3-{[Bis(pyridin-2-ylmeth­yl)amino]­meth­yl}-2-hy­droxy-5-methyl­benz­aldehyde

In the title compound, C21H21N3O2, the pyridine rings and the benzene ring lie in a propeller arrangement around the central tertiary amine N atom. The dihedral angles formed by the benzene ring with the pyridine rings are 61.0 (3) and 49.6 (3)°, while the dihedral angle between the pyridine rings is 69.7 (3)°. The mol­ecular conformation is stabilized by intramolecular bifurcated O—H⋯N hydrogen bonds. In the crystal, inversion dimers are formed via pairs of C—H⋯N hydrogen bonds

A hybrid control method to suppress the three time fundamental frequency neutral-point voltage fluctuation in a VIENNA rectifier

This paper presents a solution to the control of the three times fundamental frequency fluctuation of the neutral-point in a VIENNA rectifier. A hybrid method combining a dynamic adjustment factor with a voltage deviation control of the split DC-link is proposed. The fluctuation of the neutral-point has been analyzed and the reason for the three times fundamental frequency fluctuation has been described using a mathematic model. As well as minimizing the three times fundamental frequency component in the neutral-point voltage the proposed control method also provides immunity to the influence of changes in the capacitor voltage. Furthermore, significant fluctuation in the neutral-point voltage caused by asymmetric capacitor parameters or unbalanced load can be effectively reduced by using a hybrid control method combining additional adjustment coefficients. The feasibility and effectiveness of the proposed strategy has been verified through the presented simulation and experimental results

Decreased NPC1L1 expression in the liver from Chinese female gallstone patients

<p>Abstract</p> <p>Background</p> <p>Cholesterol gallstone disease is a very common disease in both industrialized and developing countries. Many studies have found that cholesterol gallstones are more common in women than men. The molecular mechanisms underlying the relationship between female gallstone disease and hepatic sterol transporters are still undergoing definition and have not been evaluated in humans.</p> <p>Aims</p> <p>The aim of this study is to probe for underlying hepatic molecular defects associated with development of gallstones in female.</p> <p>Methods/Results</p> <p>Fifty-seven nonobese, normolipidemic Chinese female gallstone patients (GS) were investigated with 12 age- and body mass index-matched female gallstone-free controls (GSF). The bile from the female GS had higher cholesterol saturation than that from the female GSF. The hepatic NPC1L1 mRNA levels were lower in female GS, correlated with SREBP2 mRNA. NPC1L1 downregulation was confirmed at protein levels. Consistently, immunohistochemistry showed decreased NPC1L1 expression in female GS.</p> <p>Conclusions</p> <p>The decreased hepatic NPC1L1 levels in female GS might indicate a downregulated reabsorption of biliary cholesterol in the liver, which, in turn, leads to the cholesterol supersaturation of bile. Our data are consistent with the possibility that hepatic NPC1L1 may be mediated by SREBP2.</p

Testing and Data Reduction of the Chinese Small Telescope Array (CSTAR) for Dome A, Antarctica

The Chinese Small Telescope ARray (hereinafter CSTAR) is the first Chinese astronomical instrument on the Antarctic ice cap. The low temperature and low pressure testing of the data acquisition system was carried out in a laboratory refrigerator and on the 4500m Pamirs high plateau, respectively. The results from the final four nights of test observations demonstrated that CSTAR was ready for operation at Dome A, Antarctica. In this paper we present a description of CSTAR and the performance derived from the test observations.Comment: Accepted Research in Astronomy and Astrophysics (RAA) 1 Latex file and 20 figure

High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthritis (PRINT): A multicenter randomized clinical trial

