[Retracted] Upregulation of microRNA­181b inhibits CCL18­induced breast cancer cell metastasis and invasion via the NF­κB signaling pathway.

[This retracts the article DOI: 10.3892/ol.2016.5230.].

Magnetodielectric Effect in a Triangular Dysprosium Single-Molecule Toroics.

Single-molecule toroics are molecular magnets with vortex distribution of magnetic moments. The coupling between magnetic and electric properties such as the magnetodielectric effect will provide potential applications for them. Herein, the observation of significant magnetodielectric effect in a triangular Dy3 crystal with toroidal magnetic moment and multiple magnetic relaxations is reported. The analysis of magnetic and electric properties implies that the magnetodielectric effect is closely related to the strong spin-lattice coupling, magnetic interactions of Dy3+ ions, as well as molecular packing models.

Electrical detection and modulation of magnetism in a Dy-based ferroelectric single-molecule magnet.

Electrical control of magnetism in single-molecule magnets with peculiar quantum magnetic behaviours has promise for applications in molecular electronics and quantum computing. Nevertheless, such kind of magnetoelectric effects have not been achieved in such materials. Herein, we report the successful realization of significant magnetoelectric effects by introducing ferroelectricity into a dysprosium-based single-molecule magnet through spatial cooperation between flexible organic ligands and halide ions. The stair-shaped magnetization hysteresis loop, alternating current susceptibility, and magnetic relaxation can be directly modulated by applying a moderate electric field. Conversely, the electric polarization can be modulated by applying a small magnetic field. In addition, a resonant magnetodielectric effect is clearly observed, which enables detection of quantum tunnelling of magnetization by a simple electrical measurement. The integration of ferroelectricity into single-molecule magnets not only broadens the family of single-molecule magnets but also makes electrical detection and modulation of the quantum tunnelling of magnetization a reality.

Reversible single-crystal to single-crystal transformation between triangular single-molecule toroics.

We report a method for synthesizing single-molecule magnets through a single-crystal to single-crystal transformation. This process yields two single-molecule magnets with similar triangular Dy3 cores but distinct solvents and space groups achieved via solvent exchange. Magnetic properties reveal that both Dy3 molecules exhibit similar toroidal moments but manifest diverse multiple magnetization dynamic behaviors owing to the spin-lattice coupling influence from different solvent molecules.

Comparative transcriptomic analysis revealed changes in multiple signaling pathways involved in protein degradation in the digestive gland of Mytilus coruscus during high-temperatures.

As a result of global warming, the Mytilus coruscus living attached in the intertidal zone experience extreme and fluctuating changes in temperature, and extreme temperature changes are causing mass mortality of intertidal species. This study explores the transcriptional response of M. coruscus at different temperatures (18 °C, 26 °C, and 33 °C) and different times (0, 12, and 24 h) of action by analyzing the potential temperature of the intertidal zone. In response to high temperatures, several signaling pathways in M. coruscus, ribosome, endocytosis, endoplasmic reticulum stress, protein degradation, and lysosomes, interact to counter the adverse effects of high temperatures on protein homeostasis. Increased expression of key genes, including heat shock proteins (Hsp70, Hsp20, and Hsp110), Lysosome-associated membrane glycoprotein (LAMP), endoplasmic reticulum chaperone (BiP), and baculoviral IAP repeat-containing protein 7 (BIRC7), may further mitigate the effects of heat stress and delay mortality in M. coruscus. These results reveal changes in multiple signaling pathways involved in protein degradation during high-temperature stress, which will contribute to our overall understanding of the molecular mechanisms underlying the response of M. coruscus to high-temperature stress.

Design, Synthesis, and Fungicidal Evaluation of Novel N-Methoxy Pyrazole-4-Carboxamides as Potent Succinate Dehydrogenase Inhibitors.

Succinate dehydrogenase (SDH, EC 1.3.5.1, also known as complex II) has been recognized as one of the most promising targets of fungicides. Here, based on the binding mode of pydiflumetofen with SDH, the carbon-carbon double bond was introduced into the chemical of pydiflumetofen and then produced the target compounds 6a-6o. The enzymatic inhibitory activity and structure-activity relationship (SAR) study showed that the 2-position and 4-position in terminal benzene were positive to increasing activity. Furthermore, fungicidal activity results in greenhouses indicated that compound 6o showed good control effects against wheat powdery mildew (WPM), cucumber powdery mildew (CPM), and southern corn rust (SCR), showing its broad-spectrum property. Especially, compound 6o exhibited 95 and 75% control effects against CPM and SCR at 6.25 mg/L, respectively, which are better than pydiflumetofen (80% control effects against CPM and 15% against SCR), indicating its potency that is worthy of further development.

