Observation of a Photonic Orbital Gauge Field.

Gauge field is widely studied in natural and artificial materials. With an effective magnetic field for uncharged particles, many intriguing phenomena are observed in several systems like photonic Floquet topological insulator. However, previous researches about the gauge field mostly focus on limited dimensions such as the Dirac spinor in graphene materials. Here, an orbital gauge field based on photonic triangular lattices is first proposed and experimentally observed. Disclination defects with Frank angle Ω created on such lattices breaks the original lattice symmetry and generates purely geometric gauge field operating on orbital basis functions. Interestingly, it is found that bound states near zero energy with the orbital angular momentum (OAM) l = 2 are intensively confined at the disclination as gradually expanding Ω. Moreover, the introduction of a vector potential field breaks the time-reversal symmetry of the orbital gauge field, experimentally manifested by the chiral transmission of light on helical waveguides. The orbital gauge field further suggests fantastic applications of manipulating the vortex light in photonic integrated devices.

Design, synthesis and biological evaluation of novel 9-methyl-9H-purine and thieno[3, 2-d]pyrimidine derivatives as potent mTOR inhibitors.

The mammalian target of rapamycin (mTOR) has been proved to be an effective target for cancer therapy. Two kinds of mTOR inhibitors, the rapalogs and mTOR kinase inhibitors (TORKi), have been developed and clinically validated in several types of malignancies. Compared with rapalogs, TORKi can exert better antitumor activity by inhibiting both mTORC1 and mTORC2, but the clinical development of current TORKi candidates has been relative slow, more TORKi with novel scaffold need to be developed to expand the current pipelines. In this study, a series of 9-methyl-9H-purine and thieno[3, 2-d]pyrimidine derivatives were designed, synthesized and biological evaluation. Most of these compounds exhibited good mTOR kinase inhibitory activity and selectivity over PI3Kα. Subsequent antiproliferative assay allowed us to identify the lead compound 15i, which display nanomolar to low micromolar IC50s against six human cancer cell lines. 15i could induce cell cycle arrest of MCF-7, PC-3 and A549 cells at the G0/G1 phase and suppress the migration and invasion of these cancer cells by suppressing the phosphorylation of AKT and P70S6 kinase. It could also regulate autophagy-related proteins to induce autophagy. Therefore, 15i would be a starting point for the development of new TORKi as anticancer drug.

Inhibition and Reconstruction of Zener Tunneling in Photonic Honeycomb Lattices.

Quantum coherence is the central element of particle states, and it characterizes the overall performance of various quantum materials. Bloch oscillation is a fundamental coherent behavior of particles under a static potential, which can be easily destroyed by Zener tunneling in multiband 2D lattice materials. The control of Zener tunneling therefore plays the key role in quantum engineering for complicated physical systems. Here, the inhibition and reconstruction of Zener tunneling in photonic honeycomb lattices are experimentally demonstrated.  Deformed honeycomb lattices are integrated and an effective static potential is realized on the 2D lattice materials. Zener tunneling disappears in stretch-type lattices and wave packets stay in the dispersionless upper energy band. On the contrary, Zener tunneling is greatly enhanced in compression-type lattices and wave packets exhibit directional oscillations without branches, which manifest the preserved coherence of the wave packets. The results demonstrate the protection of photonic coherence by structurally controlling the Zener tunneling, representing a step toward flexible quantum engineering for large-scale artificial quantum materials.

Identification of a selective BRD4 PROTAC with potent antiproliferative effects in AR-positive prostate cancer based on a dual BET/PLK1 inhibitor.

BRD4-targeted proteolysis targeting chimera (PROTAC) have exhibited promising in vitro and in vivo anticancer activity in a number of cancer models. However, the clinical development of current reported BRD4-PROTACs have stagnated, largely due to the safety risks caused by their poor degradation selectivity. In this study, we designed and synthesized a series of PROTACs based on our recently reported dual BET/PLK1 inhibitor WNY0824, which led to the discovery of an isoform-selective and potent BRD4-PROTAC 12a (WWL0245). WWL0245 exhibited excellent selective cytotoxicity in the BETi sensitive cancer cell lines, including AR-positive prostate cancer cell lines. It could also efficiently induce ubiquitin-proteasomal degradation of BRD4 in AR-positive prostate cancer cell lines, with sub-nanomolar half-maximal degrading concentration (DC50) and maximum degradation (Dmax) > 99%. Moreover, WWL0245 induced cell cycle arrest at the G0/G1 phase and apoptosis in AR-positive prostate cancer by downregulation of the protein levels of AR, PSA and c-Myc as well as transcriptionally suppressed AR-regulated genes. WWL0245 was thus expected to be developed as a promising drug candidate for AR-positive prostate cancer and a valuable tool compound to study the biological function of BRD4.