Objectives: To determine whether prolonged intensive disease-modifying antirheumatic drug (DMARD) treatment (PRINT) leads to high remission and low relapse rates in patients with severe rheumatoid arthritis (RA). Methods: In this multicenter, randomized and parallel treatment trial, 346 patients with active RA (disease activity score (28 joints) [DAS28] (erythrocyte sedimentation rate [ESR]) &gt; 5.1) were enrolled from 9 centers. In phase 1, patients received intensive treatment with methotrexate, leflunomide, and hydroxychloroquine, up to 36 weeks, until remission (DAS28 ≤ 2.6) or a low disease activity (2.6 &#60; DAS28 ≤ 3.2) was achieved. In phase 2, patients achieving remission or low disease activity were followed up with randomization to 1 of 2 step-down protocols: leflunomide plus hydroxychloroquine combination or leflunomide monotherapy. The primary endpoints were good European League Against Rheumatism (EULAR) response (DAS28 (ESR) &#60; 3.2 and a decrease of DAS28 by at least 1.2) during the intensive treatment and the disease state retention rate during step-down maintenance treatment. Predictors of a good EULAR response in the intensive treatment period and disease flare in the maintenance period were sought. Results: A good EULAR response was achieved in 18.7%, 36.9%, and 54.1% of patients at 12, 24, and 36 weeks, respectively. By 36 weeks, 75.4% of patients achieved good and moderate EULAR responses. Compared with those achieving low disease activity and a high health assessment questionnaire (HAQ &gt; 0.5), patients achieving remission (DAS28 ≤ 2.6) and low HAQ (≤ 0.5) had a significantly higher retention rate when tapering the DMARDs treatment (P = 0.046 and P = 0.01, respectively). There was no advantage on tapering to combination rather than monotherapy. Conclusions: Remission was achieved in a proportion of patients with RA receiving prolonged intensive DMARD therapy. Low disease activity at the start of disease taper leads to less subsequent flares. Leflunomide is a good maintenance treatment as single treatment

Co-administration of Shexiang Baoxin Pill and Chemotherapy Drugs Potentiated Cancer Therapy by Vascular-Promoting Strategy

Effective delivery of chemotherapeutic agents to tumors is a critical objective of improved cancer therapy. Traditional antiangiogenic therapy aims at eradicating tumor blood vessels, but the subsequently reduced blood perfusion may limit the drug amount delivered into the tumor and potentially lead to tumor hypoxia, which has been proved to be unable to meet the therapeutic expectations. “Shexiang Baoxin Pill” (SBP) is a well-known traditional Chinese medicine (TCM) used in clinical treatment of cardiovascular diseases, which has the pharmacological effect of pro-angiogenesis demonstrated recently. In this study, we disclosed our finding that SBP could enhance the effective treatment performance of gemcitabine (GEM) while minimizing the toxic side effects caused by GEM. Mechanistically, SBP increased tumor angiogenesis, blood perfusion, vascular permeability, and vessel dilation, which subsequently favored the delivery of GEM to the tumor lesion. Moreover, combined treatment with SBP and GEM could modify tumor microenvironment and consequently overcome multidrug resistance, and this combination therapy is also suitable for combination of SBP with some other chemotherapeutic drugs as well. These results suggest that combining SBP with chemotherapeutic agents achieves better treatment efficiency, which can open an avenue for expanding the combined treatment of anti-cancer chemotherapeutic drugs with TCM

TMRT observations of 26 pulsars at 8.6 GHz

Integrated pulse profiles at 8.6~GHz obtained with the Shanghai Tian Ma Radio Telescope (TMRT) are presented for a sample of 26 pulsars. Mean flux densities and pulse width parameters of these pulsars are estimated. For eleven pulsars these are the first high-frequency observations and for a further four, our observations have a better signal-to-noise ratio than previous observations. For one (PSR J0742-2822) the 8.6~GHz profiles differs from previously observed profiles. A comparison of 19 profiles with those at other frequencies shows that in nine cases the separation between the outmost leading and trailing components decreases with frequency, roughly in agreement with radius-to-frequency mapping, whereas in the other ten the separation is nearly constant. Different spectral indices of profile components lead to the variation of integrated pulse profile shapes with frequency. In seven pulsars with multi-component profiles, the spectral indices of the central components are steeper than those of the outer components. For the 12 pulsars with multi-component profiles in the high-frequency sample, we estimate the core width using gaussian fitting and discuss the width-period relationship.Comment: 33 pages, 49 figures, 5 Tables; accepted by Ap

Autophagy and its therapeutic potential in diabetic nephropathy

Diabetic nephropathy (DN), the leading cause of end-stage renal disease, is the most significant microvascular complication of diabetes and poses a severe public health concern due to a lack of effective clinical treatments. Autophagy is a lysosomal process that degrades damaged proteins and organelles to preserve cellular homeostasis. Emerging studies have shown that disorder in autophagy results in the accumulation of damaged proteins and organelles in diabetic renal cells and promotes the development of DN. Autophagy is regulated by nutrient-sensing pathways including AMPK, mTOR, and Sirt1, and several intracellular stress signaling pathways such as oxidative stress and endoplasmic reticulum stress. An abnormal nutritional status and excess cellular stresses caused by diabetes-related metabolic disorders disturb the autophagic flux, leading to cellular dysfunction and DN. Here, we summarized the role of autophagy in DN focusing on signaling pathways to modulate autophagy and therapeutic interferences of autophagy in DN