Hydrogen Transfer Coupling with 100% Atom Economy: Synthesis of 2-Indolyltetrahydronaphthyridine Derivatives.

An iridium-catalyzed hydrogen transfer strategy, enabling straightforward access to tetrahydropyridine derivatives from aryl-1,8-naphthyridines and indolines was developed. This method has unprecedented advantages, including high step economy. In addition, it does not produce any byproducts or require an external high-pressure H2 gas source. The method offers an important platform for the transformation of 1,8-naphthyridines and indolines into functionalized products.

Pleiotropic Effects of Simvastatin on the Regulation of Potassium Channels in Monocytes.

PURPOSE: The underlying mechanism of pleiotropic effects of statins on atherosclerosis is still unclear. Kv1.3 and KCa3.1 are two potassium channels that might be involved in monocyte migration and atherosclerosis formation. The aim of this study was to investigate the effect of simvastatin on the Kv1.3 and KCa3.1 in monocyte. METHODS AND RESULTS: In human monocytic THP-1 cells, simvastatin significantly inhibited Kv1.3 mRNA and protein expression by real-time quantitative PCR analysis and western blotting. However, simvastatin had no effects on KCa3.1 mRNA and protein expression. By whole-cell patch clamp, simvastatin (10 µM) remarkably inhibited the current intensity of Kv1.3, but had no effect on KCa3.1. Simvastatin (10 µM) treatment significantly reduced the monocyte chemoattractant protein 1 (MCP-1)-induced monocyte migration. This inhibition was only partially reversed by mevalonate (1mM). In human peripheral blood mononuclear cells (PBMCs), both Kv1.3 and KCa3.1 mRNA expression were increased in patients with coronary artery diseases (CAD) (n = 20) compared to healthy controls (n = 22). However, simvastatin (40 mg per day) significantly inhibited the Kv1.3 but not KCa3.1 mRNA expression after 1 month and 3 months therapy in CAD patients. CONCLUSION: Our data suggested Kv1.3 in monocytes was a potential molecular target of the pleiotropic effects of statins. KCa3.1 might be another marker of CAD, but not associated with statins treatment.

Tuning of the stability and energy levels of singlet exciton fission relevant excited states of pentacenes by site-specific substitution.

Pentacene crystals or oligomers undergo efficient singlet exciton fission (SF) after photo-excitation, which is expected to be useful in overcoming the Shockley-Queisser theoretical limit of solar cells. However, pentacenes are extremely unstable in air due to oxidation by oxygen. In this work, we designed a group of pentacene compounds with different substituents at different positions. The energy levels of HOMO and LUMO, which are believed to be closely related to the stability of pentacene, were calculated. The relationship between the molecular structure and the stability was discussed. The driving force for SF was estimated from the difference between the energy of first singlet excited state (E(S1)) and the energy of two triplet excited state (2×E(T1)) following equation E(S1)-2E(T1). Strong electron-withdrawing groups can stabilize pentacene compounds significantly, but induce a decrease on the driving force of SF slightly. Electron-donating groups destabilize the pentacene compounds dramatically and hence the introduction of electron donating groups to pentacene is not recommended. TIPS is an ideal group to improve the stability of pentacene compounds. TIPS does not change the driving force of SF significantly. Sulfur containing groups are also efficient on stabilizing pentacene compounds. These groups increase the driving force of SF at ɑ position, and recued the driving force of SF at other positions. The results of this work provide a theoretical ground for rational design of new SF molecules based on pentacenes.

A modified fuzzy C-means method for segmenting MR images using non-local information.

BACKGROUND: In recent years, MR images have been increasingly used in therapeutic applications such as image-guided radiotherapy (IGRT). However, images with low contrast values and noises present challenges for image segmentation. OBJECTIVE: The objective of this study is to develop a robust method based on fuzzy C-means (FCM) method which can segment MR images polluted with Gaussian noise. METHODS: A modified FCM algorithm accommodating non-local pixel information via Hausdorff distance was developed for segmenting MR images. The membership and objective functions were modified accordingly. Segmentations with different weights of the Hausdorff distance were compared. RESULTS: Segmentation tests using synthetic and MR images showed that the proposed algorithm was better at resolving boundaries and more robust to Gaussian noise. By segmenting a sample MR image of a tumor, we further showed the capability of the method in capturing the centroid of the target region. CONCLUSIONS: The modified FCM algorithm with neighboring information can be used to segment blurry images with potential applications in segmenting motion MR images in image-guided radiotherapy (IGRT).

Sensitivity of KATP channels to cellular metabolic disorders and the underlying structural basis.

