Targeting peroxisome proliferator-activated receptor γ proteasomal degradation by magnolol is a potential avenue for adipogenesis-mediated metabolic homeostasis.

OBJECTIVE: Adipogenesis has been recognized as an attractive avenue for maintaining systemic homeostasis, with peroxisome proliferator-activated receptor γ (PPARγ) showing predominant roles in this process. This study aims to identify promising drug candidates by targeting PPARγ for adipogenesis-based metabolic homeostasis and to clarify the detailed mechanisms. METHODS: Molecular events contributing to adipogenesis were screened, which identified PPARγ as having the predominant role. Promising agents of adipogenesis agonism were screened using a PPARγ-based luciferase reporter assay. The functional capacity and molecular mechanisms of magnolol were intensively examined using 3T3-L1 preadipocytes and dietary models. RESULTS: This study found that F-box only protein 9 (FBXO9)-mediated lysine 11 (K11)-linked ubiquitination and proteasomal degradation of PPARγ are critically required during adipogenesis and systemic homeostasis. Notably, magnolol was identified as a potent adipogenesis activator by stabilizing PPARγ. The pharmacological mechanisms investigations clarified that magnolol directly binds to PPARγ and markedly interrupts its interaction with FBXO9, leading to a decline in K11-linked ubiquitination and proteasomal degradation of PPARγ. Clinically important, magnolol treatment significantly facilitates adipogenesis in vitro and in vivo. CONCLUSIONS: The downregulation of K11-linked ubiquitination of PPARγ caused by FBOX9 is essentially required for adipogenesis, while targeting PPARγ-FBXO9 interaction provides a new avenue for the therapy of adipogenesis-related metabolic disorder.

Pancharatnam-Berry geometric phase memory based on spontaneous parametric down-conversion.

Phase memory is an effect in which the interaction between a coherent pump beam and a nonlinear crystal generates photon pairs via the spontaneous parametric down-conversion process, then the down-converted photons (signal and idler) can carry the phase information of the pump beam. There has been much research on the memory of the dynamic phase so far; however, there is no report on the memory of non-dynamic phase, to the best of our knowledge. Here we acquire a Pancharatnam-Berry (PB) geometric phase in a physical system when light travels along a trajectory in polarization-state space. Induced coherence occurs in a cascaded scheme composed of two nonlinear crystals, when the idler photons in both crystals are aligned to be indistinguishable. A NOON ($N\; = \;{2}$N=2) state is established when blocking the two idler photons. We explore the PB geometric phase memory of the NOON state and induced coherence. We find that the first-order interference of the two-photon state or signal photons can be controlled by introducing the PB geometric phase to the pump light. This may facilitate precise control of the phase of the down-converted photons.

Manipulation of eight-dimensional Bell-like states.

High-dimensional Bell-like states are necessary for increasing the channel capacity of the quantum protocol. However, their preparation and measurement are still huge challenges, especially for the latter. Here, we prepare an initial eight-dimensional Bell-like state based on hyperentanglement of spin and orbital angular momentum (OAM) of the first and the third orders. We design simple unitary operations to produce eight Bell-like states, which can be distinguished completely in theory among each other. We propose and illustrate a multiple projective measurement scheme composed of only linear optical elements and experimentally demonstrate that all the eight hyperentangled Bell-like states can be completely distinguished by our scheme. Our idea of manipulating the eight Bell-like states is beneficial to achieve the 3-bit channel capacity of quantum protocol, opening the door for extending applications of OAM states in future quantum information technology.

Compact, robust, and high-efficiency generator of vector optical fields.

We design and realize a generator that can convert an orbital angular momentum (OAM) state into a vector polarization state. The generator is integrated by several commonly used optical elements and easy to make or glued. Compared with traditional interferometric ways for generating the vector optical fields, this integrated generator has compact and robust advantages and especially a high-efficiency of 87%.

High-efficiency and flexible generation of vector vortex optical fields by a reflective phase-only spatial light modulator.

The scheme for generating vector optical fields should have not only high efficiency but also flexibility for satisfying the requirements of various applications. However, in general, high efficiency and flexibility are not compatible. Here we present and experimentally demonstrate a solution to directly, flexibly, and efficiently generate vector vortex optical fields (VVOFs) with a reflective phase-only liquid crystal spatial light modulator (LC-SLM) based on optical birefringence of liquid crystal molecules. To generate the VVOFs, this approach needs in principle only a half-wave plate, an LC-SLM, and a quarter-wave plate. This approach has some advantages, including a simple experimental setup, good flexibility, and high efficiency, making the approach very promising in some applications when higher power is need. This approach has a generation efficiency of 44.0%, which is much higher than the 1.1% of the common path interferometric approach.

Double Activation Catalysis for α'-Alkylidene Cyclic Enones with Chiral Amines and Thiols.

Cooperative catalysis has contributed greatly to the progress of asymmetric synthesis. However, double-activation catalysis has been less explored, especially for covalently tethered species. Here, we present a double-activation strategy for α'-alkylidene cyclic enone substrates that uses a chiral primary amine and 2-mercaptobenzoic acid to promote regio- and chemoselective addition to generate the complex interrupted iminium ion species. Significantly enhanced reactivity and enantioselectivity were observed for ß-regioselective Michael addition and Friedel-Crafts alkylation with malononitriles and indoles, respectively, which produced a spectrum of chiral cyclic adducts with an exo-alkylidene group. Moreover, a HRMS study detected a few key covalently tethered intermediates among the substrates and catalysts, which helped elucidate the catalytic mechanism.

Switchable regioselectivity in amine-catalysed asymmetric cycloadditions.

Building small-molecule libraries with structural and stereogenic diversity plays an important role in drug discovery. The development of switchable intermolecular cycloaddition reactions from identical substrates in different regioselective fashions would provide an attractive protocol. However, this also represents a challenge in organic chemistry, because it is difficult to control regioselectivity to afford the products exclusively and at the same time achieve high levels of stereoselectivity. Here, we report the diversified cycloadditions of α'-alkylidene-2-cyclopentenones catalysed by cinchona-derived primary amines. An asymmetric γ,ß'-regioselective intermolecular [6+2] cycloaddition reaction with 3-olefinic (7-aza)oxindoles is realized through the in situ generation of formal 4-aminofulvenes, while a different ß,γ-regioselective [2+2] cycloaddition reaction with maleimides to access fused cyclobutanes is disclosed. In contrast, an intriguing α,γ-regioselective [4+2] cycloaddition reaction is uncovered with the same set of substrates, by employing an unprecedented dual small-molecule catalysis of amines and thiols. All of the cycloaddition reactions exhibit excellent regio- and stereoselectivity, producing a broad spectrum of chiral architectures with high structural diversity and molecular complexity.

Cross-conjugated Trienamine Catalysis with α'-Alkylidene 2-Cyclohexenones: Application in ß,γ-Regioselective Aza-Diels-Alder Reaction.

Endo-type cross-conjugated trienamines between highly congested α'-alkylidene 2-cyclohexenones and a chiral primary amine catalyst serve as HOMO-raised dienophiles in inverse-electron-demand aza-Diels-Alder cycloadditions with a number of 1-azadiene substrates. The reactions exhibit exclusive ß,γ-regioselectivity, and multifunctional products with high molecular complexity are efficiently constructed in excellent diastereo- and enantioselectivity (>19:1 d.r., up to 99 % ee).