Ferroelectric Single-Molecule Magnet with Toroidal Magnetic Moments.

Materials that coexist magnetic and electric properties on the molecular scale in single-molecule magnets (SMMs) with peculiar quantum behaviors have promise in molecular electronics and spintronics. Nevertheless, such molecular materials are limited in potentials because their magnetic signal cannot be transformed into an electrical signal through magnetoresistance or Hall effects for their high insulativity. The discovery of an entirely new material, ferroelectric SMMs (FE SMMs) is reported. This FE SMM also shows single-molecule magnetic behaviors, toroidal magnetic moments, and room-temperature ferroelectricity. The toroidal moment is formed by a vortex distribution of magnetic dipoles in triangular Dy3 clusters. The analysis of ac magnetic susceptibility reveals the coexistence of three distinct magnetic relaxation processes at low temperatures. The ferroelectricity is introduced by incorporating polar alcohol molecules in the structure, which is confirmed by the X-ray diffraction and optical second harmonic generation (SHG) measurements. Moreover, the dielectric measurements reveal a ferroelectric-to-ferroelectric phase transition around 150 K due to the symmetry change from Pc to Pna21 . The coexistence of toroidal moment and ferroelectricity along with quantum magnetism in the rare-earth single-molecule magnets yields a unique class of multiferroics.

[Effect of Rheb1 in the Development of Mouse Megakaryocyte-Erythroid Progenitor Cells].

OBJECTIVE: To investigate the effect of Rheb1 in the development of mouse megakaryocyte-erythroid progenitor cells and its related mechanism. METHODS: Rheb1 was specifically knocked-out in the hematopoietic system of Vav1-Cre;Rheb1fl/fl mice(Rheb1Δ/Δ mice). Flow cytometry was used to detect the percentage of red blood cells in peripheral blood and erythroid cells in bone marrow in Vav1-Cre;Rheb1fl/fl mice and control mice. The CFC assay was used to detect the differentiation ability of Rheb1 KO megakaryocyte-erythroid progenitor cells and control cells. Real-time fluorescence quantification PCR was used to detect the relative expression of PU.1,GATA-1,GATA-2,CEBPα and CEBPß of Rheb1 KO megakaryocyte-erythroid progenitor cells and control cells. Rapamycin was added to the culture medium, and it was used to detect the changes in cloning ability of megakaryocyte-erythroid progenitor cells from wild-type mice in vitro. RESULTS: After Rheb1 was knocked out, the development and stress response ability of megakaryocyte-erythroid progenitor cells in mice were weaken and the differentiation ability of megakaryocyte-erythroid progenitor cells in vitro was weaken. Moreover, the expression of GATA-1 of megakaryocyte-erythroid progenitor cells was decreased. Further, rapamycin could inhibit the differentiative capacity of megakaryocyte-erythroid progenitor cells in vitro. CONCLUSION: Rheb1 can regulate the development of megakaryocyte-erythroid progenitor cells probably through the mTOR signaling pathway in mice.

Discovery of a Fungicide Candidate Targeting Succinate Dehydrogenase via Computational Substitution Optimization.

Succinate dehydrogenase (SDH, EC 1.3.5.1) has proven to be an important fungicidal target, and the inhibition of SDH is useful in the treatment of plant pathogens. The discovery of a novel active SDH inhibitor is of high value. Herein, we disclose the discovery of a potent, highly active inhibitor as a fungicide candidate by using a computational substitution optimization method, a fast drug design method developed in our laboratory. The greenhouse experiments showed that compound 17c exhibited high protective activity against south corn rust, soybean rust (SBR), and rice sheath blight at a very low dosage of 0.781 mg/L. Moreover, the field trials indicated that compound 17c is comparable to and even better than commercial fungicides against SBR and cucumber powdery mildew at 50 mg/L concentration. Most surprisingly, compound 17c resulted to be strictly better in curative activity than the commercial fungicide benzovindiflupyr. The computation results indicated that 17c could form another hydrogen bond with C_S42 and then lead to strong van der Waals and electronic interactions with SDH. Our results suggested that 17c is a potential fungicide candidate for SDH.

