Studies of Coumarin Derivatives for Constitutive Androstane Receptor (CAR) Activation

Constitutive androstane receptor (CAR) activation has found to ameliorate diabetes in animal models. However, no CAR agonists are available clinically. Therefore, a safe and effective CAR activator would be an alternative option. In this study, sixty courmarin derivatives either synthesized or purified from Artemisia capillaris were screened for CAR activation activity. Chemical modifications were on position 5,6,7,8 with mono-, di-, tri-, or tetra-substitutions. Among all the compounds subjected for in vitro CAR activation screening, 6,7-diprenoxycoumarin was the most effective and was selected for further preclinical studies. Chemical modification on the 6 position and unsaturated chains were generally beneficial. Electron-withdrawn groups as well as long unsaturated chains were hazardous to the activity. Mechanism of action studies showed that CAR activation of 6,7-diprenoxycoumarin might be through the inhibition of EGFR signaling and upregulating PP2Ac methylation. To sum up, modification mimicking natural occurring coumarins shed light on CAR studies and the established screening system provides a rapid method for the discovery and development of CAR activators. In addition, one CAR activator, scoparone, did showed anti-diabetes effect in db/db mice without elevation of insulin levels.     

Molecular Engineering of Push–Pull Porphyrin Dyes for Highly Efficient Dye‐Sensitized Solar Cells: The Role of Benzene Spacers

Porphyrins have drawn much attention as sensitizers owing to the large absorption coefficients of their Soret and Q bands in the visible region. In a donor and acceptor zinc porphyrin we applied a new strategy of introducing 2,1,3‐benzothiadiazole (BTD) as a π‐conjugated linker between the anchoring group and the porphyrin chromophore to broaden the absorption spectra to fill the valley between the Soret and Q bands. With this novel approach, we observed 12.75 % power‐conversion efficiency under simulated one‐sun illumination (AM1.5G, 100 mW cm^?2). In this study, we showed the importance of introducing the phenyl group as a spacer between the BTD and the zinc porphyrin in achieving high power‐conversion efficiencies. Time‐resolved fluorescence, transient‐photocurrent‐decay, and transient‐photovoltage‐decay measurements were employed to determine the electron‐injection dynamics and the lifetime of the photogenerated charge carriers.     

Redox Chemistry of a Hydroxyphenyl‐Substituted Borane

Chemical reduction of a hydroxyphenyl‐substituted borane triggers a sequential electron‐ and intramolecular hydrogen‐atom‐transfer process to afford a hydridoborate phenoxide dianion. On the other hand, hydrogen‐atom abstraction of the borane leads to the isolation of a neutral borylated phenoxyl radical, which can be transformed to the corresponding benzoquinone borataalkene derivative by reduction with cobaltocene.     

AQP4 Attenuated TRAF6/NFκB Activation in Acrylamide-Induced Neurotoxicity

Acrylamide (ACR) is present in high-temperature-processed high-carbohydrate foods, cigarette smoke, and industrial pollution. Chronic exposure to ACR may induce neurotoxicity from reactive oxygen species (ROS); however, the mechanisms underlying ACR-induced neurotoxicity remain unclear. We studied 28-day subacute ACR toxicity by repeatedly feeding ACR (0, 15, or 30 mg/kg) to rats. We conducted RNA sequencing and Western blot analyses to identify differences in mRNA expression in the blood and in protein expression in the brain tissues, respectively, of the rats. AQP4 transient transfection was performed to identify potential associations with protein regulation. The rats treated with 30 mg/kg ACR exhibited hind-limb muscle weakness. Matrix metalloproteinase (MMP9) expression was higher in the ACR-treated group than in the control group. ACR induced MMP-9 and AQP4 protein expression in the brain tissues of the rats, which subsequently presented with neurotoxicity. In the in vitro study, Neuro-2a cells were transiently transfected with AQP4, which inhibited MMP-9 and TNF receptor-associated factor 6 (TRAF6) expression, and inhibited ACR induced expression of TRAF6, IκBα, and nuclear factor κB (NFκB). Using a combination of in vivo and in vitro experiments, this study revealed that depressive symptoms associated with ACR-induced neurotoxicity are associated with downregulation of AQP4 and induction of the TRAF6 pathway.     

Combining Complex and Radial Slave Boson Fields within the Kotliar–Ruckenstein Representation of Correlated Impurities

The gauge symmetry group of any slave boson representation allows to gauge away the phase of bosonic fields. One benefit of this radial field formulation is the elimination of spurious Bose condensations when saddle-point approximation is performed. Within the Kotliar–Ruckenstein representation, three of the four bosonic fields can be radial while the last one has to remain complex. In this work, the procedure to carry out the functional integration involving constrained fermionic fields, complex bosonic fields, and radial bosonic fields is presented. The correctness of the representation is verified by exactly evaluating the partition function and the Green's function of the Hubbard model in the atomic limit.     

Upper and Lower Bounds of Table Sums

For a group G,we produce upper and lower bounds for the sum of the entries of the Brauer character table of G and the projective indecomposable character table of G.When G is a π-separable group,we show that the sum of the entries in the table of Isaacs' partial characters is a real number,and we obtain upper and lower bounds for this sum.     

Handcuffed designs

Handcuffed designs are a particular case of block designs on graphs. A handcuffed design with parametersv, k, λ consists of a system of orderedk-subsets of av-set, called handcuffed blocks. In a block {A ₁,A ₂,?, A _k } each element is assumed to be handcuffed to its neighbours and the block containsk ? 1 handcuffed pairs (A ₁,A ₂), (A ₂,A ₃), ? (A _k?1,A _k ). These pairs are considered unordered. The collection of handcuffed blocks constitute a hundcuffed design if the following are satisfied: (1) each element of thev-set appears amongst the blocks the same number of times (and at most once in a block) and (2) each pair of distinct elements of thev-set are handcuffed in exactly λ of the blocks. If the total number of blocks isb and each element appears inr blocks the following conditions are necessary for the handcuffed design to exist:

1. λv(v?1) = (k?1) b,
2. rv = kb.

We denote byH(v, k, λ) the class of all handcuffed designs with parametersv, k, λ and sayH (v, k, λ) exists if there is a design with parametersv, k, λ. In this paper we prove that the necessary conditions forH (v, k, λ) exist are also sufficient in the following cases: (a)λ = 1 or 2; (b)k = 3; (c)k is evenk = 2h, and (λ, 2h ? 1) = 1; (d)k is odd,k = 2h + 1, and (λ, 4h)=2 or (λ, 4h)=1.