Design of High-Performance Inorganic–Organic Hybrid Nonlinear Optical Materials Using Superhalogen Al₁₃ and Dianhydrides

Novel inorganic–organic hybrid complexes Al13–X (X represents the dianhydrides PMDA, NTCDA, and PTCDA) are theoretically designed and studied using density functional theory (DFT) and time-dependent DFT. These conjugated dianhydrides containing four acceptor carbonyl groups are commonly used as electron acceptor materials. These compounds possess large binding energies, reflecting the sufficient binding of Al13 to the dianhydride molecule. The binding nature of the complexes is of charge transfer type, i.e., electrons are transferred from the aluminum cluster to the dianhydride. All of the aimed complexes have large mean polarizability (α0) and first hyperpolarizability (β0). The β0 values are explained on the basis of electronic transitions in crucial excited states using the TD-DFT method. Additionally, the hole–electron distribution was analyzed, revealing the nature of electronic excitation. Absorption spectra analysis shows that these complexes have an excellent infrared (IR) transparent region (1000–5000 nm). Therefore, these inorganic–organic hybrid complexes with high stability can be considered as potential candidates for new IR nonlinear optical molecules

Characterization of interactions of simvastatin, pravastatin, fluvastatin, and pitavastatin with bovine serum albumin: multiple spectroscopic and molecular docking

<p>The binding interactions of simvastatin (SIM), pravastatin (PRA), fluvastatin (FLU), and pitavastatin (PIT) with bovine serum albumin (BSA) were investigated for determining the affinity of four statins with BSA through multiple spectroscopic and molecular docking methods. The experimental results showed that SIM, PRA, FLU, and PIT statins quenched the intrinsic fluorescence of BSA through a static quenching process and the stable stains–BSA complexes with the binding constants in the order of 10⁴ M⁻¹ at 298 K were formed through intermolecular nonbond interaction. The values of Δ<i>H</i>⁰, Δ<i>S</i>⁰ and Δ<i>G</i>⁰ in the binding process of SIM, PRA, FLU, and PIT with BSA were negative at the studied temperature range, suggesting that the binding process of four statins and BSA was spontaneous and the main interaction forces were van der Waals force and hydrogen-bonding interactions. Moreover, the binding of four statins with BSA was enthalpy-driven process due to |Δ<i>H</i>°|>|<i>T</i>Δ<i>S</i>°| under the studied temperature range. From the results of site marker competitive experiments and molecular docking, subdomain IIIA (site II) was the primary binding site for SIM, PRA, FLU, and PIT on BSA. The results of UV–vis absorption, synchronous fluorescence, 3D fluorescence and FT-IR spectra proved that the slight change in the conformation of BSA, while the significant changes in the conformation of SIM, PRA, FLU, and PIT drug in statin–BSA complexes, indicating that the flexibility of statin molecules plays an important role in increasing the stability of statin–BSA complexes.</p

Cell line copy number and protein expression.

<p>(a) Compared to the RBE cell line, copy numbers in the SNU1079 cell line was decreased. Data represent means ± standard deviations for three independent experiments. (b) The result was correlated with the protein expression demonstrated by Western blot analysis.</p

Silencing of <i>IRS2</i>, <i>CUL4A</i> and <i>TFDP1</i> in iCCA cells.

<p>(a) RBE cells were transiently transfected with siRNAs (RBE-siIRS2, RBE-siCUL4A and RBE-siTFDP1). The effect of gene expression after manipulation on growth potential was determined by Western blotting using anti-PCNA antibody (left) and manual counting of total cell numbers (right). (b) Silencing of the target genes, which were confirmed by Western blotting, dramatically reduced the mobility potential of RBE cells. Data represent means ± standard deviations for three independent experiments.</p

Cell line mobility potential.

<p>The RBE cell line demonstrated an increased number of migratory and invasive cells on the bottom of the wells. In contrast, the SNU1079 cell line containing a deletion of target genes displayed a significant decrease to mobility potential. Data represent means ± standard deviations for three independent experiments.</p

Kaplan-Meier survival curves for patients categorized by gene copy numbers.

<p>Statistical significance was observed among groups. (CN < 2: copy numbers less than two for all three markers of the 3-marker combination; 2 < CN < 4: copy numbers between two and four for at least one of three markers; 4 < CN: copy numbers more than four for all three markers)</p

Immunohistochemical analysis in tumors (T) of intrahepatic cholangiocarcinoma and normal bile ductules (N) of the adjacent portal tracts.