AIM: ATP-sensitive potassium (KATP) channels formed by a combination of SUR/Kir6.x subunits play a crucial role in protection against hypoxic or ischemic injuries resulting from cell metabolic disorders. In this study we investigated the effects of Na-azide, a metabolic inhibitor, on KATP channels expressed in Xenopus oocytes, and explored the structure basis for their sensitivity to cell metabolic disorders. METHODS: Six subtypes of KATP channels (wild SUR1/Kir6.2, SUR2B/Kir6.2, SUR1/Kir6.1, SUR2B/Kir6.1, SUR2A/Kir6.2 and SUR2A/Kir6.1), as well as eleven subtypes of KATP channels with mutant subunits were expressed in Xenopus oocytes. KATP currents were recorded using a two-electrode voltage clamp recording technique. The drugs were applied through bath. RESULTS: Except SUR2A/Kir6.1, five subtypes of KATP channels were activated by Na-azide (3 mmol/L) with an order of the responses: SUR1/Kir6.2>SUR2B/Kir6.2>SUR1/Kir6.1>SUR2B/Kir6.1>SUR2A/Kir6.2, and the opening rate (t1/2) was SUR1/Kir6.x>SUR2B/Kir6.x>SUR2A/Kir6.2. Furthermore, Kir6.2, rather than Kir6.1, had intrinsic sensitivity to Na-azide, and the residues involved in ATP-binding (R50 and K185) or pH-sensing (H175) were associated with the sensitivity of the Kir6.2 subunit to Na-azide. Moreover, the residues (K707 and K1348) within the Walker A (WA) motifs of two nucleotide-binding domains (NBDs) were essential for SUR2B/Kir6.x (especially SUR2B/Kir6.1) channel activation by Na-azide, suggesting a key role for Mg-adenine nucleotide binding and/or hydrolysis in the SUR2B subunit. CONCLUSION: Among the six subtypes of KATP channels, SUR1/Kir6.2 is the most sensitive, whereas SUR2A/Kir6.1 is insensitive, to cell metabolic disorders. The Kir6.2 subunit, rather than the Kir6.1 subunit, has intrinsic sensitivity to cell metabolic disorders. The residues (K707 and K1348) within the WA motifs of SUR2B are important for the sensitivity of SUR2B/Kir6.x channels to cell metabolic disorders.

Synthesis of substituted 6-amino-4-(2,4-dimethoxyphenyl)-[1,2]dithiolo[4,3-b]pyrrol-5-ones and their raising leukocyte count activities.

The design and synthesis of a series of substituted 6-amino-4-(2,4-dimethoxyphenyl)-[1,2]dithiolo[4,3-b]pyrrol-5-ones are described. All the synthesized compounds were evaluated for raising leukocyte count activities in normal mice. Four compounds (8a, b, d, h) exhibited raising leukocyte count activities close or higher than positive control recombinant human granulocyte colony stimulating factor (rhG-CSF), and some (8e-g, k, p, r) had a moderate effect. Among them, the most potent compound 8a was evaluated for its antileukopenia activity in cyclophosphamide (CTX) treated mice. Interestingly, 8a exhibited significant antileukopenia activity as compared to rhG-CSF. The results suggest that this kind of compounds might be utilized for the development of new candidate for treatment of leukocytopenia.

[Effects of long-term external use of goupi gao on renal functions and lead accumulation in rats].

OBJECTIVE: To observe the effect of long-term external use of Goupi Gao on renal function and lead accumulation in rats. METHOD: Rats were externally administered with Goupi Gao at different doses (7, 3.5 and 1.75 g x kg(-1)) for 90 d. At 45 days and 90 days after administration, the renal indicator, levels of blood urea nitrogen (BU) and creatinine (Cr) in serum, beta2-microglobulin (beta2-MG) and N-acetyl-beta-D-glucosaminidase (NAG) in urine were determined. Lead content in kidneys was detected by atomic absorption spectrometry. RESULT: A 90-day administration with Goupi Gao significantly enhanced the renal indicator, levels of NAG in urine and lead content in renal, when compared with the normal rats. However, the levels of BUN and beta2-MG as well as renal pathology in Goupi Gao treated rats were not obviously changed. CONCLUSION: Consecutive administration of Goupi Gao for 90 days can increase the renal indicator and levels of NAG in urine, enhance the accumulation of lead in renal, but with no effect on excretory function of kidneys and organic changes.

[Effect of ZL-004 on raising leukocyte count].

This study is to investigate the effect of ZL-004 on normal mouse and mice with leukopenia induced by chemotherapeutic agents. 5-Fluorouracil were administered intraperitoneally to mice to develop leucopenia, and the mice were treated with ZL-004. The number of peripheral leukocytes and the percentage of granulocyte in total WBC were examined. The results are that ZL-004 markedly raise peripheral blood leukocytes in the normal mice and the mice model of leukopenia. So, ZL-004 could protect mice against 5-fluorouracil damage and raise peripheral blood leukocyte. Features of bone marrow smears is myeloproliferative hyperactivity in the mice, particularly the matured granulocytic series were observed. The mechanism of ZL-004 is to act on the mouse bone marrow causing proliferation and differentiation.