGFβ/SMAD axis upon treatment with chemotherapeutics might be a promising target to improve chemosensitivity in mesenchymal‐type lung cancer.

Covalently functionalized water-soluble FeCo/graphitic shell nanocrystals (f-FeCo/GC NCs) were synthesized via 1,3-dipolar cycloaddition of azomethine ylides generated in situ from sarcosine and glucose. The FeCo core has superparamagnetic properties at room temperature, and the graphitic shell exhibits near-infrared optical absorbance. Acetylation of the hydroxyl groups on the f-FeCo/GC NCs gives doubly functionalized FeCo/GC (ff-FeCo/GC) NCs that are soluble only in organic solvents such as ethyl acetate. The f-FeCo/GC NCs were shown to be excellent T1 or T2 MRI contrast agents. Especially, due to the hydrophilic and compact surface functionalization, f-FeCo/GC NCs exhibit a doubled r1 relaxivity and half r2/r1 ratio compared to those of the non-covalently PL-PEG-functionalized FeCo/GC NCs. This work shows not only the first synthesis of covalently functionalized highly water-soluble metal NCs coated with a single-layered graphitic shell but also for the first time the MR enhancing properties of the covalently functionalized magnetic NCs.

Although loss of Sirt1 leads to chromosome aneuploidy, which accounts for higher tumor susceptibility, the molecular mechanisms remain unclear. Herein, we demonstrate that Sirt1 directly regulates Plk1, of which activity is critical for mitotic progression and spindle dynamics. Depletion or inhibition of Sirt1 significantly perturbs the formation of the mitotic spindle, leading to defective chromosome segregation. Elevated depolymerization of the mitotic spindle following loss of Sirt1 was associated with the deregulation of Plk1 activity. Thus, we conclude that Sirt1 may contribute to a mitotic regulator that controls spindle dynamics through Plk1 activity, resulting in fine-tuning of Plk1 dependent microtubule dynamics.

Wip1 belongs to the protein phosphatase C (PP2C) family, of which expression is up-regulated by a number of external stresses, and serves as a stress modulator in normal physiological conditions. When overexpressed, premature dephosphorylation of stress-mediators by Wip1 results in abrogation of tumor surveillance, thus Wip1 acts as an oncogene. Previously, the functional regulation of Wip1 in cell-cycle progression by counteracting cellular G1 and G2/M checkpoint activity in response to DNA damage was reported. However, other than in stress conditions, the function and regulatory mechanism of Wip1 has not been fully determined. Herein, we demonstrated that protein regulation of Wip1 occurs in a cell cycle-dependent manner, which is directly governed by APC/C(Cdh1) at the end of mitosis. In particular, we also showed evidence that Wip1 phosphatase activity is closely associated with its own protein stability, suggesting that reduced phosphatase activity of Wip1 during mitosis could trigger its degradation. Furthermore, to verify the physiological role of its phosphatase activity during mitosis, we established doxycycline-inducible cell models, including a Wip1 wild type (WT) and phosphatase dead mutant (Wip1 DA). When ectopically expressing Wip1 WT, we observed a delay in the transition from metaphase to anaphase. In conclusion, these studies show that mitotic degradation of Wip1 by APC/C(Cdh1) is important for normal mitotic progression.

Solar ultra-violet (UV) radiation and the ensuing photo-damage are adverse factors affecting human skin directly exposed to the sun. Stress responses induced by UV radiation (UVR) elicit premature skin ageing (photoageing), resulting in extensive damage to dermal connective tissue. Disruption of the normal dermal structure of skin connective tissue, primarily collagen, impairs a variety of skin functions and is considered to be the main cause of wrinkle formation. Matrix metalloproteases (MMPs) may be responsible for the degradation of collagen and other extracellular matrix proteins, which are major targets for relieving skin photoageing. Herein, we demonstrated that Sirt1, a putative anti-ageing enzyme, reduced MMP-9 transcriptional expression in skin. The known agonists of Sirt1, resveratrol and metformin, also significantly inhibited MMP-9 expression and appeared to protect collagen from degradation after UVR. These studies suggest that the Sirt1 activator could be used as a novel therapeutic agent to delay skin photoageing.

New triterpenes (I) and (II) are isolated from the title plant along with five known triterpenes.

A new series of photospacers has been prepared with different types of crosslinkers to improve elastic recovery. Afunctional crosslinker with six reactive groups demonstrates the best elastic recovery. As the quantity of crosslinker is increased, the elastic recovery also increases, probably due to an increase in the crosslinking density. The use of ADMS EPS® results in high resolution, good uniformity, and high production yield in the liquid-crystal-display (LCD) process. Especially, EPS® improves and solves problems such as viewing angle, crosstalk, and dark spots.