<p>Positive nuclear staining was observed for CUL 4A and TFDP1, and cytoplasmic staining for IRS2 in tumor cells with amplification of target genes (a, e, i), compared with normal bile ductules in the adjacent portal tracts (b, f, j). Loss of expression for CUL 4A, IRS2, and TFDP1 (c, g, k) was observed in tumor cells containing a deletion of target genes, in contrast to their normal counterparts (d, h, l). Original magnification: × 200.</p

Two pairs of unusual melibiose and raffinose esters from <i>Scrophularia ningpoensis</i>

<p>A pair of unusual melibiose esters (<b>1<i>α</i></b>/<b>1<i>β</i></b>) and a pair of unusual raffinose esters (<b>2<i>α</i>/2<i>β</i></b>), were isolated from <i>Scrophularia ningpoensis</i>. Structures of them were established by detailed spectroscopic analyses to be 6-<i>O</i>-(<i>E</i>)-cinnamoyl-<i>α</i>-d-galactopyranosyl-(1→6)-<i>α</i>(<i>β</i>)-d-glucopyranose (<b>1<i>α</i></b>/<b>1<i>β</i></b>) and 6-<i>O</i>-(<i>E</i>)/(<i>Z</i>)-cinnamoyl-<i>α</i>-d-galactopyranosyl-(1→6)-<i>α</i>-d-glucopyranosyl-(1→2)-<i>β</i>-d-fructofuranose (<b>2<i>α</i>/2<i>β</i></b>), respectively. All these compounds were evaluated for antifouling activity against the settlement of <i>Balanus amphitrite</i> larvae, along with the cytotoxic effect against the proliferation of HeLa cell lines.</p

A new sesquiterpene from the gorgonian coral <i>Menella</i> sp.

<p>A new sesquiterpene named menecubebane B (1) and a known analogue (2) were isolated from the gorgonian coral <i>Menella</i> sp. Their structures were elucidated by the extensive analyses of spectroscopic data and by the comparison with related literature. Cytotoxic effect against both Eca9706 and HeLa cell lines was evaluated, revealing 1 exhibited moderate cytotoxicity against the two cell lines involved with IC₅₀ values being 20.8 and 30.6 μM, respectively.</p

Table1_Hydroxychloroquine attenuates autoimmune hepatitis by suppressing the interaction of GRK2 with PI3K in T lymphocytes.DOCX

Hydroxychloroquine (HCQ) is derivative of the heterocyclic aromatic compound quinoline, which has been used for the treatment of autoimmune diseases. The central purpose of this study was to investigate therapeutic effects and inflammatory immunological molecular mechanism of HCQ in experimental autoimmune hepatitis (AIH). Treatment with HCQ ameliorated hepatic pathologic damage, inflammatory infiltration, while promoted regulatory T cell (Treg) and down-regulated CD8+T cell differentiation in AIH mice induced by S-100 antigen. In vitro, HCQ also suppressed pro-inflammatory cytokine (IFN-γ, TNF-α, and IL-12) secretion, promoted anti-inflammatory cytokine (TGF-β1) secretion. HCQ mainly impaired T cell lipid metabolism but not glycolysis to promote Treg differentiation and function. Mechanistically, HCQ down-regulated GRK2 membrane translocation in T cells, inhibited GRK2-PI3K interaction to reduce the PI3K recruiting to the membrane, followed by suppressing the phosphorylation of PI3K-AKT-mTOR signal. Pretreating T cells with paroxetine, a GRK2 inhibitor, disturbed HCQ effect to T cells. HCQ also reversed the activation of the PI3K-AKT axis by 740 Y-P (PI3K agonist). Meanwhile, HCQ inhibited the PI3K-AKT-mTOR, JAK2-STAT3-SOCS3 and increased the AMPK signals in the liver and T cells of AIH mice. In conclusion, HCQ exhibited specific and potent therapeutic effects on AIH and attendant liver injury, which was attributed to HCQ acted on GRK2 translocation, inhibited metabolism-related PI3K-AKT and inflammation-related JAK2-STAT3 signal in T lymphocytes, thereby modulating lipid metabolism of T cell function to regulate Treg differentiation and function.</p