[Review of chemical constituents,pharmacological effects and clinical applications of Danggui Buxue Decoction and prediction and analysis of its Q-markers].

Danggui Buxue Decoction is a classic prescription of Qi and blood tonification, which is mainly applied in treating fatigue, internal damage Qi weakness, blood deficiency, and outward going of floating Yang. Modern pharmacology shows that it can promote hematopoiesis, regulate immunity, and protect heart and cerebral vessels. The prescription, often used for the treatment of anemia and other diseases in clinic, is composed of Astragali Radix and Angelicae Sinensis Radix at a dosage ratio of 5∶1. It is a modern compound prescription for invigorating Qi and generating blood. Based on the review of the chemical constituents, pharmacological effects, and clinical applications of Danggui Buxue Decoction, its Q-marker was predicted and analyzed according to the "five principles" of Chinese medicine Q-marker--quality transmissibility and traceability, ingredient specificity, component validity, component measurabi-lity, and formula compatibility environment. The results suggested that calycosin, calycosin-7-O-ß-D-glucoside, formononetin, ononin, astragaloside A, ferulic acid, and ligustilide could be used as Q-markers of Danggui Buxue Decoction, which provides reference for establishing the quality system of Danggui Buxue Decoction.

Enhancing the energy barrier and hysteresis temperature in two benchtop-stable Ho(iii) single-ion magnets.

The energy barrier and hysteresis temperature in two benchtop-stable D5h-symmetry HoIII single-ion magnets were significantly enhanced via the variation of the halogen anion. The coexistence of a high energy barrier of 418 K and hysteresis temperature of 15 K was observed in the bromide-ion containing HoIII single-ion magnet.

Systemic lupus erythematosus combined with primary hyperfibrinolysis and protein C and protein S deficiency: A case report.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by systemic involvement and multiple autoantibodies in the serum. Patients with protein C (PC) and protein S (PS) deficiency are prone to thrombosis. In contrast, patients with primary hyperfibrino-lysis tend to bleed. CASE SUMMARY: A 52-year-old female patient with bilateral pleural effusion was diagnosed with "tuberculous pleurisy" and treated with anti-tuberculosis drugs and prednisone. The coagulation-related laboratory results showed decreased fibrinogen, PC activity, PS activity, and antithrombin Ш activity. The immune-related laboratory results showed positive antinuclear antibody, anti-Smith antibody, anticardiolipin antibody (ACL), anti-ß2-glycoprotein I antibody (aß2GPI) and direct Coomb's test and decreased complement 3 and complement 4. Thoracoscopy was performed and bloody pleural fluid was drained. Pathology of the pleural biopsy showed lymphocytes, plasma cells, and a few eosinophils in adipose and fibrous connective tissue. Results of whole exome sequencing of blood showed no genetic mutations suggesting the presence of hereditary hematological diseases. The patient was finally diagnosed with SLE and primary hyperfibrinolysis, and was treated with prednisolone, hydroxychloroquine, and compound cyclophosphamide. CONCLUSION: PC and PS deficiency in SLE might be related to ACL and aß2GPI. SLE and primary hyperfibrinolysis can coexist in one patient, with both a risk of thrombosis and a risk of bleeding.

Highly enantioselective one-pot sequential synthesis of valerolactones and pyrazolones bearing all-carbon quaternary stereocentres.

Highly enantiopure and bioactive δ-valerolactones and pyrazolones, bearing α-all-carbon quaternary stereocentres, were successfully and sequentially prepared via a one-pot procedure starting from readily available, inexpensive materials, catalysed by a new chiral squaramide under mild reaction conditions. An organocatalytic Michael reaction afforded the valerolactones, while a one-pot Michael-hydrazinolysis-imidization cascade yielded the pyrazolones. This procedure is economically efficient and environmentally benign.

Discovery of Pyrazine-Carboxamide-Diphenyl-Ethers as Novel Succinate Dehydrogenase Inhibitors via Fragment Recombination.

