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67,639 result(s) for "Y. Chen"
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MiR-520h-mediated FOXC2 regulation is critical for inhibition of lung cancer progression by resveratrol
Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal–epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol—∣miRNA-520h—∣PP2A/C—∣Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.
Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement
Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer’s theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level. Optical trapping is a versatile tool for biomedical applications. Here, the authors use an optofluidic lattice to achieve controllable multi-particle hopping and demonstrate single-bacteria-level screening and measurement of binding efficiency of biological binding agents through particle-enabled bacteria hopping.
Individually addressed entangling gates in a two-dimensional ion crystal
Two-dimensional (2D) ion crystals may represent a promising path to scale up qubit numbers for ion trap quantum information processing. However, to realize universal quantum computing in this system, individually addressed high-fidelity two-qubit entangling gates still remain challenging due to the inevitable micromotion of ions in a 2D crystal as well as the technical difficulty in 2D addressing. Here we demonstrate two-qubit entangling gates between any ion pairs in a 2D crystal of four ions. We use symmetrically placed crossed acousto-optic deflectors (AODs) to drive Raman transitions and achieve an addressing crosstalk error below 0.1%. We design and demonstrate a gate sequence by alternatingly addressing two target ions, making it compatible with any single-ion addressing techniques without crosstalk from multiple addressing beams. We further examine the gate performance versus the micromotion amplitude of the ions and show that its effect can be compensated by a recalibration of the laser intensity without degrading the gate fidelity. Our work paves the way for ion trap quantum computing with hundreds to thousands of qubits on a 2D ion crystal. Quantum gates in 2D ion crystals are more challenging than in 1D. Here, the authors use their 2D ion trap platform and acousto-optical deflectors to demonstrate a 2-qubit gate that can stand the ion micromotion in such configuration.
GSK3β controls epithelial–mesenchymal transition and tumor metastasis by CHIP-mediated degradation of Slug
Glycogen synthase kinase 3 beta (GSK3β) is highly inactivated in epithelial cancers and is known to inhibit tumor migration and invasion. The zinc-finger-containing transcriptional repressor, Slug, represses E-cadherin transcription and enhances epithelial–mesenchymal transition (EMT). In this study, we find that the GSK3β-pSer9 level is associated with the expression of Slug in non-small cell lung cancer. GSK3β-mediated phosphorylation of Slug facilitates Slug protein turnover. Proteomic analysis reveals that the carboxyl terminus of Hsc70-interacting protein (CHIP) interacts with wild-type Slug (wtSlug). Knockdown of CHIP stabilizes the wtSlug protein and reduces Slug ubiquitylation and degradation. In contrast, nonphosphorylatable Slug-4SA is not degraded by CHIP. The accumulation of nondegradable Slug may further lead to the repression of E-cadherin expression and promote cancer cell migration, invasion and metastasis. Our findings provide evidence of a de novo GSK3β-CHIP-Slug pathway that may be involved in the progression of metastasis in lung cancer.
Phosphorylation of paxillin confers cisplatin resistance in non-small cell lung cancer via activating ERK-mediated Bcl-2 expression
Paxillin (PXN) is required for receptor tyrosine kinase-mediated ERK activation, and the activation of the Raf/MEK/ERK cascade has been linked with Bcl-2 expression. We hypothesized that phosphorylation of PXN by the EGFR/Src pathway might contribute to cisplatin resistance via increased Bcl-2 expression. We show that cisplatin resistance was dependent on PXN expression, as evidenced by PXN overexpression in TL-13 and TL-10 cells and PXN knockdown in H23 and CL1-5 cells. Specific inhibitors of signaling pathways indicated that the phosphorylation of PXN at Y118 and Y31 via the Src pathway was responsible for cisplatin resistance. We further demonstrated that ERK activation was also dependent on this PXN phosphorylation. Bcl-2 transcription was upregulated by phosphorylated PXN-mediated ERK activation via increased binding of phosphorylated CREB to the Bcl-2 promoter. A subsequent increase in Bcl-2 levels by a PXN/ERK axis was responsible for the resistance to cisplatin. Animal models further confirmed the findings of in vitro cells indicating that xenograft tumors induced by TL-13-overexpressing cells were successfully suppressed by cisplatin combined with Src or ERK inhibitor compared with treatment of cisplatin, Src inhibitor or ERK inhibitor alone. A positive correlation of phosphorylated PXN with phosphorylated ERK and Bcl-2 was observed in lung tumors from NSCLC patients. Patients with tumors positive for PXN, phosphorylated PXN, phosphorylated ERK and Bcl-2 more commonly showed a poorer response to cisplatin-based chemotherapy than did patients with negative tumors. Collectively, PXN phosphorylation might contribute to cisplatin resistance via activating ERK-mediated Bcl-2 transcription. Therefore, we suggest that Src or ERK inhibitor might be helpful to improve the sensitivity for cisplatin-based chemotherapy in NSCLC patients with PXN-positive tumors.
Observation of topological superconductivity in a stoichiometric transition metal dichalcogenide 2M-WS2
Topological superconductors (TSCs) are unconventional superconductors with bulk superconducting gap and in-gap Majorana states on the boundary that may be used as topological qubits for quantum computation. Despite their importance in both fundamental research and applications, natural TSCs are very rare. Here, combining state of the art synchrotron and laser-based angle-resolved photoemission spectroscopy, we investigated a stoichiometric transition metal dichalcogenide (TMD), 2M-WS 2 with a superconducting transition temperature of 8.8 K (the highest among all TMDs in the natural form up to date) and observed distinctive topological surface states (TSSs). Furthermore, in the superconducting state, we found that the TSSs acquired a nodeless superconducting gap with similar magnitude as that of the bulk states. These discoveries not only evidence 2M-WS 2 as an intrinsic TSC without the need of sensitive composition tuning or sophisticated heterostructures fabrication, but also provide an ideal platform for device applications thanks to its van der Waals layered structure. Topological superconductors are potentially important for future quantum computation, but they are very rare in nature. Here, the authors observe topological surface states acquiring a nodeless superconducting gap with similar magnitude as that of the bulk states in 2M-WS 2 , suggesting an intrinsic topological superconductor.
Meta-analysis shows positive effects of plant diversity on microbial biomass and respiration
Soil microorganisms are key to biological diversity and many ecosystem processes in terrestrial ecosystems. Despite the current alarming loss of plant diversity, it is unclear how plant species diversity affects soil microorganisms. By conducting a global meta-analysis with paired observations of plant mixtures and monocultures from 106 studies, we show that microbial biomass, bacterial biomass, fungal biomass, fungi:bacteria ratio, and microbial respiration increase, while Gram-positive to Gram-negative bacteria ratio decrease in response to plant mixtures. The increases in microbial biomass and respiration are more pronounced in older and more diverse mixtures. The effects of plant mixtures on all microbial attributes are consistent across ecosystem types including natural forests, planted forests, planted grasslands, croplands, and planted containers. Our study underlines strong relationships between plant diversity and soil microorganisms across global terrestrial ecosystems and suggests the importance of plant diversity in maintaining belowground ecosystem functioning. The effect of plant biodiversity on microbial function has been tested in limited studies and is likely to be context-dependent. In this meta-analysis of 106 prior studies comparing plant monocultures to mixtures, the authors find that plant diversity increases microbial biomass and respiration rates, an effect moderated by stand age.