The discovery of novel succinate dehydrogenase inhibitors (SDHIs) has attracted great attention worldwide. Herein, a fragment recombination strategy was proposed to design new SDHIs by understanding the ligand-receptor interaction mechanism of SDHIs. Three fragments, pyrazine from pyraziflumid, diphenyl-ether from flubeneteram, and a prolonged amide linker from pydiflumetofen and fluopyram, were identified and recombined to produce a pyrazine-carboxamide-diphenyl-ether scaffold as a new SDHI. After substituent optimization, compound 6y was successfully identified with good inhibitory activity against porcine SDH, which was about 2-fold more potent than pyraziflumid. Furthermore, compound 6y exhibited 95% and 80% inhibitory rates against soybean gray mold and wheat powdery mildew at a dosage of 100 mg/L in vivo assay, respectively. The results of the present work showed that the pyrazine-carboxamide-diphenyl-ether scaffold could be used as a new starting point for the discovery of new SDHIs.

[Review of chemical constituents, pharmacological effects and clinical applications of Suanzaoren Decoction and prediction and analysis of its Q-markers].

Suanzaoren Decoction is a classic prescription for nourishing the heart and liver, nourishing blood and tranquilizing the mind. It has the functions of sedation and hypnosis, anti-anxiety, anti-depression, anti-convulsion and so on. Modern clinic is mostly used to treat different types of insomnia, depression, neurasthenia, tension headache and vertigo. In this paper, the chemical consti-tuents, pharmacological effects and clinical application of Suanzaoren Decoction are reviewed. Based on this, the quality marker(Q-marker) of Suanzaoren Decoction was predicted and analyzed according to the "five principles" of Q-marker of traditional Chinese medicine--transmission and traceability, specificity, effectiveness, measurability and compatibility environment of compound prescriptions. The results indicated that jujuboside, spinosin, ferulic acid, senkyunolide Ⅰ, sarsasapogenin, mangiferin, liquiritoside and glycyrrhizic acid were predicted and analyzed, and those can be used as Q-markers of Suanzaoren Decoction. Subsequently, the above components can be selected as indicators to control and evaluate the quality of Suanzaoren Decoction and its preparations, and establish a quality traceability system.

Design and synthesis of potent inhibitors of bc1 complex based on natural product neopeltolide.

Neopeltolide, a natural product isolated from deep-water sponge specimen of the family neopeltidae, has been proven to be a novel inhibitor of cytochrome bc1. In this study, a series of neopeltolide derivatives was designed by replacing the 14-membered macrolactone with indole ring and confirmed by 1H NMR, 13C NMR, and HRMS. Based on the binding mode of 12h with bc1 complex, the IC50 values of compounds 16a-f (ranging from 0.70 to 1.46 µM) were improved significantly than the ester derivatives 12a-u by replacing the ester with amide linker. Subsequently, the molecular docking results indicated that compound 16e could form a π-π interaction with Phe274 and two H-bonds with Glu271 and His161 and the latter H-bond was found to account for its high activity. The present work accelerates the discovery of novel bc1 complex inhibitors to deal with the resistance that the existing bc1 complex inhibitors are facing and provides a valuable idea for the design of new fungicides.

Water Stable Heterometallic Zn-Tb Coordination Polymer for Rapid Detection of the Ultraviolet Filter Benzophenone.

Benzophenone (BP) is an ultraviolet filter (UVF) widely used in personal care products such as sunscreens and cosmetics. Excessive exposure to BP-type UVFs is a potential threat to human's health because of their endocrine-disrupting activity. Water stability of lanthanide compounds is crucial when they serve as luminescent sensors because of the practicality and recyclability. In this study, a water-stable luminescent Zn-Tb heterometallic coordination polymer was rationally designed and synthesized for rapid detection of BP. This material showed a high quenching effect, excellent selectivity, and fast response toward BP.

Evaluation of the Structure and Biological Activities of Condensed Tannins from Acanthus ilicifolius Linn and Their Effect on Fresh-Cut Fuji Apples.

Condensed tannins (CTS) have been isolated and purified from leaves of Acanthus ilicifolius Linn. And their structures were investigated by three methods: 13C nuclear magnetic resonance (13C NMR), reversed-phase high-performance liquid chromatography (RP-HPLC), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The results showed that the CTS were a mixture of catechin/epicatechin, galatechin/epicatechin, and amphicin/epigalin, and that the polymer chain lengths were 3-mers to 14-mers. Antityrosinase activities and antioxidant activities of the CTS from A. ilicifolius leaves were further studied. The IC50 of the CTS on mushroom tyrosinase activity was determined to be 19.7 ± 0.13 µg/mL, and inhibition type analyses indicated that the CTS were mixed type inhibitors and their inhibition CTS was reversible. The CTS from A. ilicifolius leaves also exhibited potential antioxidant activity. The IC50 of DPPH and ABTS scavenging activities were 104 ± 0.894 µg/mL and 86 ± 0.616 µg/mL, respectively. And the FRAP value was 758.28 ± 2.42 mg AAE/g. In addition, we found that the CTS from A. ilicifolius leaves had an excellent effect on preserving the quality of fresh-cut apples by preventing apples from browning through reducing polyphenol oxidase activities in apples.

Tuning the magnetization dynamics of TbIII-based single-chain magnets through substitution on the nitronyl nitroxide radical.

Two one-dimensional nitronyl nitroxide radical (NITR)-bridged lanthanide chain compounds, namely [Tb(hfac)3(NIT-4-ThienPh)]n (1) and [Tb(hfac)3(NIT-5-ThienPh)]n (2), where hfac = hexafluoroacetylacetonate, NIT-4-ThienPh = 2-(4'-phenyl-2'-thienyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide, and NIT-5-ThienPh = 2-(5'-phenyl-2'-thienyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide, were obtained with different NITRs. Alternating-current magnetic susceptibility studies show that both the compounds are single-chain magnets, while a minor change of the site of the phenyl substituent on the NITR significantly influences the magnetization dynamics. The effective magnetization reversal barrier of 1 (53 cm-1) is more than two times higher than that of 2 (20 cm-1) and the coercive field of 1 is also much higher than that of 2 because of minor changes in the local coordination symmetry of the TbIII centers and the magnetic interactions between the spin carriers along the chain induced by substitution on the radical ligand.

Elevated triglycerides rather than other lipid parameters are associated with increased urinary albumin to creatinine ratio in the general population of China: a report from the REACTION study.

BACKGROUND: Dyslipidaemia has always been regarded as the cornerstone of arteriosclerosis and is related to the pathogenesis of renal insufficiency. However, it is unclear which routinely available lipid parameter is related to urinary albumin to creatinine ratio (UACR). The purpose of this study was to examine the lipid abnormalities associated with UACR in the general population in China. METHODS: The present study was nested in an ongoing Risk Evaluation of cAncers in Chinese diabetic Individuals: A lONgitudinal (REACTION) study, which was designed to demonstrate the association of abnormal glucose metabolism with the risk of cancer in the Chinese population. This cross-sectional study included 34, 569 subjects (11, 390 males and 23, 179 females) from 8 different regional community cohorts, with an average age of 57.9 years. The UACR data were divided into the < 25% group, the 25-49% group, the 50-74% group, and the ≥ 75% group according to the quartile division of the centre where the subjects visited. The lipid classes were defined according to the guidelines for the prevention and treatment of dyslipidaemia in Chinese adults. Multiple logistic regression analysis was used to evaluate the association of the lipid parameters and UACR. RESULTS: Multivariable regression analysis revealed that compared with the other lipid parameters, triglycerides (TG) showed an adjusted odds ratio that was significant in model 1-4. This relationship was attenuated after adjusting for Haemoglobin A1c (HbA1c) and blood pressure (BP), but TG ≥ 2.3 mmol/L was still significantly associated with UACR in total subjects and in both men and women (OR: 1.131, 95% CI 1.065-1.203, P < 0.001 in total subjects; OR: 1.134, 95% CI 1.022-1.258, P = 0.017 in men; OR: 1.129, 95% CI 1.046-1.219, P = 0.002 in women). In the stratified analysis, elevated TG was significantly associated with increased urinary albumin in subjects with eGFR ≥ 90 mL/min per 1.73 m2, 5.6 ≤ FBG < 7.0 or 7.8 ≤ PBG < 11.1 mmol/L, 24 ≤ BMI < 28 kg/m2, 120 ≤ SBP < 140 and/or 80 ≤ DBP < 90 mmHg. CONCLUSIONS: We conclude that high TG levels rather than total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or non-high-density lipoprotein cholesterol levels are associated with UACR in the general population in China.